bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2024–10–06
74 papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño
  1. Mechanisms of Senescence and Anti-Senescence Strategies in the Skin.
  2. High-dimensional Ageome Representations of Biological Aging across Functional Modules.
  3. Targeting senescent cells in aging and COVID-19: from cellular mechanisms to therapeutic opportunities.
  4. Cellular stress and epigenetic regulation in adult stem cells.
  5. Characterization of Age-Dependent Changes in Skeletal Muscle Repair and Regeneration Using a Mouse Model of Acute Muscle Injury.
  6. Searching for Beauty and Health: Aging in Women, Nutrition, and the Secret in Telomeres.
  7. From silence to symphony: transcriptional repression and recovery in response to DNA damage.
  8. Cellular Senescence: The Driving Force of Musculoskeletal Diseases.
  9. Effects and Mechanisms of Lutein on Aging and Age-Related Diseases.
  10. Bioengineered yeast for preventing age-related diseases.
  11. Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases.
  12. Integrating Machine Learning with Multi-Omics Technologies in Geroscience: Towards Personalized Medicine.
  13. Challenging Sarcopenia: Exploring AdipoRon in Aging Skeletal Muscle as a Healthspan-Extending Shield.
  14. Bats as instructive animal models for studying longevity and aging.
  15. Senolytic effect of triterpenoid complex from Ganoderma lucidum on adriamycin-induced senescent human hepatocellular carcinoma cells model in vitro and in vivo.
  16. Matrix stiffness regulates mitochondria-lysosome contacts to modulate the mitochondrial network, alleviate the senescence of MSCs.
  17. TERRA long noncoding RNA: At the interphase of telomere damage, rescue and signaling.
  18. A Two-Photon-Active Zr-Based Metal-Organic Framework-Based Orthogonal Nanoprobe for Recognition of Cellular Senescence.
  19. The Interstitial Gland as a Source of Pro- or Anti-Senescent Cells during Chinchilla Rabbit Ovarian Aging.
  20. Long-term food supplementation with sweet basil (Ocimum basilicum L.) prevents age-associated cognitive decline in female mice.
  21. Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome.
  22. Monoallelic loss of RB1 enhances osteogenic differentiation and delays DNA repair without inducing tumorigenicity.
  23. Role of Phytochemicals in Treatment of Aging and Cancer: Focus on Mechanism of FOXO3 Activation.
  24. β-asarone Protects Against Age-related Motor Decline via Activation of SKN-1/Nrf2 and Subsequent Induction of GST-4.
  25. Healthy Aging at Moderate Altitudes: Hypoxia and Hormesis.
  26. Pro-inflammatory cytokine 11 plays a pivotal role in inflammaging-associated pathologies.
  27. Therapeutic targeting of senescent cells in the CNS.
  28. Associations of healthy eating patterns with biological aging: national health and nutrition examination survey (NHANES) 1999-2018.
  29. p21 Regulates Wnt-Notch balance via DREAM/MMB/Rb-E2F1 and maintains intestinal stem cell homeostasis.
  30. Editorial: New basic and translational perspectives on skin repair.
  31. CRISPR helps brain stem cells regain youth in mice.
  32. Nuclear envelope budding inhibition slows down progerin-induced aging process.
  33. Pulsed Electromagnetic Field (PEMF) stimulation as an adjunct to exercise: a brief review.
  34. Ultraviolet Light Causes Skin Cell Senescence: From Mechanism to Prevention Principle.
  35. Investigating the Effects of Chelidonic Acid on Oxidative Stress-Induced Premature Cellular Senescence in Human Skin Fibroblast Cells.
  36. Balancing the Oral-Gut-Brain Axis with Diet.
  37. Telomere Length Measurement in Human Tissue Sections by Quantitative Fluorescence In Situ Hybridization (Q-FISH).
  38. Nicotinamide mononucleotide supplementation rescues mitochondrial and energy metabolism functions and ameliorates inflammatory states in the ovaries of aging mice.
  39. A simple cell proliferation assay and the inflammatory protein content show significant differences in human plasmas from young and old subjects.
  40. Genetic origins, regulators, and biomarkers of cellular senescence.
  41. Modulating DNA Polα Enhances Cell Reprogramming Across Species.
  42. Inhibition of MAT2A Impairs Skeletal Muscle Repair Function.
  43. Exploring the Relationships between Lifestyle Patterns and Epigenetic Biological Age Measures in Men.
  44. Epitranscriptome in action: RNA modifications in the DNA damage response.
  45. Development of a CRISPR/Cas12a-facilitated fluorescent aptasensor for sensitive detection of small molecules.
  46. Unmodulated 40 Hz Stimulation as a Therapeutic Strategy for Aging: Improvements in Metabolism, Frailty, and Cognitive Function in Senescence-Accelerated Prone 10 Mice.
  47. Antioxidant Peptides and Protein Hydrolysates from Tilapia: Cellular and In Vivo Evidences for Human Health Benefits.
  48. BayesAge 2.0: A Maximum Likelihood Algorithm to Predict Transcriptomic Age.
  49. Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells.
  50. Quiescence and aging of melanocyte stem cells and a novel association with programmed death-ligand 1.
  51. Filbertone Reduces Senescence in C2C12 Myotubes Treated with Doxorubicin or H2O2 through MuRF1 and Myogenin.
  52. Development and clinical application of bioelectrical impedance analysis method for body composition assessment.
  53. Effect of polydatin on the viability and odontogenic differentiation of human dental pulp stem cells: An in-vitro study.
  54. Senescence Rejuvenation through Reduction in Mitochondrial Reactive Oxygen Species Generation by Polygonum cuspidatum Extract: In Vitro Evidence.
  55. DNA-sensing pathways in health, autoinflammatory and autoimmune diseases.
  56. Efficacy of an Innovative Poly-Component Formulation in Counteracting Human Dermal Fibroblast Aging by Influencing Oxidative and Inflammatory Pathways.
  57. Gene co-expression networks reveal sex-biased differences in musculoskeletal ageing.
  58. Curcumol derivatives exhibit ameliorating effects on lipopolysaccharide-induced acute lung injury: Synthesis, biological evaluation, structure-activity relationship and action mechanism.
  59. A Haloarchaeal Transcriptional Regulator That Represses the Expression of CRISPR-Associated Genes.
  60. Berberine extends healthspan and delays neurodegenerative diseases in Caenorhabditis elegans through ROS-dependent PMK-1/SKN-1 activation.
  61. Pharmacology of Aging: Drosophila as a Tool to Validate Drug Targets for Healthy Lifespan.
  62. Gene therapy for chronic pain management.
  63. CoGTEx: Unscaled system-level coexpression estimation from GTEx data forecast novel functional gene partners.
  64. Role of Oxidative Stress Signaling, Nrf2, on Survival and Stemness of Human Adipose-Derived Stem Cells Exposed to X-rays, Protons and Carbon Ions.
  65. Elucidating the effective age for dietary restriction and the key metabolites involved.
  66. CRISPR/Cas: a powerful tool for designing and improving oil crops.
  67. Human Salivary Histatin 1 Regulating IP3R1/GRP75/VDAC1 Mediated Mitochondrial-Associated Endoplasmic Reticulum Membranes (MAMs) Inhibits Cell Senescence For Diabetic Wound Repair.
  68. N 2-Alkyl-dG lesions elicit R-loop accumulation in the genome.
  69. Involvement of Aryl Hydrocarbon Receptor in Longevity and Healthspan: Insights from Humans, Mice, and C. elegans.
  70. Virgin coconut oil mitigates ageing-associated oxidative stress and dyslipidaemia in male Wistar rats.
  71. Microglial senescence in neurodegeneration: Insights, implications, and therapeutic opportunities.
  72. Effect of Chronic Tibolone Administration on Memory and Choline Acetyltransferase and Tryptophan Hydroxylase Content in Aging Mice.
  73. Particulate Matter and Its Molecular Effects on Skin: Implications for Various Skin Diseases.
  74. Drug-Loaded Mesoporous Polydopamine Nanoparticles in Chitosan Hydrogels Enable Myocardial Infarction Repair through ROS Scavenging and Inhibition of Apoptosis.
  1. Biology (Basel). 2024 Aug 23. pii: 647. [Epub ahead of print]13(9):
    Mechanisms of Senescence and Anti-Senescence Strategies in the Skin.
    Evangelia Konstantinou, Eliane Longange, Gürkan Kaya.
      The skin is the layer of tissue that covers the largest part of the body in vertebrates, and its main function is to act as a protective barrier against external environmental factors, such as microorganisms, ultraviolet light and mechanical damage. Due to its important function, investigating the factors that lead to skin aging and age-related diseases, as well as understanding the biology of this process, is of high importance. Indeed, it has been reported that several external and internal stressors contribute to skin aging, similar to the aging of other tissues. Moreover, during aging, senescent cells accumulate in the skin and express senescence-associated factors, which act in a paracrine manner on neighboring healthy cells and tissues. In this review, we will present the factors that lead to skin aging and cellular senescence, as well as ways to study senescence in vitro and in vivo. We will further discuss the adverse effects of the accumulation of chronic senescent cells and therapeutic agents and tools to selectively target and eliminate them.
    Keywords:  SASP; cellular senescence; p16INK4a; senolytics; senomorphics; senotherapy; skin aging
    DOI:  https://doi.org/10.3390/biology13090647
  2. bioRxiv. 2024 Sep 21. pii: 2024.09.17.613599. [Epub ahead of print]
    High-dimensional Ageome Representations of Biological Aging across Functional Modules.
    Kejun Ying, Alexander Tyshkovskiy, Qingwen Chen, Eric Latorre-Crespo, Bohan Zhang, Hanna Liu, Benyamin Matei-Dediu, Jesse R Poganik, Mahdi Moqri, Kristina Kirschne, Jessica Lasky-Su, Vadim N Gladyshev.
      The aging process involves numerous molecular changes that lead to functional decline and increased disease and mortality risk. While epigenetic aging clocks have shown accuracy in predicting biological age, they typically provide single estimates for the samples and lack mechanistic insights. In this study, we challenge the paradigm that aging can be sufficiently described with a single biological age estimate. We describe Ageome, a computational framework for measuring the epigenetic age of thousands of molecular pathways simultaneously in mice and humans. Ageome is based on the premise that an organism's overall biological age can be approximated by the collective ages of its functional modules, which may age at different rates and have different biological ages. We show that, unlike conventional clocks, Ageome provides a high-dimensional representation of biological aging across cellular functions, enabling comprehensive assessment of aging dynamics within an individual, in a population, and across species. Application of Ageome to longevity intervention models revealed distinct patterns of pathway-specific age deceleration. Notably, cell reprogramming, while rejuvenating cells, also accelerated aging of some functional modules. When applied to human cohorts, Ageome demonstrated heterogeneity in predictive power for mortality risk, and some modules showed better performance in predicting the onset of age-related diseases, especially cancer, compared to existing clocks. Together, the Ageome framework offers a comprehensive and interpretable approach for assessing aging, providing insights into mechanisms and targets for intervention.
    DOI:  https://doi.org/10.1101/2024.09.17.613599
  3. Cell Regen. 2024 Oct 02. 13(1): 20
    Targeting senescent cells in aging and COVID-19: from cellular mechanisms to therapeutic opportunities.
    Yuan Yu, Kaixuan Lin, Haoyu Wu, Mingli Hu, Xuejie Yang, Jie Wang, Johannes Grillari, Jiekai Chen.
      The COVID-19 pandemic has caused a global health crisis and significant social economic burden. While most individuals experience mild or non-specific symptoms, elderly individuals are at a higher risk of developing severe symptoms and life-threatening complications. Exploring the key factors associated with clinical severity highlights that key characteristics of aging, such as cellular senescence, immune dysregulation, metabolic alterations, and impaired regenerative potential, contribute to disruption of tissue homeostasis of the lung and worse clinical outcome. Senolytic and senomorphic drugs, which are anti-aging treatments designed to eliminate senescent cells or decrease the associated phenotypes, have shown promise in alleviating age-related dysfunctions and offer a novel approach to treating diseases that share certain aspects of underlying mechanisms with aging, including COVID-19. This review summarizes the current understanding of aging in COVID-19 progression, and highlights recent findings on anti-aging drugs that could be repurposed for COVID-19 treatment to complement existing therapies.
    Keywords:  Aging; Anti-aging Therapies; COVID-19; Cellular Senescence
    DOI:  https://doi.org/10.1186/s13619-024-00201-1
  4. Life Sci Alliance. 2024 Dec;pii: e202302083. [Epub ahead of print]7(12):
    Cellular stress and epigenetic regulation in adult stem cells.
    Joey Llewellyn, Rithvik Baratam, Luka Culig, Isabel Beerman.
      Stem cells are a unique class of cells that possess the ability to differentiate and self-renew, enabling them to repair and replenish tissues. To protect and maintain the potential of stem cells, the cells and the environment surrounding these cells (stem cell niche) are highly responsive and tightly regulated. However, various stresses can affect the stem cells and their niches. These stresses are both systemic and cellular and can arise from intrinsic or extrinsic factors which would have strong implications on overall aging and certain disease states. Therefore, understanding the breadth of drivers, namely epigenetic alterations, involved in cellular stress is important for the development of interventions aimed at maintaining healthy stem cells and tissue homeostasis. In this review, we summarize published findings of epigenetic responses to replicative, oxidative, mechanical, and inflammatory stress on various types of adult stem cells.
    DOI:  https://doi.org/10.26508/lsa.202302083
  5. Methods Mol Biol. 2025 ;2857 169-180
    Characterization of Age-Dependent Changes in Skeletal Muscle Repair and Regeneration Using a Mouse Model of Acute Muscle Injury.
    Faisal J Alibhai, Stephanie W Tobin.
      Acute skeletal muscle injury initiates a process of necrosis, debris clearance, and ultimately tissue regeneration via myogenesis. While skeletal muscle stem cells (MuSCs) are responsible for populating the proliferative myogenic progenitor pool to fuel muscle repair, recruited and resident immune cells have a central role in the regulation of muscle regeneration via the execution of phagocytosis and release of soluble factors that act directly on MuSCs to regulate myogenic differentiation. Therefore, the timing of MuSC proliferation and differentiation is closely linked to the populations and behaviors of immune cells present within skeletal muscle. This has important implications for aging and muscle repair, as systemic changes in immune system function contribute to a decline in muscle regenerative capacity. Here, we present adapted protocols for the isolation of mononuclear cells from skeletal muscles for the quantification of immune cell populations using flow cytometry. We also describe a cardiotoxin skeletal muscle injury protocol and detail the expected outcomes including immune cell infiltration to the injured sites and formation of new myocytes. As immune cell function is substantially influenced by aging, we extend these approaches and outcomes to aged mice.
    Keywords:  Aging; Flow cytometry; Inflammation; Muscle regeneration
    DOI:  https://doi.org/10.1007/978-1-0716-4128-6_16
  6. Nutrients. 2024 Sep 15. pii: 3111. [Epub ahead of print]16(18):
    Searching for Beauty and Health: Aging in Women, Nutrition, and the Secret in Telomeres.
    Virginia Boccardi, Joanna Polom.
      Women typically outlive men, yet they often experience greater frailty and a higher incidence of chronic diseases as they age. By exploring the biological foundations of aging, with a particular focus on telomere dynamics, this manuscript aims to describe how dietary and lifestyle choices can significantly influence the aging process. The review comprehensively examines current research, underscoring the power of nutrition to counteract age-related changes, support healthy aging, and maintain vitality and beauty in women. The exploration of telomeres-the protective caps at the ends of chromosomes-reveals how they serve as markers of cellular aging and are potential targets for interventions aimed at enhancing women's longevity and quality of life. This study also emphasizes the importance of sex-specific approaches and precision medicine in understanding the unique health challenges women face as they age. By proposing targeted strategies, the review seeks to address these challenges, offering insights into preventive measures that can foster resilience, promote well-being, and extend healthy life expectancy in women. Ultimately, this work provides a sophisticated understanding of the aging process in women, highlighting the pivotal role of tailored interventions in preserving both health and beauty.
    Keywords:  aging; beauty; nutrition; sex; telomere; women
    DOI:  https://doi.org/10.3390/nu16183111
  7. Transcription. 2024 Oct 01. 1-15
    From silence to symphony: transcriptional repression and recovery in response to DNA damage.
    Kamal Ajit, Monika Gullerova.
      Genotoxic stress resulting from DNA damage is resolved through a signaling cascade known as the DNA Damage Response (DDR). The repair of damaged DNA is essential for cell survival, often requiring the DDR to attenuate other cellular processes such as the cell cycle, DNA replication, and transcription of genes not involved in DDR. The complex relationship between DDR and transcription has only recently been investigated. Transcription can facilitate the DDR in response to double-strand breaks (DSBs) and stimulate nucleotide excision repair (NER). However, transcription may need to be reduced to prevent potential interference with the repair machinery. In this review, we discuss various mechanisms that regulate transcription repression in response to different types of DNA damage, categorizing them by their range and duration of effect. Finally, we explore various models of transcription recovery following DNA damage-induced repression.
    Keywords:  DNA damage; RNA polymerase II; re-activation; repression; transcription
    DOI:  https://doi.org/10.1080/21541264.2024.2406717
  8. Biomedicines. 2024 Aug 26. pii: 1948. [Epub ahead of print]12(9):
    Cellular Senescence: The Driving Force of Musculoskeletal Diseases.
    Angela Falvino, Beatrice Gasperini, Ida Cariati, Roberto Bonanni, Angela Chiavoghilefu, Elena Gasbarra, Annalisa Botta, Virginia Tancredi, Umberto Tarantino.
      The aging of the world population is closely associated with an increased prevalence of musculoskeletal disorders, such as osteoporosis, sarcopenia, and osteoarthritis, due to common genetic, endocrine, and mechanical risk factors. These conditions are characterized by degeneration of bone, muscle, and cartilage tissue, resulting in an increased risk of fractures and reduced mobility. Importantly, a crucial role in the pathophysiology of these diseases has been proposed for cellular senescence, a state of irreversible cell cycle arrest induced by factors such as DNA damage, telomere shortening, and mitochondrial dysfunction. In addition, senescent cells secrete pro-inflammatory molecules, called senescence-associated secretory phenotype (SASP), which can alter tissue homeostasis and promote disease progression. Undoubtedly, targeting senescent cells and their secretory profiles could promote the development of integrated strategies, including regular exercise and a balanced diet or the use of senolytics and senomorphs, to improve the quality of life of the aging population. Therefore, our review aimed to highlight the role of cellular senescence in age-related musculoskeletal diseases, summarizing the main underlying mechanisms and potential anti-senescence strategies for the treatment of osteoporosis, sarcopenia, and osteoarthritis.
    Keywords:  SASP; cellular senescence; exercise; musculoskeletal diseases; nutrition; osteoarthritis; osteoporosis; physiology; prevention; sarcopenia
    DOI:  https://doi.org/10.3390/biomedicines12091948
  9. Antioxidants (Basel). 2024 Sep 14. pii: 1114. [Epub ahead of print]13(9):
    Effects and Mechanisms of Lutein on Aging and Age-Related Diseases.
    Jialu Ye, Jin Cheng, Ruogu Xiong, Haoqi Chen, Siyu Huang, Huabin Li, Jinzhu Pang, Xuguang Zhang, Huilian Zhu.
      Aging and age-related diseases are serious public health issues that are receiving growing attention from researchers. Lutein has a critical function in the prevention and management of these issues. Possible mechanisms mainly include suppressing inflammation and oxidative stress, regulating cell activity, and modulating the levels of toxic substances. In this narrative review paper, we sum up the most current developments in the study of the effects of lutein on aging and five age-related diseases (age-related macular degeneration, cataracts, Alzheimer's disease, Parkinson's disease, and osteoporosis), and fundamental mechanisms are reviewed. The bioavailability of lutein and the strategies to improve its bioavailability are discussed. This piece of work can bring a clearer comprehension of the protective effects of lutein against aging and age-related diseases and can be also helpful for developing lutein as functional food and dietary supplements for these age-related diseases.
    Keywords:  Alzheimer’s disease; Parkinson’s disease; age-related diseases; age-related macular degeneration; aging; cataract; lutein; osteoporosis
    DOI:  https://doi.org/10.3390/antiox13091114
  10. Trends Biotechnol. 2024 Oct 01. pii: S0167-7799(24)00239-7. [Epub ahead of print]
    Bioengineered yeast for preventing age-related diseases.
    Olga Sofianovich, Kate Willis-Urena, Yueming Dong, Codruta Ignea.
      The aging process entails a multifaceted decline in the capacity to restore homeostasis in response to stress. A prevalent characteristic of many age-related diseases is the presence of low-grade chronic inflammation, a risk factor contributing significantly to morbidity and mortality in the elderly population. Specific lifestyle interventions, such as regular physical activity, targeted diet, and supplementation, can delay the accumulation of chronic age-associated conditions by mitigating inflammation processes. Bioengineered yeast-producing compounds with distinctive bioactivities, including anti-inflammatory properties, have the potential to provide rich dietary alternatives for the prevention of age-related diseases. This review highlights recent achievements in engineering effective yeast platforms, namely Saccharomyces cerevisiae and Yarrowia lipolytica, that hold promise in retarding the onset of aging and age-related ailments.
    Keywords:  age-related diseases; bioactive compounds; biosynthetic pathways; metabolic engineering; synthetic biology; yeast cell factories
    DOI:  https://doi.org/10.1016/j.tibtech.2024.08.011
  11. Nat Rev Mol Cell Biol. 2024 Oct 03.
    Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases.
    Zeming Wu, Jing Qu, Guang-Hui Liu.
      Ageing is a complex biological process in which a gradual decline in physiological fitness increases susceptibility to diseases such as neurodegenerative disorders and cancer. Cellular senescence, a state of irreversible cell-growth arrest accompanied by functional deterioration, has emerged as a pivotal driver of ageing. In this Review, we discuss how heterochromatin loss, telomere attrition and DNA damage contribute to cellular senescence, ageing and age-related diseases by eliciting genome instability, innate immunity and inflammation. We also discuss how emerging therapeutic strategies could restore heterochromatin stability, maintain telomere integrity and boost the DNA repair capacity, and thus counteract cellular senescence and ageing-associated pathologies. Finally, we outline current research challenges and future directions aimed at better comprehending and delaying ageing.
    DOI:  https://doi.org/10.1038/s41580-024-00775-3
  12. J Pers Med. 2024 Aug 31. pii: 931. [Epub ahead of print]14(9):
    Integrating Machine Learning with Multi-Omics Technologies in Geroscience: Towards Personalized Medicine.
    Nikolaos Theodorakis, Georgios Feretzakis, Lazaros Tzelves, Evgenia Paxinou, Christos Hitas, Georgia Vamvakou, Vassilios S Verykios, Maria Nikolaou.
      Aging is a fundamental biological process characterized by a progressive decline in physiological functions and an increased susceptibility to diseases. Understanding aging at the molecular level is crucial for developing interventions that could delay or reverse its effects. This review explores the integration of machine learning (ML) with multi-omics technologies-including genomics, transcriptomics, epigenomics, proteomics, and metabolomics-in studying the molecular hallmarks of aging to develop personalized medicine interventions. These hallmarks include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. Using ML to analyze big and complex datasets helps uncover detailed molecular interactions and pathways that play a role in aging. The advances of ML can facilitate the discovery of biomarkers and therapeutic targets, offering insights into personalized anti-aging strategies. With these developments, the future points toward a better understanding of the aging process, aiming ultimately to promote healthy aging and extend life expectancy.
    Keywords:  aging research; geroscience; hallmarks of aging; machine learning; multi-omics technologies; personalized medicine
    DOI:  https://doi.org/10.3390/jpm14090931
  13. Antioxidants (Basel). 2024 Sep 03. pii: 1073. [Epub ahead of print]13(9):
    Challenging Sarcopenia: Exploring AdipoRon in Aging Skeletal Muscle as a Healthspan-Extending Shield.
    Camille M Selvais, Maria A Davis-López de Carrizosa, Romain Versele, Nicolas Dubuisson, Laurence Noel, Sonia M Brichard, Michel Abou-Samra.
      Sarcopenia, characterized by loss of muscle mass, quality, and function, poses significant risks in aging. We previously demonstrated that long-term treatment with AdipoRon (AR), an adiponectin receptor agonist, alleviated myosteatosis and muscle degeneration in middle-aged obese mice. This study aimed to determine if a shorter AR treatment could effectively offset sarcopenia in older mice. Two groups of old mice (20-23 months) were studied, one untreated (O) and one orally-treated with AR (O-AR) at 50 mg/kg/day for three months, compared with control 3-month-old young mice (Y) or 10-month-old young-adult mice (C-10). Results showed that AR remarkably inversed the loss of muscle mass by restoring the sarcopenia index and fiber count, which were greatly diminished with age. Additionally, AR successfully saved muscle quality of O mice by halving the accumulation of tubular aggregates and aberrant mitochondria, through AMPK pathway activation and enhanced autophagy. AR also bolstered muscle function by rescuing mitochondrial activity and improving exercise endurance. Finally, AR markedly curbed muscle fibrosis and mitigated local/systemic inflammation. Thus, a late three-month AR treatment successfully opposed sarcopenia and counteracted various hallmarks of aging, suggesting AR as a promising anti-aging therapy for skeletal muscles, potentially extending healthspan.
    Keywords:  AMPK; abnormal mitochondria; adiponectin; adiponectin agonist; autophagy; sarcopenia; tubular aggregates
    DOI:  https://doi.org/10.3390/antiox13091073
  14. Ann N Y Acad Sci. 2024 Oct 04.
    Bats as instructive animal models for studying longevity and aging.
    Lisa Noelle Cooper, Mohammad Y Ansari, Grace Capshaw, Alex Galazyuk, Amanda M Lauer, Cynthia F Moss, Karen E Sears, Mark Stewart, Emma C Teeling, Gerald S Wilkinson, Rachel C Wilson, Thomas P Zwaka, Rena Orman.
      Bats (order Chiroptera) are emerging as instructive animal models for aging studies. Unlike some common laboratory species, they meet a central criterion for aging studies: they live for a long time in the wild or in captivity, for 20, 30, and even >40 years. Healthy aging (i.e., healthspan) in bats has drawn attention to their potential to improve the lives of aging humans due to bat imperviousness to viral infections, apparent low rate of tumorigenesis, and unique ability to repair DNA. At the same time, bat longevity also permits the accumulation of age-associated systemic pathologies that can be examined in detail and manipulated, especially in captive animals. Research has uncovered additional and critical advantages of bats. In multiple ways, bats are better analogs to humans than are rodents. In this review, we highlight eight diverse areas of bat research with relevance to aging: genome sequencing, telomeres, and DNA repair; immunity and inflammation; hearing; menstruation and menopause; skeletal system and fragility; neurobiology and neurodegeneration; stem cells; and senescence and mortality. These examples demonstrate the broad relevance of the bat as an animal model and point to directions that are particularly important for human aging studies.
    Keywords:  Chiroptera; hearing; immunity; lifespan; neural system; reproductive physiology; skeletal system
    DOI:  https://doi.org/10.1111/nyas.15233
  15. Front Pharmacol. 2024 ;15 1422363
    Senolytic effect of triterpenoid complex from Ganoderma lucidum on adriamycin-induced senescent human hepatocellular carcinoma cells model in vitro and in vivo.
    Ahmed Attia Ahmed Abdelmoaty, Jing Chen, Kun Zhang, Changhui Wu, Ye Li, Peng Li, Jianhua Xu.
       Background: Ganoderma lucidum (G. lucidum) is a famous medicinal mushroom that has been reported to prevent and treat a variety of diseases. Different extractions from G. lucidum have been used to manage age-related diseases, including cancer. Nevertheless, the senolytic activity of G. lucidum against senescent cancer cells has not been investigated. Although cellular senescence causes tumor growth inhibition, senescent cells promote the growth of the neighboring tumor cells through paracrine effects. Therefore, the elimination of senescent cells is a new strategy for cancer treatment.
    Methods: In this study, senescence was triggered in HCC cells by the chemotherapeutic agent Adriamycin (ADR), and subsequently, cells were treated with TC to assess its senolytic activity.
    Results: We found for the first time that the triterpenoid complex (TC) from G. lucidum had senolytic effect, which could selectively eliminate adriamycin (ADR)-induced senescent cells (SCs) of hepatocellular carcinoma (HCC) cells via caspase-dependent and mitochondrial pathways-mediated apoptosis and reduce the levels of senescence markers, thereby inhibiting the progression of cancers caused by SCs. TC could block autophagy at the late stage in SCs, resulting in a significant activation of TC-induced apoptosis. Furthermore, TC inhibited the senescence-associated secretory phenotype (SASP) in SCs through the inhibition of NF-κB, TFEB, P38, ERK, and mTOR signaling pathways and reducing the number of SCs. Sequential administration of ADR and TC in vivo significantly reduced tumor growth and reversed the toxicity of ADR.
    Conclusion: A triterpenoid complex isolated from G. lucidum may serve as a novel senolytic agent against SCs, and its combination with chemotherapeutic agents may enhance their antitumor efficacy.
    Keywords:  Ganoderma lucidum; hepatocellular carcinoma; senescence; senolytic agent; triterpenoid complex
    DOI:  https://doi.org/10.3389/fphar.2024.1422363
  16. Cell Prolif. 2024 Oct 01. e13746
    Matrix stiffness regulates mitochondria-lysosome contacts to modulate the mitochondrial network, alleviate the senescence of MSCs.
    Kang Wang, Chingchun Ho, Xiangyu Li, Jianfeng Hou, Qipei Luo, Jiahong Wu, Yuxin Yang, Xinchun Zhang.
      The extracellular microenvironment encompasses the extracellular matrix, neighbouring cells, cytokines, and fluid components. Anomalies in the microenvironment can trigger aging and a decreased differentiation capacity in mesenchymal stem cells (MSCs). MSCs can perceive variations in the firmness of the extracellular matrix and respond by regulating mitochondrial function. Diminished mitochondrial function is intricately linked to cellular aging, and studies have shown that mitochondria-lysosome contacts (M-L contacts) can regulate mitochondrial function to sustain cellular equilibrium. Nonetheless, the influence of M-L contacts on MSC aging under varying matrix stiffness remains unclear. In this study, utilizing single-cell RNA sequencing and atomic force microscopy, we further demonstrate that reduced matrix stiffness in older individuals leads to MSC aging and subsequent decline in osteogenic ability. Mechanistically, augmented M-L contacts under low matrix stiffness exacerbate MSC aging by escalating mitochondrial oxidative stress and peripheral division. Moreover, under soft matrix stiffness, cytoskeleton reorganization facilitates rapid movement of lysosomes. The M-L contacts inhibitor ML282 ameliorates MSC aging by reinstating mitochondrial network and function. Overall, our findings confirm that MSC aging is instigated by disruption of the mitochondrial network and function induced by matrix stiffness, while also elucidating the potential mechanism by which M-L Contact regulates mitochondrial homeostasis. Crucially, this presents promise for cellular anti-aging strategies centred on mitochondria, particularly in the realm of stem cell therapy.
    DOI:  https://doi.org/10.1111/cpr.13746
  17. Curr Opin Cell Biol. 2024 Sep 28. pii: S0955-0674(24)00116-9. [Epub ahead of print]91 102437
    TERRA long noncoding RNA: At the interphase of telomere damage, rescue and signaling.
    Eftychia Kyriacou, Joachim Lingner.
      TERRA long noncoding RNAs play key roles in telomere function and maintenance. They can orchestrate telomeric chromatin remodeling, regulate telomere maintenance by telomerase and homology-directed repair, and they participate in the telomeric DNA damage response. TERRA associates with chromosome ends through base-pairing forming R-loops, which are mediated by the RAD51 DNA recombinase and its partner RAD51AP1. Telomeric R-loops interfere with replication fork progression, stimulating a switch of telomere maintenance from semiconservative DNA replication to homology-directed repair (HDR). The latter mechanism is exploited by a subset of cancer cells that lack telomerase, referred to as ALT. In addition, TERRA stimulates HDR at short telomeres during aging, delaying cellular senescence. During carcinogenesis, when cells with eroded telomeres enter replicative crisis, TERRA acts as a signaling molecule to mediate autophagic cell death.
    DOI:  https://doi.org/10.1016/j.ceb.2024.102437
  18. Anal Chem. 2024 Oct 02.
    A Two-Photon-Active Zr-Based Metal-Organic Framework-Based Orthogonal Nanoprobe for Recognition of Cellular Senescence.
    Cong Wen, Rong Sheng Li, Yan Guan, Xiaoxia Chang, Na Li.
      A luminescent nanoprobe capable of orthogonal sensing of two independent events is highly significant for unbiased disease-related detection such as the detection of senescent cells. Moreover, it is invaluable that the nanoprobe possesses a two-photon excitable characteristic that is highly suitable for imaging living cells and tissues. Herein, we present a two-photon-excitable multiluminescent orthogonal-sensing nanoprobe (OS nanoprobe) capable of detecting both pH elevation and β-galactosidase (β-gal) overexpression in senescent cells. In the design, Zr-based dual-emissive metal-organic frameworks prepared from two mixed amino linkers, referred to as NH2-MU, were used as the component for the ratiometric sensing of pH; additionally, fluorogenic resorufin-β-d-galactopyranoside, linked to the NH2-MU framework, enables β-gal detection. In the OS nanoprobe, the signals for pH and β-gal sensing remain independent while maintaining high colocalization. The two-photon excitable organic linkers of NH2-MU impart the OS nanoprobe with a bioimaging capability, allowing for the differentiation of senescent human foreskin fibroblast (HFF) cells from younger HFF cells or LacZ positive cells with the 800 nm laser excitation. This study marks the first instance of achieving the multiplexed orthogonal fluorescent sensing of cellular senescence using a two-photon excitation strategy, suggesting the potential of using versatile metal-organic framework (MOFs)-based fluorophores to realize the orthogonal multiplexing of disease-related biomarkers through multiphoton excitation.
    DOI:  https://doi.org/10.1021/acs.analchem.4c02758
  19. Int J Mol Sci. 2024 Sep 13. pii: 9906. [Epub ahead of print]25(18):
    The Interstitial Gland as a Source of Pro- or Anti-Senescent Cells during Chinchilla Rabbit Ovarian Aging.
    Verónica Díaz-Hernández, Alejandro Marmolejo-Valencia, César Montiel-De la Cruz, Gabriela Piñón-Zárate, Luis M Montaño, Silvia Ivonne Mora-Herrera, Ivette Caldelas.
      The aging ovary in mammals leads to the reduced production of sex hormones and a deterioration in follicle quality. The interstitial gland originates from the hypertrophy of the theca cells of atretic follicles and represents an accumulative structure of the ovary that may contribute to its aging. Here, reproductive and mature rabbit ovaries are used to determine whether the interstitial gland plays a crucial role in ovarian aging. We demonstrate that, in the mature ovary, interstitial gland cells accumulate lipid droplets and show ultrastructural characteristics of lipophagy. Furthermore, they undergo modifications and present a foamy appearance, do not express the pan-leukocyte CD-45 marker, and express CYP11A1. These cells are the first to present an increase in lipofuscin accumulation. In foamy cells, the expression of p21 remains low, PCNA expression is maintained at mature ages, and their nuclei do not show positivity for H2AX. The interstitial gland shows a significant increase in lipofuscin accumulation compared with the ovaries of younger rabbits, but lipofuscin accumulation remains constant at mature ages. Surprisingly, no accumulation of cells with DNA damage is evident, and an increase in proliferative cells is observed at the age of 36 months. We suggest that the interstitial gland initially uses lipophagy to maintain steroidogenic homeostasis and prevent cellular senescence.
    Keywords:  aging; aging ovary; interstitial gland; lipofuscin; lipophagy; ovary; p21; rabbit; senescent cells
    DOI:  https://doi.org/10.3390/ijms25189906
  20. Nutr Health. 2024 Sep 28. 2601060241281765
    Long-term food supplementation with sweet basil (Ocimum basilicum L.) prevents age-associated cognitive decline in female mice.
    Dâmaris Costa Miranda Pires, Alberto da Silva Moraes.
      Background: Mild cognitive decline, a common issue in aging, affects memory, learning, and attention. Nutrition can influence cognition, and research indicates that Ocimum sp. (holy basil and sweet basil) leaf extracts may enhance cognition in rodents and humans. However, these studies do not address whether these benefits extend to fresh or dry leaves consumed in typical human diets, along with physiological aging. Aim: To investigate the effects of sweet basil supplementation on cognition in mature and aged female mice. Methods: Female C57bl mice were divided into four groups: 8-month-old mature adults and 18-month-old aged adults, each receiving either a control or supplemented diet. The supplemented diet included a mix of standard chow and fresh basil leaves, administered for 2-8 months. Cognitive and behavioral assessments were conducted using the novel object recognition (NOR), Morris water maze (MWM), and elevated plus maze (EPM) tasks, focusing on memory, learning, and anxiety. Results: No cognitive improvement was observed in mature mice. However, aged mice receiving long-term basil supplementation showed enhanced discrimination in NOR and stayed closer to the absent platform in MWM compared to nonsupplemented controls. While aging mice exhibited reduced anxiety-like behavior in EPM, basil supplementation prevented this reduction. Conclusion: Basil supplementation appears beneficial in elderly mice, potentially preventing age-related cognitive decline and behavioral changes. These findings support the benefits of basil consumption in cognition and underscore its potential role in promoting healthy aging. Incorporating basil into the diet at a younger age may preserve memory and mitigate behavioral changes as individuals age.
    Keywords:  Cognitive aging; food supplement; memory and learning test; nutrition; sweet basil
    DOI:  https://doi.org/10.1177/02601060241281765
  21. Geroscience. 2024 Oct 04.
    Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome.
    Martina Vinicki, Tea Pribić, Frano Vučković, Azra Frkatović-Hodžić, Isaac Plaza-Andrades, Francisco Tinahones, Joseph Raffaele, José Carlos Fernández-García, Gordan Lauc.
      With aging, the body's ability to maintain regular functions declines, increasing susceptibility to age-related diseases. Therapeutic interventions targeting the underlying biological changes of aging hold promise for preventing or delaying multiple age-related diseases. Metformin, a drug commonly used for diabetes treatment, has emerged as a potential gerotherapeutic agent due to its established safety record and preclinical and clinical data on its anti-aging effects. Glycosylation, one of the most common and complex co- and post-translational protein modifications, plays a crucial role in regulating protein function and has been linked to aging and various diseases. Changes in immunoglobulin G (IgG) glycosylation patterns have been observed with age, and these alterations may serve as valuable biomarkers for disease predisposition, diagnosis, treatment monitoring, and overall health assessment. In this study, we analyzed the IgG glycosylation patterns of white men from Europe, aged 29-45 years, under treatment with metformin, testosterone, metformin plus testosterone, and placebo (trial registration number NCT02514629, 2013/07/04), and investigated the longitudinal changes in glycosylation over time. We observed statistically significant differences in the IgG glycome composition between participants on testosterone therapy and placebo, with decreased agalactosylation and increased galactosylation and sialylation. However, metformin therapy did not result in statistically significant changes in glycosylation patterns. These findings contribute to our understanding of the impact of therapeutic interventions on IgG glycosylation and confirm the value of IgG glycosylation as a significant biomarker, capable of assessing biological age using the GlycanAge index and providing insight into overall health compared to chronological age.
    Keywords:  Aging; Glycosylation; IgG; Metformin; Testosterone
    DOI:  https://doi.org/10.1007/s11357-024-01349-z
  22. Differentiation. 2024 Sep 26. pii: S0301-4681(24)00075-6. [Epub ahead of print]140 100815
    Monoallelic loss of RB1 enhances osteogenic differentiation and delays DNA repair without inducing tumorigenicity.
    Ambily Vincent, Subramanian Krishnakumar, Sowmya Parameswaran.
      The Retinoblastoma (RB1) gene plays a pivotal role in osteogenic differentiation. Our previous study, employing temporal gene expression analysis using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), revealed the deregulation of osteogenic differentiation in patient-derived heterozygous RB1 mutant orbital adipose-derived mesenchymal stem cells (OAMSCs). The study revealed increased Alizarin Red staining, suggesting heightened mineralization without a corresponding increase in osteogenic lineage-specific gene expression. In this study, we performed high-throughput RNA sequencing on RB1+/+ and RB1+/- patient-derived OAMSCs differentiated towards the osteogenic lineage to investigate the pathways and molecular mechanisms. The pathway analysis revealed significant differences in cell proliferation, DNA repair, osteoblast differentiation, and cancer-related pathways in RB1+/- OAMSC-derived osteocytes. These findings were subsequently validated through functional assays. The study revealed that osteogenic differentiation is increased in RB1+/- cells, along with enhanced proliferation of the osteocytes. There were delayed but persistent DNA repair mechanisms in RB1+/- osteocytes, which were sufficient to maintain genomic integrity, thereby preventing or delaying the onset of tumors. This contrasts with our earlier observation of increased mineralization without corresponding gene expression changes, emphasizing the importance of high-throughput analysis over preselected gene set analysis in comprehending functional assay results.
    Keywords:  DNA repair; Osteogenesis; Proliferation; RB1 mutation; RNA sequencing; Tumorigenesis
    DOI:  https://doi.org/10.1016/j.diff.2024.100815
  23. Antioxidants (Basel). 2024 Sep 11. pii: 1099. [Epub ahead of print]13(9):
    Role of Phytochemicals in Treatment of Aging and Cancer: Focus on Mechanism of FOXO3 Activation.
    See-Hyoung Park.
      There have been many studies reporting that the regular consumption of fruits and vegetables is associated with reduced risks of cancer and age-related chronic diseases. Recent studies have demonstrated that reducing reactive oxygen species and inflammation by phytochemicals derived from natural sources can extend lifespans in a range of model organisms. Phytochemicals derived from fruits and vegetables have been known to display both preventative and suppressive activities against various types of cancer via in vitro and in vivo research by interfering with cellular processes critical for tumor development. The current challenge lies in creating tailored supplements containing specific phytochemicals for individual needs. Achieving this goal requires a deeper understanding of the molecular mechanisms through which phytochemicals affect human health. In this review, we examine recently (from 2010 to 2024) reported plant extracts and phytochemicals with established anti-aging and anti-cancer effects via the activation of FOXO3 transcriptional factor. Additionally, we provide an overview of the cellular and molecular mechanisms by which these molecules exert their anti-aging and anti-cancer effects in specific model systems. Lastly, we discuss the limitations of the current research approach and outline for potential future directions in this field.
    Keywords:  FOXO3; anti-aging; anti-cancer; phytochemicals; plant extracts
    DOI:  https://doi.org/10.3390/antiox13091099
  24. Pharmacol Res. 2024 Oct 02. pii: S1043-6618(24)00395-5. [Epub ahead of print] 107450
    β-asarone Protects Against Age-related Motor Decline via Activation of SKN-1/Nrf2 and Subsequent Induction of GST-4.
    Ming Lei, Jiayu Wu, Yanheng Tan, Yang Shi, Wuyan Yang, Haijun Tu, Weihong Tan.
      Decelerating motor decline is important for promoting healthy aging in the elderly population. Acorus tatarinowii Schott is a traditional Chinese medicine that contains β-asarone as a pharmacologically active constituent. We found that β-asarone can decelerate motor decline in various age groups of Caenorhabditis elegans, while concurrently prolonging their lifespan and modulating synaptic transmission. To understand the mechanisms of its efficacy in motor improvement, we investigated and discovered that mitochondrial fragmentation, a marker for aging, is delayed after β-asarone treatment. Moreover, their efficacy is blocked by dysfunctional mitochondria. Corresponding to their role in regulating mitochondrial homeostasis, we found that SKN-1/Nrf2 and GST-4 are critical in the β-asarone treatment, and they appear to be activated via the insulin/IGF-1 signaling pathway. Well-developed intestinal microvilli are required for this process. Our study demonstrates the efficacy and mechanism of β-asarone treatment in age-related motor decline, contributing to the discovery of drugs for achieving healthy aging.
    Keywords:  healthy aging; mitochondrial fragmentation; motor decline; synaptic transmission; β-asarone
    DOI:  https://doi.org/10.1016/j.phrs.2024.107450
  25. Gerontology. 2024 Sep 30. 1-9
    Healthy Aging at Moderate Altitudes: Hypoxia and Hormesis.
    Johannes Burtscher, Michele Samaja.
       BACKGROUND: Aging is associated with cellular and tissue responses that collectively lead to functional and structural deterioration of tissues. Poor tissue oxygenation, or hypoxia, is involved in such responses and contributes to aging. Consequently, it could be speculated that living at higher altitude, and therefore in hypoxic conditions, accelerates aging. This assumption is indeed supported by evidence from populations residing at very high altitudes (>3,500 m). In contrast, accumulating evidence suggests that living at moderate altitudes (1,500-2,500 m) is protective rather than injurious, at least for some body systems.
    SUMMARY: In this review, we critically evaluate the hypothesis that the physiological responses to mild hypoxic stress associated to life at moderate altitudes provide protection from many hypoxia-related diseases through hormesis. Hormesis means that a low dose of a stressor (here hypoxia) elicits beneficial outcomes, while a higher dose can be toxic and might explain at least in part the dose-dependent contrasting effects of hypoxia on the aging processes. The lack of well-designed longitudinal studies focusing on the role of the altitude of residence, and difficulties in accounting for potentially confounding factors such as migration, ethnicity/genetics, and socioeconomic and geoclimatic conditions, currently hampers translation of related research into uncontroversial paradigms.
    KEY MESSAGES: Deeper investigations are required to understand the impact of altitude-related hypoxia on age-related diseases and to develop molecular markers of ageing/senescence in humans that are linked to hypoxia. However, the presented emerging evidence supports the view that hypoxia conditioning has the potential to improve life quality and expectancy.
    Keywords:  Age-related diseases; Hypoxia-inducible factor; Inflammation; Mortality; Oxygen
    DOI:  https://doi.org/10.1159/000541216
  26. Aging Cell. 2024 Oct 03. e14360
    Pro-inflammatory cytokine 11 plays a pivotal role in inflammaging-associated pathologies.
    José M Izquierdo.
      Chronic sterile inflammation contributes to aging-associated pathologies/malignancies like cancer and autoimmune disorders. In their recent Nature article, Widjaja et al. established the pro-inflammatory, pro-fibrotic cytokine 11 (IL11) as a regulatory driver/hub of aging-associated inflammation (inflammaging) in mice. Genetic and pharmacological IL11 blockade reduces inflammaging, improving healthspan, lifespan, and longevity in male and female mice, highlighting IL11 as a new inflammatory aging clock and a potential molecular target in inflammaging-associated human degenerative diseases.
    Keywords:  aging; healthspan; immunotherapy; inflammation; interleukin 11; lifespan; longevity
    DOI:  https://doi.org/10.1111/acel.14360
  27. Nat Rev Drug Discov. 2024 Sep 30.
    Therapeutic targeting of senescent cells in the CNS.
    Markus Riessland, Methodios Ximerakis, Andrew A Jarjour, Bin Zhang, Miranda E Orr.
      Senescent cells accumulate throughout the body with advanced age, diseases and chronic conditions. They negatively impact health and function of multiple systems, including the central nervous system (CNS). Therapies that target senescent cells, broadly referred to as senotherapeutics, recently emerged as potentially important treatment strategies for the CNS. Promising therapeutic approaches involve clearing senescent cells by disarming their pro-survival pathways with 'senolytics'; or dampening their toxic senescence-associated secretory phenotype (SASP) using 'senomorphics'. Following the pioneering discovery of first-generation senolytics dasatinib and quercetin, dozens of additional therapies have been identified, and several promising targets are under investigation. Although potentially transformative, senotherapies are still in early stages and require thorough testing to ensure reliable target engagement, specificity, safety and efficacy. The limited brain penetrance and potential toxic side effects of CNS-acting senotherapeutics pose challenges for drug development and translation to the clinic. This Review assesses the potential impact of senotherapeutics for neurological conditions by summarizing preclinical evidence, innovative methods for target and biomarker identification, academic and industry drug development pipelines and progress in clinical trials.
    DOI:  https://doi.org/10.1038/s41573-024-01033-z
  28. Nutr J. 2024 Sep 28. 23(1): 112
    Associations of healthy eating patterns with biological aging: national health and nutrition examination survey (NHANES) 1999-2018.
    Xuanyang Wang, Xuemin Yan, Jia Zhang, Sijia Pan, Ran Li, Licheng Cheng, Xiang Qi, Lin Li, Ying Li.
       BACKGROUND: Healthy dietary patterns have been negatively associated with methylation-based measures of biological age, yet previous investigations have been unable to establish the relationship between them and biological aging assessed through blood chemistry-based clinical biomarkers. We sought to assess the associations of 4 dietary metrics with 4 measures of biological age.
    METHODS: Among 16,666 participants in NHANES 1999-2018, 4 dietary metrics [Dietary inflammatory index (DII), Dietary approaches to stop hypertension index (DASH), Alternate mediterranean diet score (aMED), and Healthy eating index-2015 (HEI-2015)] were calculated through the 'dietaryindex' R package. Twelve blood chemistry parameters were utilized to compute 4 indicators of biological age [homeostatic dysregulation (HD), allostatic load (AL), Klemera-Doubal method (KDM), and phenotypic age (PA)]. Binomial logistic regression models and restricted cubic spline (RCS) regression were employed to evaluate the associations.
    RESULTS: All 4 dietary metrics were significantly associated with biological age acceleration or deceleration. In comparison to the lowest DII, the odds ratios (ORs) for accelerated HD, AL, KDM, and PA were 1.25 (1.08,1.45), 1.29 (1.11,1.50), 1.34 (1.08,1.65), and 1.61 (1.39,1.87) for the highest. The multivariable-adjusted ORs of the highest quartile of DASH, aMED, and HEI-2015 were 0.85 (0.73,0.97), 0.88 (0.74,1.04), and 0.84 (0.74,0.96) for HD, 0.64 (0.54,0.75), 0.61 (0.52,0.72), and 0.70 (0.59,0.82) for AL, 0.68 (0.54,0.85), 0.62 (0.50,0.76), and 0.71 (0.58,0.87) for KDM, and 0.50 (0.42,0.59), 0.64 (0.54,0.76), and 0.51 (0.44,0.58) for PA when compared with the lowest level. The findings were validated by the best-fitting dose-response curves for the associations. Among participants consuming dietary supplements (Pinteraction < 0.05), the positive effects of a healthy dietary pattern on biological aging were more pronounced. Systemic immune inflammation index (SII) and atherogenic index of plasma (AIP) were identified as being involved in and mediating the associations.
    CONCLUSIONS: Biological aging assessed through blood chemistry-based clinical biomarkers is negatively associated with diet quality. The anti-aging benefits of improving the diet may be due to its ability to reduce inflammation and lower blood lipids.
    Keywords:  Biological age; Biological aging; Dietary metrics; Healthy eating patterns; National Health and Nutrition Examination Survey (NHANES)
    DOI:  https://doi.org/10.1186/s12937-024-01017-0
  29. Cell Death Discov. 2024 Sep 28. 10(1): 413
    p21 Regulates Wnt-Notch balance via DREAM/MMB/Rb-E2F1 and maintains intestinal stem cell homeostasis.
    Liangxia Jiang, Jie Tian, Jun Yang, Ronggang Luo, Yongjin Zhang, Chihao Shao, Bing Guo, Xiaoming Wu, Juhua Dan, Ying Luo.
      The crosstalk and balance regulation of Wnt-Notch have been known to be essential for cell fate decision and tissue regeneration, however, how this balance is maintained and how the Wnt-Notch pathways are connected with cell cycle regulation is still not clear. By analyzing the molecular alterations in mouse model with accelerated aging phenotypes due to loss of p21 function in a Werner syndrome background, we observed that Wnt3 and β-Catenin were down-regulated, while Notch1 and Hes1 were up-regulated. This disruption in Wnt-Notch signaling was accompanied by the loss of intestinal stem cell compartment, increase in Bmi1 positive cells, loss of Olfm4/Lgr5 positive cells, and reduced secretory Paneth cells and goblet cells in the intestinal crypts of p21TKO mice. BrdU incorporation, cleaved caspase 3, and Tunel assay results revealed the fast turnover of intestinal epithelia, which may result in abnormal stem cell mobilization and exhaustion of the stem cell reservoir in the intestinal crypts. We further identified shift of DREAM complex towards MMB complex due to the loss of p21 as the cause for faster turnover of intestinal epithelia. Importantly, we identified the E2F1 as the transcriptional regulator for Notch1, which linked the p21-DREAM/MMB/Rb-E2F1 pathway with Wnt-Notch pathway. The overexpression of p21 rescued the DREAM pathway, as well as the imbalance of Wnt-Notch pathway. In summary, our data identify p21 as an important factor in maintaining sequential mobilization, proliferation, and homeostasis of intestinal stem cells.
    DOI:  https://doi.org/10.1038/s41420-024-02192-z
  30. Front Physiol. 2024 ;15 1469900
    Editorial: New basic and translational perspectives on skin repair.
    Yujie Li, Jibin Xia, Yiming Zhang.
      
    Keywords:  SCAR; angiogenesis; cellular senescence; inflammation; skin repair; wound healing
    DOI:  https://doi.org/10.3389/fphys.2024.1469900
  31. Nature. 2024 Oct 02.
    CRISPR helps brain stem cells regain youth in mice.
    Heidi Ledford.
      
    Keywords:  Ageing; Brain; CRISPR-Cas9 genome editing; Stem cells
    DOI:  https://doi.org/10.1038/d41586-024-03177-9
  32. Proc Natl Acad Sci U S A. 2024 Oct 08. 121(41): e2321378121
    Nuclear envelope budding inhibition slows down progerin-induced aging process.
    Xiangyang Wang, Lin Ma, Di Lu, Gan Zhao, He Ren, Qiaoyu Lin, Mingkang Jia, Fan Huang, Shan Wang, Zhe Xu, Zhou Yang, Yan Chu, Zigang Xu, Wei Li, Li Yu, Qing Jiang, Chuanmao Zhang.
      Progerin causes Hutchinson-Gilford progeria syndrome (HGPS), but how progerin accelerates aging is still an interesting question. Here, we provide evidence linking nuclear envelope (NE) budding and accelerated aging. Mechanistically, progerin disrupts nuclear lamina to induce NE budding in concert with lamin A/C, resulting in transport of chromatin into the cytoplasm where it is removed via autophagy, whereas emerin antagonizes this process. Primary cells from both HGPS patients and mouse models express progerin and display NE budding and chromatin loss, and ectopically expressing progerin in cells can mimic this process. More excitingly, we screen a NE budding inhibitor chaetocin by high-throughput screening, which can dramatically sequester progerin from the NE and prevent this NE budding through sustaining ERK1/2 activation. Chaetocin alleviates NE budding-induced chromatin loss and ameliorates HGPS defects in cells and mice and significantly extends lifespan of HGPS mice. Collectively, we propose that progerin-induced NE budding participates in the induction of progeria, highlight the roles of chaetocin and sustained ERK1/2 activation in anti-aging, and provide a distinct avenue for treating HGPS.
    Keywords:  ERK1/2; Hutchinson–Gilford progeria syndrome; NE budding; chromatin loss; progerin
    DOI:  https://doi.org/10.1073/pnas.2321378121
  33. Front Sports Act Living. 2024 ;6 1471087
    Pulsed Electromagnetic Field (PEMF) stimulation as an adjunct to exercise: a brief review.
    Sheyda Ghanbari Ghoshchi, Maria Letizia Petroni, Alessandro Piras, Samuele Maria Marcora, Milena Raffi.
      Pulsed Electromagnetic Field (PEMF) therapy is a non-invasive treatment that utilizes electromagnetic fields to stimulate and promote natural healing processes within the body. PEMF therapy works by emitting low-frequency electromagnetic pulses, which penetrate deep into tissues and cells, enhancing cellular function and health. PEMF applications are vast, ranging from enhancing recovery in athletes to supporting overall well-being in everyday individuals. PEMF therapy is increasingly recognized in the realm of sports and physical activity for its profound benefits in enhancing performance, accelerating recovery, and preventing injuries. By improving circulation, enhancing tissue oxygenation, and promoting the body's natural healing processes, PEMF therapy has become an invaluable tool in sports medicine, contributing to optimized physical health and prolonged athletic careers. In this review, we explore the effects of PEMF on exercise and the underlying physiological mechanisms.
    Keywords:  DOMS; PEMF; athletes; performance; physical activity; physical exercise; recovery; sport
    DOI:  https://doi.org/10.3389/fspor.2024.1471087
  34. Adv Biol (Weinh). 2024 Oct 04. e2400090
    Ultraviolet Light Causes Skin Cell Senescence: From Mechanism to Prevention Principle.
    Shujia Song, Fuxing Li, Bingxiang Zhao, Min Zhou, Xiaobo Wang.
      The skin is an effective protective barrier that significantly protects the body from damage caused by external environmental factors. Furthermore, skin condition significantly affects external beauty. In today's era, which is of material and spiritual prosperity, there is growing attention on skincare and wellness. Ultraviolet radiation is one of the most common external factors that lead to conditions like sunburn, skin cancer, and skin aging. In this review, several mechanisms of UV-induced skin cell senescence are discussed, including DNA damage, oxidative stress, inflammatory response, and mitochondrial dysfunction, which have their own characteristics and mutual effects. As an illustration, mitochondrial dysfunction triggers electron evasion and the generation of more reactive oxygen species, leading to oxidative stress and the activation of the NLRP3 inflammasome, which in turn causes mitochondrial DNA (mt DNA) damage. Based on the current mechanism, suitable prevention and treatment strategies are proposed from sunscreen, dietary, and experimental medications respectively, aimed at slowing down skin cell aging and providing protection from ultraviolet radiation. The effects of ultraviolet rays on skin is summarized, offering insights and directions for future studies on mechanism of skin cell senescence, with an anticipation of discovering more effective prevention and cure methods.
    Keywords:  aging mechanism; preventive measure; skin aging; skin structure; ultraviolet light
    DOI:  https://doi.org/10.1002/adbi.202400090
  35. Life (Basel). 2024 Aug 27. pii: 1070. [Epub ahead of print]14(9):
    Investigating the Effects of Chelidonic Acid on Oxidative Stress-Induced Premature Cellular Senescence in Human Skin Fibroblast Cells.
    Burcu Turkoglu, Banu Mansuroglu.
      This study investigated the effects of chelidonic acid (CA) on hydrogen peroxide (H2O2) induced cellular senescence in human skin fibroblast cells (BJ). Cellular senescence is a critical mechanism that is linked to age-related diseases and chronic conditions. CA, a γ-pyrone compound known for its broad pharmacological activity, was assessed for its potential to mitigate oxidative stress and alter senescence markers. A stress-induced premature senescence (SIPS) model was designed in BJ fibroblast cells using the oxidative stress agent H2O2. After this treatment, cells were treated with CA, and the potential effect of CA on senescence was evaluated using senescence-related β-galactosidase, 4',6-diamino-2-phenylindole (DAPI), acridine-orange staining (AO), comet assay, molecular docking assays, gene expression, and protein analysis. These results demonstrate that CA effectively reduces senescence markers, including senescence-associated β-galactosidase activity, DNA damage, lysosomal activity, and oxidative stress indicators such as malondialdehyde. Molecular docking revealed CA's potential interactions with critical proteins involved in senescence signalling pathways, suggesting mechanisms by which CA may exert its effects. Gene expression and protein analyses corroborated the observed anti-senescent effects, with CA modulating p16, p21, and pRB1 expressions and reducing oxidative stress markers. In conclusion, CA appeared to have senolytic and senomorphic potential in vitro, which could mitigate and reverse SIPS markers in BJ fibroblasts.
    Keywords:  BJ Fibroblasts; H2O2; chelidonic acid; oxidative stress; premature senescence; senescence; senolytic; senomorphic
    DOI:  https://doi.org/10.3390/life14091070
  36. Nutrients. 2024 Sep 22. pii: 3206. [Epub ahead of print]16(18):
    Balancing the Oral-Gut-Brain Axis with Diet.
    Rebecca Kerstens, Yong Zhi Ng, Sven Pettersson, Anusha Jayaraman.
      Background: The oral microbiota is the second largest microbial community in humans. It contributes considerably to microbial diversity and health effects, much like the gut microbiota. Despite physical and chemical barriers separating the oral cavity from the gastrointestinal tract, bidirectional microbial transmission occurs between the two regions, influencing overall host health. Method: This review explores the intricate interplay of the oral-gut-brain axis, highlighting the pivotal role of the oral microbiota in systemic health and ageing, and how it can be influenced by diet. Results: Recent research suggests a relationship between oral diseases, such as periodontitis, and gastrointestinal problems, highlighting the broader significance of the oral-gut axis in systemic diseases, as well as the oral-gut-brain axis in neurological disorders and mental health. Diet influences microbial diversity in the oral cavity and the gut. While certain diets/dietary components improve both gut and oral health, others, such as fermentable carbohydrates, can promote oral pathogens while boosting gut health. Conclusions: Understanding these dynamics is key for promoting a healthy oral-gut-brain axis through dietary interventions that support microbial diversity and mitigate age-related health risks.
    Keywords:  diet; gut microbiota; oral microbiota; oral–gut–brain axis; periodontitis
    DOI:  https://doi.org/10.3390/nu16183206
  37. Methods Mol Biol. 2025 ;2857 9-14
    Telomere Length Measurement in Human Tissue Sections by Quantitative Fluorescence In Situ Hybridization (Q-FISH).
    Keisuke Nonaka, Junko Aida, Yasuko Hasegawa, Tomio Arai, Toshiyuki Ishiwata, Kaiyo Takubo.
      Telomeres in most somatic cells shorten with each cell division, and critically short telomeres lead to cellular dysfunction, cell cycle arrest, and senescence. Thus, telomere shortening is an important hallmark of human cellular senescence. Quantitative fluorescence in situ hybridization (Q-FISH) using formalin-fixed paraffin-embedded (FFPE) tissue sections allows the estimation of telomere lengths in individual cells in histological sections. In our Q-FISH method, fluorescently labelled peptide nucleic acid (PNA) probes are hybridized to telomeric and centromeric sequences in FFPE human tissue sections, and relative telomere lengths (telomere signal intensities relative to centromere signal intensities) are measured. This chapter describes our Q-FISH protocols for assessing relative telomere lengths in FFPE human tissue sections.
    Keywords:  Centromere; FFPE; Formalin-fixed paraffin-embedded; Human tissue; PNA probe; Q-FISH; Quantitative fluorescence in situ hybridization; Relative telomere length; Telomere
    DOI:  https://doi.org/10.1007/978-1-0716-4128-6_2
  38. MedComm (2020). 2024 Oct;5(10): e727
    Nicotinamide mononucleotide supplementation rescues mitochondrial and energy metabolism functions and ameliorates inflammatory states in the ovaries of aging mice.
    Jinghui Liang, Feiling Huang, Xueyu Hao, Peng Zhang, Rong Chen.
      Noninvasive pharmacological strategies like nicotinamide mononucleotide (NMN) supplementation can effectively address age-related ovarian infertility by maintaining or enhancing oocyte quality and quantity. This study revealed that ovarian nicotinamide adenine dinucleotide levels decline with age, but NMN administration significantly restores these levels, preventing ovarian atrophy and enhancing the quality and quantity of ovulated oocytes. Improvements in serum hormone secretion and antioxidant factors, along with decreased expression of proinflammatory factors, were observed. Additionally, a significant increase in the number of ovarian follicles in aging individuals was noted. Scanning electron microscopy data indicated that NMN significantly alters the density and morphology of lipid droplets and mitochondria in granulosa cells, suggesting potential targets and mechanisms. Transcriptomic analysis and validation experiments collectively suggested that the beneficial effects of NMN on aging ovaries are mediated through enhanced mitochondrial function, improved energy metabolism, and reduced inflammation levels. Our results suggest that NMN supplementation could improve the health status of aging ovaries and enhance ovarian reserve, offering new insights into addressing fertility challenges in older women through assisted reproductive technology.
    Keywords:  infertility; nicotinamide adenine dinucleotide (NAD+); nicotinamide mononucleotide; ovarian aging
    DOI:  https://doi.org/10.1002/mco2.727
  39. Front Bioeng Biotechnol. 2024 ;12 1408499
    A simple cell proliferation assay and the inflammatory protein content show significant differences in human plasmas from young and old subjects.
    A Muraglia, O Utyro, M Nardini, M Santolini, D Ceresa, V Agostini, A Nencioni, G Filaci, R Cancedda, M Mastrogiacomo.
      Some studies showed a "rejuvenating" effect of exposing aging tissues to a young environment. In mouse heterochronic parabiosis experiments, in response to young organisms, old animals lived longer than isochrony old age-matched conjoint animals. Comparable "rejuvenating" effects were obtained by injecting young plasma in old mice. This raised great hopes of slowing down the senescence process in humans by the injection of young plasma, as well as to prevent or cure age-related diseases. Some clinical trials are currently being performed or were recently completed. However, these studies are small and of limited duration, and we still lack convincing evidence to support the effectiveness of young plasma injection. It is urgent to perform additional investigations, including the development of an assay to measure the cell proliferation induction capability of different human plasmas, before one can seriously think of a large-scale treatment of humans. We adopted a simple method to measure the potential of different plasmas in supporting cell line proliferation, regardless of the co-presence of a platelet lysate. By comparing plasmas from young and old subjects, we observed a decreased activity in plasmas from old individuals. The young plasma effect may be attributed to specific proteins and growth factors more abundant in younger individuals that could decrease with age. Alternatively, or at the same time, the reduced cell proliferation support could be due to inhibitors present in the old plasma. Studying the different protein content of young and old plasmas was out of the scope of this article. Such differences should be adequately investigated by proteomics using many samples. However, a preliminary study of the different protein content of young and old plasmas was part of the assay validation using a commercially available cytokine array for parallel determination of the relative levels of 105 selected human proteins. We could show the existence of specific differences between young and old plasmas and that plasmas from old individuals presented a higher concentration of "inflammatory" proteins.
    Keywords:  breast cancer cell line MDA; cell proliferation support; fetal foreskin fibroblast cell line HFFF2; rejuvenation; senescence-associated secretory phenotype; young plasma injection
    DOI:  https://doi.org/10.3389/fbioe.2024.1408499
  40. Trends Genet. 2024 Sep 27. pii: S0168-9525(24)00184-7. [Epub ahead of print]
    Genetic origins, regulators, and biomarkers of cellular senescence.
    Grasiela Torres, Ivan A Salladay-Perez, Anika Dhingra, Anthony J Covarrubias.
      This review comprehensively examines the molecular biology and genetic origins of cellular senescence. We focus on various cellular stressors and pathways leading to senescence, including recent advances in the understanding of the genetic influences driving senescence, such as telomere attrition, chemotherapy-induced DNA damage, pathogens, oncogene activation, and cellular and metabolic stress. This review also highlights the complex interplay of various signaling and metabolic pathways involved in cellular senescence and provides insights into potential therapeutic targets for aging-related diseases. Furthermore, this review outlines future research directions to deepen our understanding of senescence biology and develop effective interventions targeting senescent cells (SnCs).
    Keywords:  SASP; aging; cellular senescence
    DOI:  https://doi.org/10.1016/j.tig.2024.08.007
  41. bioRxiv. 2024 Sep 20. pii: 2024.09.19.613993. [Epub ahead of print]
    Modulating DNA Polα Enhances Cell Reprogramming Across Species.
    Rajesh Ranjan, Binbin Ma, Ryan J Gleason, Yijun Liao, Yingshan Bi, Brendon E M Davis, Guanghui Yang, Maggie Clark, Vikrant Mahajan, Madison Condon, Nichole A Broderick, Xin Chen.
      As a fundamental biological process, DNA replication ensures the accurate copying of genetic information. However, the impact of this process on cellular plasticity in multicellular organisms remains elusive. Here, we find that reducing the level or activity of a replication component, DNA Polymerase α (Polα), facilitates cell reprogramming in diverse stem cell systems across species. In Drosophila male and female germline stem cell lineages, reducing Polα levels using heterozygotes significantly enhances fertility of both sexes, promoting reproductivity during aging without compromising their longevity. Consistently, in C. elegans the pola heterozygous hermaphrodites exhibit increased fertility without a reduction in lifespan, suggesting that this phenomenon is conserved. Moreover, in male germline and female intestinal stem cell lineages of Drosophila , polα heterozygotes exhibit increased resistance to tissue damage caused by genetic ablation or pathogen infection, leading to enhanced regeneration and improved survival during post-injury recovery, respectively. Additionally, fine tuning of an inhibitor to modulate Polα activity significantly enhances the efficiency of reprogramming human embryonic fibroblasts into induced pluripotent cells. Together, these findings unveil novel roles of a DNA replication component in regulating cellular reprogramming potential, and thus hold promise for promoting tissue health, facilitating post-injury rehabilitation, and enhancing healthspan.
    DOI:  https://doi.org/10.1101/2024.09.19.613993
  42. Biomolecules. 2024 Sep 02. pii: 1098. [Epub ahead of print]14(9):
    Inhibition of MAT2A Impairs Skeletal Muscle Repair Function.
    Wanli Xiao, Tian-E Huang, Jing Zhou, Benhui Wang, Xiang Wang, Weirong Zeng, Qiquan Wang, Xinqiang Lan, Yang Xiang.
      The regenerative capacity of muscle, which primarily relies on anabolic processes, diminishes with age, thereby reducing the effectiveness of therapeutic interventions aimed at treating age-related muscle atrophy. In this study, we observed a decline in the expression of methionine adenosine transferase 2A (MAT2A), which synthesizes S-adenosylmethionine (SAM), in the muscle tissues of both aged humans and mice. Considering MAT2A's critical role in anabolism, we hypothesized that its reduced expression contributes to the impaired regenerative capacity of aging skeletal muscle. Mimicking this age-related reduction in the MAT2A level, either by reducing gene expression or inhibiting enzymatic activity, led to inhibiting their differentiation into myotubes. In vivo, inhibiting MAT2A activity aggravated BaCl2-induced skeletal muscle damage and decreased the number of satellite cells, whereas supplementation with SAM improved these effects. RNA-sequencing analysis further revealed that the Fas cell surface death receptor (Fas) gene was upregulated in Mat2a-knockdown C2C12 cells. Suppressing MAT2A expression or activity elevated Fas protein levels and increased the proportion of apoptotic cells. Additionally, inhibition of MAT2A expression or activity increased p53 expression. In conclusion, our findings demonstrated that impaired MAT2A expression or activity compromised the regeneration and repair capabilities of skeletal muscle, partially through p53-Fas-mediated apoptosis.
    Keywords:  C2C12; Fas; Mat2a; regeneration; skeletal muscle
    DOI:  https://doi.org/10.3390/biom14091098
  43. Biomedicines. 2024 Sep 02. pii: 1985. [Epub ahead of print]12(9):
    Exploring the Relationships between Lifestyle Patterns and Epigenetic Biological Age Measures in Men.
    Te-Min Ke, Artitaya Lophatananon, Kenneth R Muir.
      DNA methylation, validated as a surrogate for biological age, is a potential tool for predicting future morbidity and mortality outcomes. This study aims to explore how lifestyle patterns are associated with epigenetic changes in British men. Five biological age clocks were utilised to investigate the relationship between these epigenetic markers and lifestyle-related factors in a prospective study involving 221 participants. Spearman's correlation test, Pearson's correlation test, and univariate linear regression were employed for analysis. The results indicate that higher consumption of saturated fat and total daily calories, and a higher body mass index (BMI) are associated with accelerated biological aging. Conversely, higher vitamin D intake and a higher healthy lifestyle index (HLI) are linked to decelerated biological aging. These findings highlight the potential impact of specific lifestyle-related factors on biological aging and can serve as a reference for applying healthy lifestyle improvements in future disease prevention studies.
    Keywords:  DNA methylation; biological age clock; epigenetic biological age; epigenetic markers; healthy lifestyle index (HLI); lifestyle patterns
    DOI:  https://doi.org/10.3390/biomedicines12091985
  44. Mol Cell. 2024 Oct 03. pii: S1097-2765(24)00736-6. [Epub ahead of print]84(19): 3610-3626
    Epitranscriptome in action: RNA modifications in the DNA damage response.
    Blerta Xhemalçe, Kyle M Miller, Natalia Gromak.
      Complex pathways involving the DNA damage response (DDR) contend with cell-intrinsic and -extrinsic sources of DNA damage. DDR mis-regulation results in genome instability that can contribute to aging and diseases including cancer and neurodegeneration. Recent studies have highlighted key roles for several RNA species in the DDR, including short RNAs and RNA/DNA hybrids (R-loops) at DNA break sites, all contributing to efficient DNA repair. RNAs can undergo more than 170 distinct chemical modifications. These RNA modifications have emerged as key orchestrators of the DDR. Here, we highlight the function of enzyme- and non-enzyme-induced RNA modifications in the DDR, with particular emphasis on m6A, m5C, and RNA editing. We also discuss stress-induced RNA damage, including RNA alkylation/oxidation, RNA-protein crosslinks, and UV-induced RNA damage. Uncovering molecular mechanisms that underpin the contribution of RNA modifications to DDR and genome stability will have direct application to disease and approaches for therapeutic intervention.
    Keywords:  DNA damage response; DNA repair; R-loops; RNA alkylation; RNA editing; RNA modifications; RNA oxidation; RNA-protein crosslink; RNA/DNA hybrids; UV-induced RNA damage; hm(5)C; m(5)C; m(6)A
    DOI:  https://doi.org/10.1016/j.molcel.2024.09.003
  45. Int J Biol Macromol. 2024 Sep 26. pii: S0141-8130(24)06850-8. [Epub ahead of print]280(Pt 4): 136041
    Development of a CRISPR/Cas12a-facilitated fluorescent aptasensor for sensitive detection of small molecules.
    Ling Li, Menglei Li, Sai Wang, Yiyang Dong.
      The integration of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated proteins (Cas) exhibits superior performance in biosensor construction. And the distinctive role of aptamers in target recognition has long been a focal point of research. Through the combination of Cas12a with cis-cleavage activity and aptamer with specific recognition, a simple and rapid fluorescent biosensor has been constructed. Interestingly, with modified fluorescent and quenching groups at two ends, aptamers play a dual role: primarily as the elements for target recognition and additionally functioning act as the fluorescent probe for signal output. Coupling with cis-cleavage of Cas12a, the demand of additional signal probes is eliminated, thus simplifying the reaction system and enhancing result accuracy. Taking okadaic acid (OA) as a representative small molecule model to evaluate the sensor's performance, a simple and straightforward detection method was established. Following this, the universality of the constructed fluorescent aptasensor was validated by incorporating an adenosine triphosphate (ATP) aptamer. Consequently, the CRISPR/Cas12a-assisted aptasensor was demonstrated to serve as a versatile detection platform for small molecules in food safety and clinical diagnostics. In the forthcoming research endeavors, it can be further extended for applications in environmental analysis and various other fields.
    Keywords:  CRISPR/Cas12a; Fluorescent aptasensors; Small molecule
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.136041
  46. Biomolecules. 2024 Aug 28. pii: 1079. [Epub ahead of print]14(9):
    Unmodulated 40 Hz Stimulation as a Therapeutic Strategy for Aging: Improvements in Metabolism, Frailty, and Cognitive Function in Senescence-Accelerated Prone 10 Mice.
    Tatsunori Shimizu, Hidetaka Ota, Ayuto Kodama, Yasuhiro Suzuki, Takako Ohnuma, Rieko Suzuki, Kaoru Sugawara, Yasushi Sato, Hiroyuki Kodama.
      With aging populations in many countries, including Japan, efforts to mitigate the aging-related decline in physical function have gained importance not only for improving individual quality of life but also for mitigating the effects of this loss of function on society. Impaired glucose tolerance, muscle weakness, and cognitive decline are well-known effects of aging. These interrelated factors can create a vicious cycle because impaired glucose tolerance can accelerate muscle weakness and cognitive decline. Unmodulated 40 Hz (u40Hz) stimulation is imperceptible to the human ear and has been reported to improve cognitive function in humans and mice. However, research on the effects of u40Hz stimulation is still limited. This study aimed to report the effects of u40Hz stimulation on glucose tolerance and muscle strength in senescence-accelerated prone (SAMP)-10 mice, a model of accelerated aging. SAMP-10 mice underwent five weeks of u40Hz stimulation followed by glucose-tolerance tests, cognitive and behavioral assessments, and frailty evaluations. In comparison with the control group, the u40Hz-stimulation group showed mitigation of age-related decline in glucose tolerance, a better frailty index (FI), and notably preserved muscle strength. Microarray analysis of stimulated muscle tissue revealed significant upregulation of β-oxidation genes and genes functioning downstream of peroxisome proliferator-activated receptor gamma, and significant downregulation of clock genes. These findings indicate the beneficial effects of u40Hz stimulation on glucose tolerance, muscle strength, and cognitive function, warranting further research in this area.
    Keywords:  aging; glucose tolerance; muscle; unmodulated 40 Hz stimulation
    DOI:  https://doi.org/10.3390/biom14091079
  47. Foods. 2024 Sep 18. pii: 2945. [Epub ahead of print]13(18):
    Antioxidant Peptides and Protein Hydrolysates from Tilapia: Cellular and In Vivo Evidences for Human Health Benefits.
    Wen-Jie Ng, Fai-Chu Wong, Fazilah Abd Manan, Yit-Lai Chow, Ai-Lin Ooi, Mei-Kying Ong, Xuewu Zhang, Tsun-Thai Chai.
      Antioxidant peptides derived from aquatic organisms have attracted tremendous research interest due to their potential applications in human health. Tilapia is one of the most widely farmed aquaculture species globally. The current understanding of tilapia-derived antioxidant peptides is gradually expanding. This review discusses the current knowledge of peptides and protein hydrolysates derived from tilapia muscle, skin, and scales, whose antioxidant capacity has been validated in various cellular and in vivo models. To date, at least 16 peptides and several hydrolysates have been identified from tilapia that protect human and non-human cell models against oxidative injury. Tilapia hydrolysates and peptide mixtures have also shown protective effects in animal models of oxidative stress-associated diseases and exercise-induced oxidative injury and fatigue. The key mechanisms of tilapia hydrolysates and peptide mixtures involve enhancing antioxidant enzyme activities and suppressing radical production. Notably, such hydrolysates also exerted additional in vivo functions, such as anti-inflammatory, anti-diabetic, wound healing, and antiaging properties. Taken together, tilapia-derived antioxidant peptides and hydrolysates represent a valuable source of functional ingredients for applications in functional food, dietary supplements, and therapeutic applications. Continued research into their health benefits is warranted in the future.
    Keywords:  anti-inflammatory; antiaging; antifatigue; aquaculture; bioactive compounds; enzymatic hydrolysis; functional food; oxidative stress; wound healing
    DOI:  https://doi.org/10.3390/foods13182945
  48. bioRxiv. 2024 Sep 19. pii: 2024.09.16.613354. [Epub ahead of print]
    BayesAge 2.0: A Maximum Likelihood Algorithm to Predict Transcriptomic Age.
    Lajoyce Mboning, Emma K Costa, Jingxun Chen, Louis-S Bouchard, Matteo Pellegrini.
      Aging is a complex biological process influenced by various factors, including genetic and environmental influences. In this study, we present BayesAge 2.0, an improved version of our maximum likelihood algorithm designed for predicting transcriptomic age (tAge) from RNA-seq data. Building on the original BayesAge framework, which was developed for epigenetic age prediction, BayesAge 2.0 integrates a Poisson distribution to model count-based gene expression data and employs LOWESS smoothing to capture non-linear gene-age relationships. BayesAge 2.0 provides significant improvements over traditional linear models, such as Elastic Net regression. Specifically, it addresses issues of age bias in predictions, with minimal age-associated bias observed in residuals. Its computational efficiency further distinguishes it from traditional models, as reference construction and cross-validation are completed more quickly compared to Elastic Net regression, which requires extensive hyperparameter tuning. Overall, BayesAge 2.0 represents a notable advance in transcriptomic age prediction, offering a robust, accurate, and efficient tool for aging research and biomarker development.
    DOI:  https://doi.org/10.1101/2024.09.16.613354
  49. EMBO Rep. 2024 Oct 02.
    Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells.
    Shajahan Anver, Ahmed Faisal Sumit, Xi-Ming Sun, Abubakar Hatimy, Konstantinos Thalassinos, Samuel Marguerat, Nazif Alic, Jürg Bähler.
      Genomes produce widespread long non-coding RNAs (lncRNAs) of largely unknown functions. We characterize aal1 (ageing-associated lncRNA), which is induced in quiescent fission yeast cells. Deletion of aal1 shortens the chronological lifespan of non-dividing cells, while ectopic overexpression prolongs their lifespan, indicating that aal1 acts in trans. Overexpression of aal1 represses ribosomal-protein gene expression and inhibits cell growth, and aal1 genetically interacts with coding genes functioning in protein translation. The aal1 lncRNA localizes to the cytoplasm and associates with ribosomes. Notably, aal1 overexpression decreases the cellular ribosome content and inhibits protein translation. The aal1 lncRNA binds to the rpl1901 mRNA, encoding a ribosomal protein. The rpl1901 levels are reduced ~2-fold by aal1, which is sufficient to extend lifespan. Remarkably, the expression of the aal1 lncRNA in Drosophila boosts fly lifespan. We propose that aal1 reduces the ribosome content by decreasing Rpl1901 levels, thus attenuating the translational capacity and promoting longevity. Although aal1 is not conserved, its effect in flies suggests that animals feature related mechanisms that modulate ageing, based on the conserved translational machinery.
    Keywords:   Schizosaccharomyces pombe ; Chronological Lifespan; Protein Translation; RNA Regulation; Ribosomal Protein
    DOI:  https://doi.org/10.1038/s44319-024-00265-9
  50. iScience. 2024 Oct 18. 27(10): 110908
    Quiescence and aging of melanocyte stem cells and a novel association with programmed death-ligand 1.
    NISC Comparative Sequencing Program
      Cellular quiescence is a reversible and tightly regulated stem cell function essential for healthy aging. However, the elements that control quiescence during aging remain poorly defined. Using melanocyte stem cells (McSCs), we find that stem cell quiescence is neither passive nor static. For example, gene expression profiling of the transition from proliferating melanoblasts to quiescent melanocyte stem cells reveals tissue-specific regulation of the immune checkpoint protein PD-L1. In vitro, quiescence assays demonstrate that PD-L1 expression is a physiological attribute of quiescence in this cell lineage and reinforces this cell state. In vivo, a subset of quiescent McSCs is marked by PD-L1. While the overall number of McSCs decreases with age, PD-L1+ McSCs appear resistant to depletion. This phenomenon coincides with an aged McSC pool that exhibits a deeper transcriptomic quiescence. We predict that quiescent PD-L1+ stem cells retained with age may serve as cellular targets for reactivation.
    Keywords:  Functional aspects of cell biology; Stem cells research
    DOI:  https://doi.org/10.1016/j.isci.2024.110908
  51. Nutrients. 2024 Sep 19. pii: 3177. [Epub ahead of print]16(18):
    Filbertone Reduces Senescence in C2C12 Myotubes Treated with Doxorubicin or H2O2 through MuRF1 and Myogenin.
    Sumin Jung, Byungyong Ahn.
      It has been demonstrated that filbertone, the principal flavor compound of hazelnuts, exhibits preventive effects against hypothalamic inflammation, obesity, neurodegenerative diseases, and muscle lipid accumulation. However, its influence on muscle aging has yet to be elucidated. The objective of this study was to investigate the effects of filbertone on muscle aging in C2C12 myotubes subjected to senescence induction by either doxorubicin or hydrogen peroxide. To ascertain the mechanisms by which filbertone exerts its effects, we conducted a series of experiments, including Western blot analysis, reverse transcription quantitative polymerase chain reaction (qRT-PCR), and senescence-associated β-galactosidase (SA-β-gal) staining. Filbertone was markedly observed to decrease not only the protein levels of p53 (p < 0.01) in senescence-induced skeletal muscle cells, but also the gene expression levels of p21 (p < 0.05), a direct target of p53. The expression of muscle-related genes, including myogenin and muscle RING-finger protein-1 (MuRF1), was found to be significantly enhanced in senescent muscle cells following treatment with filbertone (p < 0.05). In addition, the number of senescent skeletal muscle cells exhibiting β-galactosidase activity was found to be markedly reduced in the presence of filbertone (p < 0.01). Collectively, these findings suggest that filbertone plays a pivotal role in the regulation of muscle aging.
    Keywords:  filbertone; muscle aging; p53; senescence
    DOI:  https://doi.org/10.3390/nu16183177
  52. Obes Rev. 2024 Sep 30. e13844
    Development and clinical application of bioelectrical impedance analysis method for body composition assessment.
    Jang Won Son, Byoung-Duck Han, Jonathan P Bennett, Steve Heymsfield, Soo Lim.
      Obesity, which is characterized by excessive body fat, increases the risk of chronic diseases, such as type 2 diabetes, cardiovascular diseases, and certain cancers. Sarcopenia, a decline in muscle mass, is also associated with many chronic disorders and is therefore a major concern in aging populations. Body composition analysis is important in the evaluation of obesity and sarcopenia because it provides information about the distribution of body fat and muscle mass. It is also useful for monitoring nutritional status, disease severity, and the effectiveness of interventions, such as exercise, diet, and drugs, and thus helps assess overall health and longevity. Computed tomography, magnetic resonance imaging, and dual-energy X-ray absorptiometry are commonly used for this purpose. However, they have limitations, such as high cost, long measurement time, and radiation exposure. Instead, bioelectrical impedance analysis (BIA), which was introduced several decades ago and has undergone significant technological advancements, can be used. It is easily accessible, affordable, and importantly, poses no radiation risk, making it suitable for use in hospitals, fitness centers, and even at home. Herein, we review the recent technological developments and clinical applications of BIA to provide an updated understanding of BIA technology and its strengths and limitations.
    Keywords:  body composition; fat; impedance; muscle; obesity; sarcopenia
    DOI:  https://doi.org/10.1111/obr.13844
  53. J Dent Sci. 2024 Oct;19(4): 2332-2340
    Effect of polydatin on the viability and odontogenic differentiation of human dental pulp stem cells: An in-vitro study.
    Rawan Al-Ateeq, Mona Elsafadi, Solaiman Al-Hadlaq.
       Background/purpose: Various materials have been used to promote human dental pulp stem cells (hDPSCs) differentiation to produce dentin bridge formation with less-than-optimal results. Polydatin (PD), a naturally present material with osteogenic properties can be a promising material in the pulp regeneration/repair process. The aim of this study was to evaluate the effect of (PD) on the viability and differentiation of human dental pulp stem cells.
    Materials and methods: PD effect on hDPSCs in terms of cellular viability, alkaline phosphatase (ALP) production, and messenger RNAs (mRNA) of odontogenic markers production using quantitative reverse transcription polymerase chain reaction (RT-qPCR) were evaluated. In addition, mineral deposits were detected with Alizarin red stain.
    Results: The viable hDPSCs in the presence of 0.01 μM and 0.1 μM PD were significantly higher than the control on days 3 and 7, respectively. In addition, ALP activity of hDPSCs was significantly increased with 0.01, 0.1, and 1 μM of PD. In addition, increased expression mRNAs of ALP, osteocalcin (OC), osteonectin (ON), osteopontin (OP), Runt-related transcription factor-2 (RUNX-2), dentin sialophosphoprotein (DSPP), and dentin matrix protein-1 (DMP-1) was observed after PD treatment, however, the difference was not statistically significant. Furthermore, increased size of mineral deposits was observed with PD.
    Conclusion: PD promoted the expression of markers associated with odontogenic differentiation and mineralized tissue deposition in hDPSCs.
    Keywords:  Differentiation; Human dental pulp stem cells; Odontogenic differentiation; Polydatin
    DOI:  https://doi.org/10.1016/j.jds.2024.02.005
  54. Antioxidants (Basel). 2024 Sep 14. pii: 1110. [Epub ahead of print]13(9):
    Senescence Rejuvenation through Reduction in Mitochondrial Reactive Oxygen Species Generation by Polygonum cuspidatum Extract: In Vitro Evidence.
    Jee Hee Yoon, Ye Hyang Kim, Eun Young Jeong, Yun Haeng Lee, Youngjoo Byun, Song Seok Shin, Joon Tae Park.
      Oxidative stress caused by reactive oxygen species (ROS) is one of the major causes of senescence. Strategies to reduce ROS are known to be important factors in reversing senescence, but effective strategies have not been found. In this study, we screened substances commonly used as cosmetic additives to find substances with antioxidant effects. Polygonum cuspidatum (P. cuspidatum) extract significantly reduced ROS levels in senescent cells. A novel mechanism was discovered in which P. cuspidatum extract reduced ROS, a byproduct of inefficient oxidative phosphorylation (OXPHOS), by increasing OXPHOS efficiency. The reduction in ROS by P. cuspidatum extract restored senescence-associated phenotypes and enhanced skin protection. Then, we identified polydatin as the active ingredient of P. cuspidatum extract that exhibited antioxidant effects. Polydatin, which contains stilbenoid polyphenols that act as singlet oxygen scavengers through redox reactions, increased OXPHOS efficiency and subsequently restored senescence-associated phenotypes. In summary, our data confirmed the effects of P. cuspidatum extract on senescence rejuvenation and skin protection through ROS reduction. This novel finding may be used as a treatment in senescence rejuvenation in clinical and cosmetic fields.
    Keywords:  Polygonum cuspidatum; oxidative stress; reactive oxygen species (ROS); senescence rejuvenation; skin aging
    DOI:  https://doi.org/10.3390/antiox13091110
  55. Nat Immunol. 2024 Oct 04.
    DNA-sensing pathways in health, autoinflammatory and autoimmune diseases.
    Mingqi Dong, Katherine A Fitzgerald.
      Detection of microbial DNA is a primary means of host defense. In mammalian cells, DNA-sensing pathways induce robust anti-microbial responses and initiation of adaptive immunity, leading to the eventual clearance of the infectious agent. However, while conferring the advantage of broad detection capability, the sequence-independent recognition mechanisms of most DNA sensors pose a significant challenge for mammalian cells to maintain ignorance to self-DNA under homeostatic conditions. In this Review, we summarize the fundamentals of DNA-sensing pathways and the intricate regulatory networks that keep these pathways in check. In addition, we describe how regulatory restraints can be defective and underlie human autoinflammatory and autoimmune diseases. Further, we discuss therapies in development that limit inflammation fueled by self-DNA or inappropriate activation of DNA-sensing pathways.
    DOI:  https://doi.org/10.1038/s41590-024-01966-y
  56. Biomedicines. 2024 Sep 05. pii: 2030. [Epub ahead of print]12(9):
    Efficacy of an Innovative Poly-Component Formulation in Counteracting Human Dermal Fibroblast Aging by Influencing Oxidative and Inflammatory Pathways.
    Francesca Rosaria Augello, Francesca Lombardi, Alessia Ciafarone, Valeria Ciummo, Serena Altamura, Maurizio Giuliani, Benedetta Cinque, Paola Palumbo.
      Skin aging is characterized by reactive oxygen species (ROS) accumulation, principal players in triggering events associated with aging. Our recent data on the ability of an innovative poly-component formulation (KARISMA Rh Collagen® FACE: K formulation) to suppress the biomolecular events associated with oxidative stress-induced aging prompted us to deepen the mechanisms underlying the observed effects on aged human dermal fibroblasts (HDFs). Here, we evaluated K's ability to perform a direct free radical-scavenging action and modulate anti-oxidant systems by counteracting the inflammatory process in an H2O2-induced cellular senescence model. Standard methods were used to measure scavenging capacity and enzymatic anti-oxidant system activities. Nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) levels were analyzed by Western blot. We assessed pro-inflammatory cytokines, matrix metalloproteinases (MMPs), and advanced glycation end-products (AGEs). Our results show that K counteracted stress-induced aging in a dose-dependent manner by exerting a direct scavenging action and increasing anti-oxidant systems, such as superoxide dismutase (SOD) and catalase (CAT) up to control values. These findings could be associated with increased phospho-Nrf2 (p-Nrf2) expression, generally reduced in aged HDFs following exposure to different concentrations of K formulation. Moreover, K formulation caused a reduction of pro-inflammatory cytokines, interleukin-1β and -6, MMP-1 and -9, and AGE levels, events related to a downregulation of p-NF-κB level. The results indicate that K formulation re-established the normal physiology of HDFs by reducing p-NF-κB expression and restoring Nrf2 activation, thus supporting its efficacious reparative and regenerative action in treating skin aging.
    Keywords:  AGE; NF-κB; Nrf2; anti-oxidant systems; dermal fibroblast; free radical-scavenging; matrix metalloproteinases; poly-component formulation; pro-inflammatory cytokines; skin aging
    DOI:  https://doi.org/10.3390/biomedicines12092030
  57. Front Aging. 2024 ;5 1469479
    Gene co-expression networks reveal sex-biased differences in musculoskeletal ageing.
    Samael Olascoaga, Hugo Tovar, Jesús Espinal-Enríquez.
      Aging is a universal and progressive process involving the deterioration of physiological functions and the accumulation of cellular damage. Gene regulation programs influence how phenotypes respond to environmental and intrinsic changes during aging. Although several factors, including sex, are known to impact this process, the underlying mechanisms remain incompletely understood. Here, we investigate the functional organization patterns of skeletal muscle genes across different sexes and ages using gene co-expression networks (GCNs) to explore their influence on aging. We constructed GCNs for three different age groups for male and female samples, analyzed topological similarities and differences, inferred significant associated processes for each network, and constructed null models to provide statistically robust results. We found that each network is topologically and functionally distinct, with young women having the most associated processes, likely due to reproductive tasks. The functional organization and modularity of genes decline with age, starting from middle age, potentially leading to age-related deterioration. Women maintain better gene functional organization throughout life compared to men, especially in processes like macroautophagy and sarcomere organization. The study suggests that the loss of gene co-expression could be a universal aging marker. This research offers insights into how gene organization changes with age and sex, providing a complementary method to analyze aging.
    Keywords:  functional enrichment analysis; gene co-expression networks for ageing; loss of function in ageing; loss of gene co-expression in ageing; musculoskeletal ageing; sexual dimorphism in ageing
    DOI:  https://doi.org/10.3389/fragi.2024.1469479
  58. Bioorg Chem. 2024 Sep 23. pii: S0045-2068(24)00743-0. [Epub ahead of print]153 107838
    Curcumol derivatives exhibit ameliorating effects on lipopolysaccharide-induced acute lung injury: Synthesis, biological evaluation, structure-activity relationship and action mechanism.
    Gen Li, Yajing Guo, Anna Ma, Dan Wang, Qi Zhang, Chongyan Zhao, Xuling Peng, Liqin Ding, Xi Chen, Feng Qiu.
      Acute lung injury (ALI) is an intricate clinical disease marked by high mortality and a sudden start. Currently, although there are no specific therapeutics for ALI, the administration of anti-inflammatory drugs is a promising treatment strategy. Curcumol, a terpenoid natural product, has demonstrated significant anti-inflammatory activity. Herein, we designed and synthesised 42 curcumol derivatives using curcumol as the core scaffold. These derivatives underwent in vitro screening for anti-inflammatory activity, and their structure-activity relationship was assessed. Among them, derivative 2 exhibited potent anti-inflammatory potential, inhibiting the expression of inflammatory markers at the nanomolar level. In addition, its water solubility was considerably improved, thereby laying the foundation for enhanced druggability. Derivative 2 also ameliorated lipopolysaccharide (LPS)-induced ALI and reduced pulmonary inflammation at a dose of 5 mg/kg. Proteomics analysis revealed that the anti-inflammatory effect of this compound primarily involved the mTOR signalling pathway. Furthermore, molecular docking and cellular thermal shift assays indicated that GSK3β is a critical target of action of derivative 2, as verified via western blotting. These findings suggest that derivative 2 can be a lead therapeutic compound for ALI, with GSK3β emerging as a promising novel target for the development of specific anti-ALI drugs.
    Keywords:  Acute lung injury; Anti-inflammatory; Curcumol; GSK3β; Proteomics; mTOR
    DOI:  https://doi.org/10.1016/j.bioorg.2024.107838
  59. Microorganisms. 2024 Aug 27. pii: 1772. [Epub ahead of print]12(9):
    A Haloarchaeal Transcriptional Regulator That Represses the Expression of CRISPR-Associated Genes.
    Israela Turgeman-Grott, Yarden Shalev, Netta Shemesh, Rachel Levy, Inbar Eini, Metsada Pasmanik-Chor, Uri Gophna.
      Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) systems provide acquired heritable protection to bacteria and archaea against selfish DNA elements, such as viruses. These systems must be tightly regulated because they can capture DNA fragments from foreign selfish elements, and also occasionally from self-chromosomes, resulting in autoimmunity. Most known species from the halophilic archaeal genus Haloferax contain type I-B CRISPR-Cas systems, and the strongest hotspot for self-spacer acquisition by H. mediterranei was a locus that contained a putative transposable element, as well as the gene HFX_2341, which was a very frequent target for self-targeting spacers. To test whether this gene is CRISPR-associated, we investigated it using bioinformatics, deletion, over-expression, and comparative transcriptomics. We show that HFX_2341 is a global transcriptional regulator that can repress diverse genes, since its deletion results in significantly higher expression of multiple genes, especially those involved in nutrient transport. When over-expressed, HFX_2341 strongly repressed the transcript production of all cas genes tested, both those involved in spacer acquisition (cas1, 2 and 4) and those required for destroying selfish genetic elements (cas3 and 5-8). Considering that HFX_2341 is highly conserved in haloarchaea, with homologs that are present in species that do not encode the CRISPR-Cas system, we conclude that it is a global regulator that is also involved in cas gene regulation, either directly or indirectly.
    Keywords:  CRISPR-Cas; Type I-B; archaea; crr; csa; csa3a; haloarchaea; pHM500; regulation; transcription
    DOI:  https://doi.org/10.3390/microorganisms12091772
  60. Arch Gerontol Geriatr. 2024 Sep 26. pii: S0167-4943(24)00320-0. [Epub ahead of print]128 105644
    Berberine extends healthspan and delays neurodegenerative diseases in Caenorhabditis elegans through ROS-dependent PMK-1/SKN-1 activation.
    Yi Xiao, Li Zhang, Hanlin Zhou, Yingwen Cui, Keer Chen, Han Zhang, Qinyi Wu, Fang Liu.
      Oxidative stress, or the chronic generation of reactive oxygen species (ROS), is thought to contribute to the progression of aging and aging related diseases. However, low degree of ROS generation has repeatedly been shown to be associated with beneficial outcomes via activation of protective signaling pathways. Berberine, a natural alkaloid isolated from Rhizomacoptidis, has a long history of medicinal use in both Ayurvedic and traditional Chinese medicine, which possesses anti-cancer, anti-inflammatory and anti-neurodegenerative properties. In this study, we utilize Caenorhabditis elegans to examine the mechanisms by which berberine influences healthspan and neurodegenerative diseases. We find that 10 μM berberine significantly extends healthy lifespan in wild type C. elegans. We further show that berberine generates ROS, which is followed by activation of PMK-1/SKN-1 to extend healthspan. Intriguingly, berberine also delays neurodegenerative diseases such as Alzheimer's and polyglutamine diseases in a PMK-1/SKN-1dependent manner. Our work suggests that berberine may be a viable candidate for the prevention and treatment of aging and aging related diseases.
    Keywords:  Berberine; Healthspan; Neurodegenerative diseases; PMK-1/SKN-1dependent manner; ROS
    DOI:  https://doi.org/10.1016/j.archger.2024.105644
  61. Aging Biol. 2024 Sep 13. 2(1): 20240034
    Pharmacology of Aging: Drosophila as a Tool to Validate Drug Targets for Healthy Lifespan.
    Eliano Dos Santos, Helena M Cochemé.
      Finding effective therapies to manage age-related conditions is an emerging public health challenge. Although disease-targeted treatments are important, a preventive approach focused on aging can be more efficient. Pharmacological targeting of aging-related processes can extend lifespan and improve health in animal models. However, drug development and translation are particularly challenging in geroscience. Preclinical studies have survival as a major endpoint for drug screening, which requires years of research in mammalian models. Shorter-lived invertebrates can be exploited to accelerate this process. In particular, the fruit fly Drosophila melanogaster allows the validation of new drug targets using precise genetic tools and proof-of-concept experiments on drugs impacting conserved aging processes. Screening for clinically approved drugs that act on aging-related targets may further accelerate translation and create new tools for aging research. To date, 31 drugs used in clinical practice have been shown to extend the lifespan of flies. Here, we describe recent advances in the pharmacology of aging, focusing on Drosophila as a tool to repurpose these drugs and study age-related processes.
    DOI:  https://doi.org/10.59368/agingbio.20240034
  62. Cell Rep Med. 2024 Sep 25. pii: S2666-3791(24)00486-5. [Epub ahead of print] 101756
    Gene therapy for chronic pain management.
    Yi-Ze Li, Ru-Rong Ji.
      Despite significant advances in identifying molecular targets for chronic pain over the past two decades, many remain difficult to target with traditional methods. Gene therapies such as antisense oligonucleotides (ASOs), RNA interference (RNAi), CRISPR, and virus-based delivery systems have played crucial roles in discovering and validating new pain targets. While there has been a surge in gene therapy-based clinical trials, those focusing on pain as the primary outcome remain uncommon. This review examines various gene therapy strategies, including ASOs, small interfering RNA (siRNAs), optogenetics, chemogenetics, and CRISPR, and their delivery methods targeting primary sensory neurons and non-neuronal cells, including glia and chondrocytes. We also explore emerging gene therapy tools and highlight gene therapy's clinical potential in pain management, including trials targeting pain-related diseases. Advances in single-cell analysis of sensory neurons and non-neuronal cells, along with the development of new delivery tools, are poised to accelerate the application of gene therapy in pain medicine.
    DOI:  https://doi.org/10.1016/j.xcrm.2024.101756
  63. PLoS One. 2024 ;19(10): e0309961
    CoGTEx: Unscaled system-level coexpression estimation from GTEx data forecast novel functional gene partners.
    Miguel-Angel Cortes-Guzman, Víctor Treviño.
       MOTIVATION: Coexpression estimations are helpful for analysis of pathways, cofactors, regulators, targets, and human health and disease. Ideally, coexpression estimations should consider as many diverse cell types as possible and consider that available data is not uniform across tissues. Importantly, the coexpression estimations accessible today are performed on a "tissue level", which is based on cell type standardized formulations. Little or no attention is paid to overall gene expression levels. The tissue-level estimation assumes that variance expression levels are more important than mean expression levels. Here, we challenge this assumption by estimating a coexpression calculation at the "system level", which is estimated without standardization by tissue, and show that it provides valuable information. We made available a resource to view, download, and analyze both, tissue- and system-level coexpression estimations from GTEx human data.
    METHODS: GTEx v8 expression data was globally normalized, batch-processed, and filtered. Then, PCA, clustering, and tSNE stringent procedures were applied to generate 42 distinct and curated tissue clusters. Coexpression was estimated from these 42 tissue clusters computing the correlation of 33,445 genes by sampling 70 samples per tissue cluster to avoid tissue overrepresentation. This process was repeated 20 times, extracting the minimum value provided as a robust estimation. Three metrics were calculated (Pearson, Spearman, and G-statistic) in two data processing modes, at the system-level (TPM scale) and tissue levels (z-score scale).
    RESULTS: We first validate our tissue-level estimations compared with other databases. Then, by specific analyses in several examples and literature validations of predictions, we show that system-level coexpression estimation differs from tissue-level estimations and that both contain valuable information reflected in biological pathways. We also show that coexpression estimations are associated to transcriptional regulation. Finally, we present CoGTEx, a valuable resource for viewing and analyzing coexpressed genes in human adult tissues from GTEx v8 data. We introduce our web resource to list, view and explore the coexpressed genes from GTEx data.
    CONCLUSION: We conclude that system-level coexpression is a novel and interesting coexpression metric capable of generating plausible predictions and biological hypotheses; and that CoGTEx is a valuable resource to view, compare, and download system- and tissue- level coexpression estimations from GTEx data.
    AVAILABILITY: The web resource is available at http://bioinformatics.mx/cogtex.
    DOI:  https://doi.org/10.1371/journal.pone.0309961
  64. Antioxidants (Basel). 2024 Aug 26. pii: 1035. [Epub ahead of print]13(9):
    Role of Oxidative Stress Signaling, Nrf2, on Survival and Stemness of Human Adipose-Derived Stem Cells Exposed to X-rays, Protons and Carbon Ions.
    Mira Hammad, Rima Salma, Jacques Balosso, Mohi Rezvani, Siamak Haghdoost.
      Some cancers have a poor prognosis and often lead to local recurrence because they are resistant to available treatments, e.g., glioblastoma. Attempts have been made to increase the sensitivity of resistant tumors by targeting pathways involved in the resistance and combining it, for example, with radiotherapy (RT). We have previously reported that treating glioblastoma stem cells with an Nrf2 inhibitor increases their radiosensitivity. Unfortunately, the application of drugs can also affect normal cells. In the present study, we aim to investigate the role of the Nrf2 pathway in the survival and differentiation of normal human adipose-derived stem cells (ADSCs) exposed to radiation. We treated ADSCs with an Nrf2 inhibitor and then exposed them to X-rays, protons or carbon ions. All three radiation qualities are used to treat cancer. The survival and differentiation abilities of the surviving ADSCs were studied. We found that the enhancing effect of Nrf2 inhibition on cell survival levels was radiation-quality-dependent (X-rays > proton > carbon ions). Furthermore, our results indicate that Nrf2 inhibition reduces stem cell differentiation by 35% and 28% for adipogenesis and osteogenesis, respectively, using all applied radiation qualities. Interestingly, the results show that the cells that survive proton and carbon ion irradiations have an increased ability, compared with X-rays, to differentiate into osteogenesis and adipogenesis lineages. Therefore, we can conclude that the use of carbon ions or protons can affect the stemness of irradiated ADSCs at lower levels than X-rays and is thus more beneficial for long-time cancer survivors, such as pediatric patients.
    Keywords:  ADSC; Nrf2 inhibitor; X-rays; adipogenesis; adipose-derived stem cell; carbon ions; differentiation; ionizing radiation; osteogenesis; particle radiation; protons; radiotherapy
    DOI:  https://doi.org/10.3390/antiox13091035
  65. Exp Gerontol. 2024 Oct 01. pii: S0531-5565(24)00247-X. [Epub ahead of print] 112601
    Elucidating the effective age for dietary restriction and the key metabolites involved.
    Jazween Loo, Geetha Gunasekaran, Jen Kit Tan, Jo Aan Goon.
      Dietary restriction (DR) extends lifespan in various species, but its effect at different ages, especially when started later, is unclear. This study used Caenorhabditis elegans to explore the impact of DR at different ages. Worms were divided into control and DR groups, with daily survival monitored. To confirm the occurrence of DR, the expression of DR-sensitive genes namely acdh-1, pyk-1, pck-2 and cts-1 were determined using RT-qPCR. Liquid chromatography mass spectrometry (LC-MS) was employed to observe the changes in metabolites affected by DR. The results indicated that young worms subjected to mild DR displayed the longest lifespan, highlighting the effectiveness of initiating DR at a young age. Increased expression of acdh-1 and pck-2 suggests activation of beta-oxidation and gluconeogenesis, while decreased cts-1 expression indicates a reduced citric acid cycle, further supporting the observed effects of DR in these worms. Metabolomic results indicated that DR decreased the activity of mechanistic Target of Rapamycin (mTOR) and the synthesis of amino acids namely leucine, tyrosine and tryptophan to conserve energy for cell repair and survival. DR also decreased levels of N-acetyl-L-methionine and S-adenosyl-methionine (SAM) in methionine metabolism, thereby promoting autophagy, reducing inflammation, and facilitating the removal of damaged cells and proteins. In conclusion, initiating dietary restriction early in life extends the lifespan by modulating amino acid metabolism and enhancing the autophagy pathway, thereby maintaining cellular wellbeing.
    Keywords:  C. elegans; Dietary restriction; Effective age; LC-MS; Lifespan; PCA
    DOI:  https://doi.org/10.1016/j.exger.2024.112601
  66. Trends Biotechnol. 2024 Oct 03. pii: S0167-7799(24)00253-1. [Epub ahead of print]
    CRISPR/Cas: a powerful tool for designing and improving oil crops.
    Lijie Li, Dangquan Zhang, Zhiyong Zhang, Baohong Zhang.
      Improving oil yield and quality is a major goal for crop breeding, and CRISPR/Cas-mediated genome editing has opened a new era for designing oil crops with enhanced yield and quality. CRISPR/Cas technology can not only increase oil production but also enhance oil quality, including enhancing pharmaceutical and health components, improving oil nutrients, and removing allergic and toxic components. As new molecular targets for oil biosynthesis are discovered and the CRISPR/Cas system is further improved, CRISPR/Cas will become a better molecular tool for designing new oil crops with higher oil production, enhanced nutrients, and improved health components. 'CRISPRized' oil crops will have broad applications both in industry (e.g., as biofuels) and in daily human life.
    Keywords:  CRISPR/Cas; food security; genome editing; health effects; oil; pharmaceuticals
    DOI:  https://doi.org/10.1016/j.tibtech.2024.09.007
  67. Free Radic Biol Med. 2024 Sep 27. pii: S0891-5849(24)00693-2. [Epub ahead of print]
    Human Salivary Histatin 1 Regulating IP3R1/GRP75/VDAC1 Mediated Mitochondrial-Associated Endoplasmic Reticulum Membranes (MAMs) Inhibits Cell Senescence For Diabetic Wound Repair.
    Tinghui Xian, Yi Liu, Yongsheng Ye, Bohua Peng, Jie Huang, Lin Liang, Jiaqing Zhang, Hao Wu, Zhen Lin.
       RATIONALE: Difficulty in skin wound healing is a concern for diabetic patients across the world. Impaired mitochondrial dysfunction and aging-related vascular dysfunction in human umbilical vein endothelial cells (HUVECs) caused by oxidative stress are major impediments to diabetic wound healing. However, research on skin repair at the mechanistic level by improving mitochondrial function and inhibiting oxidative stress-induced HUVEC senescence remains lacking.
    METHODS AND RESULTS: Human saliva effectively inhibits the natural aging of HUVECs through immunodepletion experiments. Histatin 1 (Hst1), a short peptide comprising 38 amino acids, is the primary component of human saliva that prevents HUVEC aging. Based on in vitro findings, Hst1 decreased staining for senescence-associated β-galactosidase activity and expression of mediators of senescence signaling, including p53, p21, and p16. Mechanistically, HUVEC senescence is associated with Hst1-modulated nuclear factor Nrf2 signaling as Hst1 induces ERK-mediated Nrf2 nuclear translocation through NADPH oxidase-dependent ROS regulation, reinforced Nrf2 antioxidant response, and suppressed oxidative stress. RNA sequencing identified that the mitochondrial-related gene set was enriched in the Hst1 group. Coimmunoprecipitation indicated that Hst1 delayed hydrogen peroxide-induced HUVEC senescence by inhibiting mitochondria-associated endoplasmic reticulum (ER) membrane formation mediated by inositol 1,4,5-trisphosphate receptor 1-glucose-regulated protein 75-voltage-dependent anion channel 1 (VDAC1) complex interactions. Furthermore, in aging HUVECs, Hst1 treatment or VDAC1 silencing with small interfering RNA hindered calcium (Ca2+) transfer from the ER to the mitochondria, thereby ameliorating mitochondrial Ca2+ overload and restoring mitochondrial function. In an in vivo mouse model of diabetes mellitus skin defects, Hst1 facilitated wound healing by stimulating the new blood vessel formation and impeding the expression of senescent biomarkers.
    CONCLUSIONS: This study proposes a theoretical solution that Hst1 can restore mitochondrial function by inhibiting oxidative stress or cellular senescence, thereby promoting angiogenesis and diabetic wound repair.
    Keywords:  Cell senescence; Hst1; IP3R1/GRP75/VDAC1 complex; Mitochondria-associated ER membranes; Mitochondrial function; Oxidative stress
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2024.09.046
  68. Nucleic Acids Res. 2024 Oct 01. pii: gkae845. [Epub ahead of print]
    N 2-Alkyl-dG lesions elicit R-loop accumulation in the genome.
    Yinan Wang, Feng Tang, Ting Zhao, Jun Yuan, Andrew H Kellum, Yinsheng Wang.
      Humans are exposed to DNA alkylating agents through endogenous metabolism, environmental exposure and cancer chemotherapy. The resulting alkylated DNA adducts may elicit genome instability by perturbing DNA replication and transcription. R-loops regulate various cellular processes, including transcription, DNA repair, and telomere maintenance. However, unscheduled R-loops are also recognized as potential sources of DNA damage and genome instability. In this study, by employing fluorescence microscopy and R-loop sequencing approaches, we uncovered, for the first time, that minor-groove N2-alkyl-dG lesions elicit elevated R-loop accumulation in chromatin and in plasmid DNA in cells. We also demonstrated that the N2-alkyl-dG-induced R-loops impede transcription elongation and compromise genome integrity. Moreover, genetic depletion of DDX23, a R-loop helicase, renders cells more sensitive toward benzo[a]pyrene diolepoxide, a carcinogen that induces mainly the minor-groove N2-dG adduct. Together, our work unveiled that unrepaired minor-groove N2-alkyl-dG lesions may perturb genome integrity through augmenting R-loop levels in chromatin. Our findings suggest a potential therapeutic strategy involving the combination of R-loop helicase inhibitors with DNA alkylating drugs.
    DOI:  https://doi.org/10.1093/nar/gkae845
  69. Int J Mol Sci. 2024 Sep 14. pii: 9943. [Epub ahead of print]25(18):
    Involvement of Aryl Hydrocarbon Receptor in Longevity and Healthspan: Insights from Humans, Mice, and C. elegans.
    Eva Serna, David Verdú, Alicia Valls, Ángel Belenguer-Varea, Francisco José Tarazona-Santabalbina, Consuelo Borrás, José Viña.
      In previous studies, using transcriptomic analysis, we observed higher levels of aryl hydrocarbon receptor (AHR) gene expression in the peripheral blood cells of centenarians compared to octogenarians. This suggests the potential significance of this receptor in maintaining physiological balance and promoting healthy aging, possibly linked to its critical role in detoxifying xenobiotics. In our current study, we confirmed that AHR expression is indeed higher in centenarians. We employed C. elegans as a model known for its suitability in longevity studies to explore whether the AHR pathway has a significant impact on lifespan and healthspan. Our survival assays revealed that two different mutants of AHR-1 exhibited lower longevity. Additionally, we used a mouse model to examine whether supplementation with pomegranate extract modulates the expression of AHR pathway genes in the liver. Furthermore, we studied a nutritional strategy based on pomegranate extract administration to investigate its potential modulation of life- and healthspan in worms.
    Keywords:  aryl hydrocarbon receptor; lifespan; pomegranate extract; vitality
    DOI:  https://doi.org/10.3390/ijms25189943
  70. Nutr Metab Cardiovasc Dis. 2024 Aug 27. pii: S0939-4753(24)00309-0. [Epub ahead of print]
    Virgin coconut oil mitigates ageing-associated oxidative stress and dyslipidaemia in male Wistar rats.
    Sruthi Panniyan Kandiyil, Anit Jose, Chanjana Mohanan, Soorya Parathodi Illam, Achuthan C Raghavamenon.
       BACKGROUND AND AIM: Ageing often leads to the deterioration of physiological functions, including a decline in antioxidant defences, which can result in various health complications. Exogenous antioxidants have been recognised for their potential to alleviate these age-related health complications. Virgin coconut oil (VCO), known for its antioxidant, anti-inflammatory and anti-lipidemic efficacies, has gained recognition as a functional food with promising benefits. However, the safety of VCO consumption among individuals of the aged and diseased population remains to be fully established.
    METHODS AND RESULTS: Five experimental groups were established, consisting of one control group and four groups administered either "2 mL" or "4 mL" per kg body weight of "HP-VCO" or "F-VCO" daily for six weeks. Body weight, water, and feed intake were monitored. After six weeks, animals were euthanized, blood and organs were collected for analysis. Oxidative stress and dyslipidemia markers were analysed, and liver tissues underwent histological examination. HP-VCO-administered animals exhibited increased serum total cholesterol and triglycerides, whereas F-VCO-fed animals showed reduced triglyceride levels. LDL-cholesterol levels decreased in all VCO-fed groups, accompanied by increased HDL-cholesterol levels. Additionally, all treated groups showed a slight increase in the HMG Co. A/mevalonate ratio. Both VCO-fed animals displayed elevated reduced glutathione levels and reduced glutathione - S transferase activity. Consistent with these findings, decreased conjugated dienes and thiobarbituric acid reactive substances confirmed the improved redox status.
    CONCLUSION: The study indicated that F-VCO is advantageous over VCO prepared by hot pressing as it offers protection against oxidative stress and related degenerative diseases.
    Keywords:  Ageing; Fermented VCO; Hot pressed VCO; Lipid metabolism; Oxidative stress
    DOI:  https://doi.org/10.1016/j.numecd.2024.08.012
  71. Neuroprotection. 2024 Sep;2(3): 182-195
    Microglial senescence in neurodegeneration: Insights, implications, and therapeutic opportunities.
    Tobiloba Samuel Olajide, Toheeb O Oyerinde, Omolabake I Omotosho, Oritoke M Okeowo, Olayemi J Olajide, Omamuyouwi M Ijomone.
      The existing literature on neurodegenerative diseases (NDDs) reveals a common pathological feature: the accumulation of misfolded proteins. However, the heterogeneity in disease onset mechanisms and the specific brain regions affected complicates the understanding of the diverse clinical manifestations of individual NDDs. Dementia, a hallmark symptom across various NDDs, serves as a multifaceted denominator, contributing to the clinical manifestations of these disorders. There is a compelling hypothesis that therapeutic strategies capable of mitigating misfolded protein accumulation and disrupting ongoing pathogenic processes may slow or even halt disease progression. Recent research has linked disease-associated microglia to their transition into a senescent state-characterized by irreversible cell cycle arrest-in aging populations and NDDs. Although senescent microglia are consistently observed in NDDs, few studies have utilized animal models to explore their role in disease pathology. Emerging evidence from experimental rat models suggests that disease-associated microglia exhibit characteristics of senescence, indicating that deeper exploration of microglial senescence could enhance our understanding of NDD pathogenesis and reveal novel therapeutic targets. This review underscores the importance of investigating microglial senescence and its potential contributions to the pathophysiology of NDDs, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Additionally, it highlights the potential of targeting microglial senescence through iron chelation and senolytic therapies as innovative approaches for treating age-related NDDs.
    Keywords:  aging; ferritin; microglia; neurodegenerative diseases; senescence-associated secretory phenotype; senescent
    DOI:  https://doi.org/10.1002/nep3.56
  72. Brain Sci. 2024 Sep 06. pii: 903. [Epub ahead of print]14(9):
    Effect of Chronic Tibolone Administration on Memory and Choline Acetyltransferase and Tryptophan Hydroxylase Content in Aging Mice.
    Tzayaka Castillo-Mendieta, Guadalupe Bautista-Poblet, Angélica Coyoy-Salgado, Emily L Castillo-García, Rodolfo Pinto-Almazán, Claudia Erika Fuentes-Venado, Teresa Neri-Gómez, Christian Guerra-Araiza.
      Gonadal steroids exert different effects on the central nervous system (CNS), such as preserving neuronal function and promoting neuronal survival. Estradiol, progesterone, and testosterone reduce neuronal loss in the CNS in animal models of neurodegeneration. However, hormone replacement therapy has been associated with higher rates of endometrial, prostate, and breast cancer. Tibolone (TIB), the metabolites of which show estrogenic and progestogenic effects, is an alternative to reduce this risk. However, the impact of TIB on memory and learning, as well as on choline acetyltransferase (ChAT) and tryptophan hydroxylase (TPH) levels in the hippocampus of aging males, is unknown. We administered TIB to aged C57BL/6J male mice at different doses (0.01 or 1.0 mg/kg per day for 12 weeks) and evaluated its effects on memory and learning and the content of ChAT and TPH. We assessed memory and learning with object recognition and elevated T-maze tasks. Additionally, we determined ChAT and TPH protein levels in the hippocampus by Western blotting. TIB administration increased the percentage of time spent on the novel object in the object recognition task. In addition, the latency of leaving the enclosed arm increased in both TIB groups, suggesting an improvement in fear-based learning. We also observed decreased ChAT content in the group treated with the 0.01 mg/kg TIB dose. In the case of TPH, no changes were observed with either TIB dose. These results show that long-term TIB administration improves memory without affecting locomotor activity and modulates cholinergic but not serotonergic systems in the hippocampus of aged male mice.
    Keywords:  aging mice; choline acetyltransferase; hippocampus; memory; tibolone; tryptophan hydroxylase
    DOI:  https://doi.org/10.3390/brainsci14090903
  73. Int J Mol Sci. 2024 Sep 13. pii: 9888. [Epub ahead of print]25(18):
    Particulate Matter and Its Molecular Effects on Skin: Implications for Various Skin Diseases.
    Kyungho Paik, Jung-Im Na, Chang-Hun Huh, Jung-Won Shin.
      Particulate matter (PM) is a harmful air pollutant composed of chemicals and metals which affects human health by penetrating both the respiratory system and skin, causing oxidative stress and inflammation. This review investigates the association between PM and skin disease, focusing on the underlying molecular mechanisms and specific disease pathways involved. Studies have shown that PM exposure is positively associated with skin diseases such as atopic dermatitis, psoriasis, acne, and skin aging. PM-induced oxidative stress damages lipids, proteins, and DNA, impairing cellular functions and triggering inflammatory responses through pathways like aryl hydrocarbon receptor (AhR), NF-κB, and MAPK. This leads to increased production of inflammatory cytokines and exacerbates skin conditions. PM exposure exacerbates AD by triggering inflammation and barrier disruption. It disrupts keratinocyte differentiation and increases pro-inflammatory cytokines in psoriasis. In acne, it increases sebum production and inflammatory biomarkers. It accelerates skin aging by degrading ECM proteins and increasing MMP-1 and COX2. In conclusion, PM compromises skin health by penetrating skin barriers, inducing oxidative stress and inflammation through mechanisms like ROS generation and activation of key pathways, leading to cellular damage, apoptosis, and autophagy. This highlights the need for protective measures and targeted treatments to mitigate PM-induced skin damage.
    Keywords:  atopic dermatitis; particulate matter; psoriasis; skin aging; skin disease
    DOI:  https://doi.org/10.3390/ijms25189888
  74. ACS Appl Mater Interfaces. 2024 Sep 30.
    Drug-Loaded Mesoporous Polydopamine Nanoparticles in Chitosan Hydrogels Enable Myocardial Infarction Repair through ROS Scavenging and Inhibition of Apoptosis.
    Tianhu Wang, Yabin Wang, Yingjie Zhang, Zhiyi Fang, Sulei Li, Zhenghui Gu, Yan Ma, Linghuan Wang, Dong Han, Changyong Wang, Jin Zhou, Feng Cao.
      In this study, we synthesized mesoporous polydopamine nanoparticles (MPDA NPs) using an emulsion-induced interface assembly strategy and loaded epigallocatechin gallate (EGCG) into MPDA NPs via electrostatic attraction to form EGCG@MPDA NPs. In the post myocardial infarction (MI) environment, these interventions specifically aimed to eliminate reactive oxygen species (ROS) and facilitate the repair of MI. We further combined them with a thermosensitive chitosan (CS) hydrogel to construct an injectable composite hydrogel (EGCG@MPDA/CS hydrogel). Utilizing in vitro experiments, the EGCG@MPDA/CS hydrogel exhibited excellent ROS-scavenging ability of H9C2 cells under the oxidative stress environment and also could inhibit their apoptosis. The EGCG@MPDA/CS hydrogel significantly promoted left ventricular ejection fraction (LVEF) in infarcted rat models post injection for 28 days compared to the PBS group (51.25 ± 1.73% vs 29.31 ± 0.78%, P < 0.05). In comparison to the PBS group, histological analysis revealed a substantial increase in left ventricular (LV) wall thickness in the EGCG@MPDA/CS hydrogel group (from 0.58 ± 0.03 to 1.39 ± 1.11 mm, P < 0.05). This work presents a novel approach to enhance MI repair by employing the EGCG@MPDA/CS hydrogel. This hydrogel effectively reduces local oxidative stress by ROS and stimulates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.
    Keywords:  EGCG; PDA; chitosan; injectable hydrogel; myocardial infarction
    DOI:  https://doi.org/10.1021/acsami.4c08155
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