bims-caglex 2025-01-12 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2025–01–12
forty papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

Functional Diversity of Senescent Cells in Driving Aging Phenotypes and Facilitating Tissue Regeneration.
Beyond the Hayflick limit: How microbes influence cellular aging.
Dietary Restriction and Lipid Metabolism: Unveiling Pathways to Extended Healthspan.
Suppressing the Aging Phenotype of Mesenchymal Stromal Cells: Are We Ready for Clinical Translation?
Brain aging and rejuvenation at single-cell resolution.
Mitigating Oxidative Stress and Promoting Cellular Longevity with Mushroom Extracts.
Caffeine-Induced Upregulation of pas-1 and pas-3 Enhances Intestinal Integrity by Reducing Vitellogenin in Aged Caenorhabditis elegans Model.
From Bench to Bedside: Translating Cellular Rejuvenation Therapies into Clinical Applications.
[Research progress on anti-aging effects of β-nicotinamide mononucleotide (NMN)].
Resveratrol and Extra Virgin Olive Oil: Protective Agents Against Age-Related Disease.
Nanoformulated phytochemicals in skin anti-aging research: an updated mini review.
The Hippo Signaling Pathway Manipulates Cellular Senescence.
Chronological versus immunological aging: Immune rejuvenation to arrest cognitive decline.
Epigenetic Mechanisms in Aging: Extrinsic Factors and Gut Microbiome.
Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities.
Macrophage Immunometabolism - Emerging Targets for Regrowth in Aging Muscle.
How age affects human hematopoietic stem and progenitor cells and strategies to mitigate HSPC aging.
Senolytic Vaccines from the Central and Peripheral Tolerance Perspective.
Recent advances in biomarkers for senescence: Bridging basic research to clinic.
Enhancing muscle and brain resilience: The role of prehabilitative exercise in mitigating disuse effects.
Dietary cinnamon promotes longevity and extends healthspan via mTORC1 and autophagy signaling.
Multimodal transcriptomics reveal neurogenic aging trajectories and age-related regional inflammation in the dentate gyrus.
Synergistic ROS Reduction Through the Co-Inhibition of BRAF and p38 MAPK Ameliorates Senescence.
Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair.
DeepQA: A Unified Transcriptome-Based Aging Clock Using Deep Neural Networks.
The Protective Role of Vitamin K in Aging and Age-Related Diseases.
Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons.
Mechanisms and early efficacy data of caloric restriction and caloric restriction mimetics in neurodegenerative disease.
White Tea Aqueous Extract: A Potential Anti-Aging Agent Against High-Fat Diet-Induced Senescence in Drosophila melanogaster.
Cellular Senescence in The Cancer Microenvironment.
Effects of Vaccinium-derived antioxidants on human health: the past, present and future.
Analyzing Muscle Stem Cell Function Ex Vivo.
Investigation of the anti-aging effects of active components of Artemia franciscana loaded in hyalurosome.
[Research progress on the mechanism of leucine regulation of protein synthesis in aging skeletal muscle through LAT1].
Intermittent Fasting Enhances Motor Coordination Through Myelin Preservation in Aged Mice.
Synergistic Antioxidant Effects of Molecular Hydrogen and Cold Atmospheric Plasma in Enhancing Mesenchymal Stem Cell Therapy.
Oxygen transport across the lifespan of male Sprague Dawley rats.
Fisetin Alleviates d-Galactose-Induced Senescence in C2C12 Myoblasts: Metabolic and Gene Regulatory Mechanisms.
Genetic Causal Association Between Skin Microbiota and Biological Aging: Evidence From a Mendelian Randomization Analysis.
Long-term intake of Tamogi-take mushroom (Pleurotus cornucopiae) mitigates age-related cardiovascular dysfunction and extends healthy life expectancy.

J Biochem. 2025 Jan 06. pii: mvae098. [Epub ahead of print]

Functional Diversity of Senescent Cells in Driving Aging Phenotypes and Facilitating Tissue Regeneration.

Yasuhiro Nakano, Yoshikazu Johmura.

  As the global population continues to age, understanding the complex role of cellular senescence and its implications in healthy lifespans has gained increasing prominence. Cellular senescence is defined as the irreversible cessation of cell proliferation, accompanied by the secretion of a range of pro-inflammatory factors, collectively termed the senescence-associated secretory phenotype (SASP), in response to various cellular stresses. While the accumulation of senescent cells has been strongly implicated in the aging process and the pathogenesis of age-related diseases owing to their pro-inflammatory properties, recent research has also highlighted their essential roles in processes such as tumour suppression, tissue development, and repair. This review provides a comprehensive examination of the dual nature of senescent cells, evaluating their deleterious contributions to chronic inflammation, tissue dysfunction, and disease, as well as their beneficial roles in maintaining physiological homeostasis. Additionally, we explored the therapeutic potential of senolytic agents designed to selectively eliminate detrimental senescent cells while considering the delicate balance between transient and beneficial senescence and the persistence of pathological senescence. A deeper understanding of these dynamics is critical to develop novel interventions aimed at mitigating age-related dysfunctions and enhancing healthy life expectancies.

Keywords:  Age-related diseases; Cellular senescence; Healthspan; Senolytics; Tissue regeneration

DOI:  https://doi.org/10.1093/jb/mvae098
Ageing Res Rev. 2025 Jan 07. pii: S1568-1637(25)00003-0. [Epub ahead of print]104 102657

Beyond the Hayflick limit: How microbes influence cellular aging.

Mohammad Abavisani, Saba Faraji, Negar Ebadpour, Sercan Karav, Amirhossein Sahebkar.

  Cellular senescence, a complex biological process resulting in permanent cell-cycle arrest, is central to aging and age-related diseases. A key concept in understanding cellular senescence is the Hayflick Limit, which refers to the limited capacity of normal human cells to divide, after which they become senescent. Senescent cells (SC) accumulate with age, releasing pro-inflammatory and tissue-remodeling factors collectively known as the senescence-associated secretory phenotype (SASP). The causes of senescence are multifaceted, including telomere attrition, oxidative stress, and genotoxic damage, and they extend to influences from microbial sources. Research increasingly emphasizes the role of the microbiome, especially gut microbiota (GM), in modulating host senescence processes. Beneficial microbial metabolites, such as short-chain fatty acids (SCFAs), support host health by maintaining antioxidant defenses and reducing inflammation, potentially mitigating senescence onset. Conversely, pathogenic bacteria like Pseudomonas aeruginosa and Helicobacter pylori introduce factors that damage host DNA or increase ROS, accelerating senescence via pathways such as NF-κB and p53-p21. This review explores the impact of bacterial factors on cellular senescence, highlighting the role of specific bacterial toxins in promoting senescence. Additionally, it discusses how dysbiosis and the loss of beneficial microbial species further contribute to age-related cellular deterioration. Modulating the gut microbiome to delay cellular senescence opens a path toward targeted anti-aging strategies. This work underscores the need for deeper investigation into microbial influence on aging, supporting innovative interventions to manage and potentially reverse cellular senescence.

Keywords:  Aging; Cellular senescence; Microbiota; Oxidative stress

DOI:  https://doi.org/10.1016/j.arr.2025.102657
Nutrients. 2024 Dec 23. pii: 4424. [Epub ahead of print]16(24):

Dietary Restriction and Lipid Metabolism: Unveiling Pathways to Extended Healthspan.

Hye-Yeon Lee, Kyung-Jin Min.

  Dietary restriction (DR) has been reported to be a significant intervention that influences lipid metabolism and potentially modulates the aging process in a wide range of organisms. Lipid metabolism plays a pivotal role in the regulation of aging and longevity. In this review, we summarize studies on the significant role of lipid metabolism in aging in relation to DR. As a potent intervention to slow down aging, DR has demonstrated promising effects on lipid metabolism, influencing the aging processes across various species. The current review focuses on the relationships among DR-related molecular signaling proteins such as the sirtuins, signaling pathways such as the target of rapamycin and the insulin/insulin-like growth factor (IGF)-1, lipid metabolism, and aging. Furthermore, the review presents research results on diet-associated changes in cell membrane lipids and alterations in lipid metabolism caused by commensal bacteria, highlighting the importance of lipid metabolism in aging. Overall, the review explores the interplay between diet, lipid metabolism, and aging, while presenting untapped areas for further understanding of the aging process.

Keywords:  Ins/IGF-1; cell membrane; commensal bacteria; dietary restriction; healthspan; lipid profile; sirtuin; target of rapamycin

DOI:  https://doi.org/10.3390/nu16244424
Biomedicines. 2024 Dec 11. pii: 2811. [Epub ahead of print]12(12):

Suppressing the Aging Phenotype of Mesenchymal Stromal Cells: Are We Ready for Clinical Translation?

Ilaria Roato, Matteo Visca, Federico Mussano.

  Mesenchymal stem/stromal cells (MSCs) are involved in the maintenance and regeneration of a large variety of tissues due to their stemness and multi-lineage differentiation capability. Harnessing these advantageous features, a flurry of clinical trials have focused on MSCs to treat different pathologies, but only few protocols have received regulatory approval so far. Among the various causes hindering MSCs' efficacy is the emergence of cellular senescence, which has been correlated with specific characteristics, such as morphological and epigenetic alterations, DNA damage, ROS production, mitochondrial dysfunction, telomere shortening, non-coding RNAs, loss of proteostasis, and a peculiar senescence-associated secretory phenotype. Several strategies have been investigated for delaying or even hopefully reverting the onset of senescence, as assessed by the senescent phenotype of MSCs. Here, the authors reviewed the most updated literature on the potential causes of senescence, with a particular emphasis on the current and future therapeutic approaches aimed at reverting senescence and/or extending the functional lifespan of stem cells.

Keywords:  MSCs; rejuvenation; senescence

DOI:  https://doi.org/10.3390/biomedicines12122811
Neuron. 2025 Jan 08. pii: S0896-6273(24)00885-7. [Epub ahead of print]113(1): 82-108

Brain aging and rejuvenation at single-cell resolution.

Eric D Sun, Rahul Nagvekar, Angela N Pogson, Anne Brunet.

  Brain aging leads to a decline in cognitive function and a concomitant increase in the susceptibility to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. A key question is how changes within individual cells of the brain give rise to age-related dysfunction. Developments in single-cell "omics" technologies, such as single-cell transcriptomics, have facilitated high-dimensional profiling of individual cells. These technologies have led to new and comprehensive characterizations of brain aging at single-cell resolution. Here, we review insights gleaned from single-cell omics studies of brain aging, starting with a cell-type-centric overview of age-associated changes and followed by a discussion of cell-cell interactions during aging. We highlight how single-cell omics studies provide an unbiased view of different rejuvenation interventions and comment on the promise of combinatorial rejuvenation approaches for the brain. Finally, we propose new directions, including models of brain aging and neural stem cells as a focal point for rejuvenation.

Keywords:  aging; brain; cell-cell interactions; multi-omics; regeneration; rejuvenation; single-cell transcriptomics; spatial transcriptomics

DOI:  https://doi.org/10.1016/j.neuron.2024.12.007
Foods. 2024 Dec 13. pii: 4028. [Epub ahead of print]13(24):

Mitigating Oxidative Stress and Promoting Cellular Longevity with Mushroom Extracts.

Menna-Allah E Abdelkader, Hatungimana Mediatrice, Dongmei Lin, Zhanxi Lin, Sarah A Aggag.

  Oxidative stress can disrupt the body's ability to fight harmful free radicals, leading to premature aging and various health complications. This study investigated the antioxidant and anti-aging properties of four medicinal and edible mushrooms: Ganoderma lucidum, Hericium erinaceus, Pleurotus ostreatus, and Agaricus bisporus. The antioxidant activity of mushroom extracts was evaluated using (DPPH-ABTS-Reducing power). The anti-aging effects were assessed using Human Skin Fibroblasts (HSF) cells subjected to D-galactose-induced aging (30 g/L/72 h) and treated with mushroom extracts (0.03-0.25 mg/mL/72 h). The results demonstrated that all mushrooms have significant antioxidant and anti-aging properties, with low concentrations of extracts (0.03 mg/mL) effectively promoting cell proliferation at an 87% rate in the Agaricus bisporus extract, enhancing cell cycle progression by reducing the arrested cells in the G0/G1 phase to 75%, and promoting DNA synthesis in S phase by more than 16.36% in the Hericium erinaceus extract. Additionally, the extracts reduced DNA damage and Reactive Oxygen Species (ROS) levels, protecting cells from oxidative stress and potentially contributing to anti-aging effects. The mushrooms also exhibited immunomodulatory and anti-inflammatory effects by upregulating the IL-2, IL-4, and downregulating IL-6 expression, indicating their potential to promote general health. These findings suggest the potential of mushroom extracts as natural agents for reducing the negative effects of aging while promoting cellular health. Further research is required to explore the specific bioactive compounds responsible for these beneficial effects and to evaluate their efficacy in vivo.

Keywords:  D-gal; DNA damage; IL-genes; ROS; anti-aging; antioxidants; cell cycle; mushroom; telomere length

DOI:  https://doi.org/10.3390/foods13244028
Nutrients. 2024 Dec 12. pii: 4298. [Epub ahead of print]16(24):

Caffeine-Induced Upregulation of pas-1 and pas-3 Enhances Intestinal Integrity by Reducing Vitellogenin in Aged Caenorhabditis elegans Model.

Mijin Lee, Jea Lee, Dongyeon Kim, Hyemin Min, Yhong-Hee Shim.

  Background: Intestinal aging is characterized by declining protein homeostasis via reduced proteasome activity, which are hallmarks of age-related diseases. Our previous study showed that caffeine intake improved intestinal integrity with age by reducing vitellogenin (VIT, yolk protein) in C. elegans. In this study, we investigated the regulatory mechanisms by which caffeine intake improves intestinal integrity and reduces vitellogenin (VIT) production in aged Caenorhabditis elegans. Methods: We performed RNA-seq analysis, and qRT-PCR to validate and confirm the RNA-seq results. Transgenic worms with VIT-2::GFP and VIT-6::GFP were used for measuring VIT production. dsRNAi was conducted to elucidate the roles of pas-1 and pas-3 genes. Results:pas-1 and pas-3, a C. elegans ortholog of human PASM4, was upregulated by caffeine intake. They reduced VIT production by repressing unc-62, a transcriptional activator of vit expression. Interestingly, vit-2 was required for pas-1 and pas-3 expression, and RNAi of pas-1 and pas-3 promoted intestinal atrophy and colonization, suggesting a balancing mechanism for VIT levels in intestinal health. Additionally, lifespan was extended by caffeine intake (2 ± 0.05 days), however, this effect was not observed by pas-1 but not pas-3 RNAi, suggesting that the mode of action for an anti-aging effect of caffeine through pas-1 and pas-3 is distinctive. The lifespan extended by pas-1 was mediated by SKN-1 activation. Conclusions: Caffeine intake enhances intestinal health through proteasome activity and extends lifespan in aged C. elegans by upregulating pas-1 and pas-3. These findings suggest that caffeine consumption mitigates age-related proteasome impairment and maintains intestinal integrity during aging.

Keywords:  Caenorhabditis elegans; caffeine; intestinal health; pas-1; pas-3; yolk protein

DOI:  https://doi.org/10.3390/nu16244298
Cells. 2024 Dec 12. pii: 2052. [Epub ahead of print]13(24):

From Bench to Bedside: Translating Cellular Rejuvenation Therapies into Clinical Applications.

Timur Saliev, Prim B Singh.

  Cellular rejuvenation therapies represent a transformative frontier in addressing age-related decline and extending human health span. By targeting fundamental hallmarks of aging-such as genomic instability, epigenetic alterations, mitochondrial dysfunction, and cellular senescence-these therapies aim to restore youthful functionality to cells and tissues, offering new hope for treating degenerative diseases. Recent advancements have showcased a range of strategies, including epigenetic reprogramming, senolytic interventions, mitochondrial restoration, stem cell-based approaches, and gene-editing technologies like CRISPR. Each modality has demonstrated substantial potential in preclinical models and is now being cautiously explored in early-stage clinical trials. However, translating these therapies from the laboratory to clinical practice presents unique challenges: safety concerns, delivery precision, complex regulatory requirements, ethical considerations, and high costs impede widespread adoption. This review examines the current landscape of cellular rejuvenation, highlighting key advancements, potential risks, and the strategies needed to overcome these hurdles.

Keywords:  CRISPR; induced pluripotent stem cells; mesenchymal stem cells; rejuvenation; senolytics

DOI:  https://doi.org/10.3390/cells13242052
Sheng Li Xue Bao. 2024 Dec 25. 76(6): 1032-1042

[Research progress on anti-aging effects of β-nicotinamide mononucleotide (NMN)].

Miao Han, Jin-Lian Hua.

β-Nicotinamide mononucleotide (NMN), as the precursor of nicotinamide adenine dinucleotide (NAD), plays an important role in enhancing NAD levels. Intake of NMN can alter the composition and vitality of gut microbiota, restore mitochondrial function, inhibit inflammatory pathways, improve metabolism, counteract oxidative stress, and alleviate inflammation. NMN significantly improves recovery from aging-related diseases, such as diminished heart function, reduced fertility, memory decline, and diabetes. NMN demonstrates both efficacy and safety in anti-aging. The use of NMN in China has gradually gained acceptance, highlighting the importance of exploring the mechanism of NMN in anti-aging effects and improving the biosynthesis of NMN. In addition, NMN in combination with stem cells hold promise in the treatment of aging-related degenerative diseases and promote overall human and animal health.
Nutrients. 2024 Dec 10. pii: 4258. [Epub ahead of print]16(24):

Resveratrol and Extra Virgin Olive Oil: Protective Agents Against Age-Related Disease.

Evgeny Morkovin, Roman Litvinov, Alexey Koushner, Denis Babkov.

  Resveratrol and extra virgin olive oil are both recognized for their potential protective effects against age-related diseases. This overview highlights their mechanisms of action, health benefits, and the scientific evidence supporting their roles in promoting longevity and cognitive health. A literature search was conducted. Important findings related to the health benefits, mechanisms of action, and clinical implications of resveratrol and EVOO were summarized. Both resveratrol and EVOO have complementary mechanisms that may enhance their anti-aging effects. Resveratrol and EVOO are promising age-related disease-protective agents. Their antioxidant, anti-inflammatory, and neuroprotective properties contribute to improved health outcomes and longevity. Incorporating these compounds into a balanced diet may offer significant benefits for aging populations, supporting cognitive health and reducing the risk of chronic diseases. Continued research is essential to fully understand their mechanisms and optimize their use in clinical settings. Future research should focus on investigating the synergistic effects of resveratrol and EVOO when consumed together, as they may enhance each other's bioavailability and efficacy in promoting health; conducting extensive clinical trials to confirm the long-term benefits of these compounds in various populations, particularly in aging individuals; further exploring the molecular pathways through which resveratrol and EVOO exert their effects, including their interactions with gut microbiota and metabolic pathways.

Keywords:  Mediterranean diet; age-related diseases; extra virgin olive oil; resveratrol

DOI:  https://doi.org/10.3390/nu16244258
3 Biotech. 2025 Jan;15(1): 31

Nanoformulated phytochemicals in skin anti-aging research: an updated mini review.

Andrea G Uriostegui-Pena, Andrea Torres-Copado, Adriana Ochoa-Sanchez, Gabriel Luna-Bárcenas, Padmavati Sahare, Sujay Paul.

  Skin aging is characterized by progressive loss of functionality and regenerative potential of the skin, resulting in the appearance of wrinkles, irregular pigmentation, a decrease of elasticity, dryness, and rough texture. Damage to the skin caused by oxidative stress could substantially be slowed down by the use of phytochemicals that function as natural antioxidants. Although phytochemicals have immense potential as anti-aging medicines, their effectiveness as therapeutic agents is restricted by their poor solubility, biodistribution, stability, and hydrophilicity. Given their improved stability, solubility, efficacy, and occlusive properties, nanoformulations have emerged as promising drug delivery platforms for phytochemicals to achieve anti-aging effects. The efficacy of these nanoformulated phytochemicals in suppressing enzymes that accelerate skin aging, such as collagenase, tyrosinase and hyaluronidase, as well as enhancing superoxide dismutase, catalase, and collagen levels to improve skin appearance during aging has been demonstrated.

Keywords:  Anti-aging property; Antioxidant; Nanoformulations; Phytochemicals; Skin; Therapeutics

DOI:  https://doi.org/10.1007/s13205-024-04197-y
Cells. 2024 Dec 26. pii: 13. [Epub ahead of print]14(1):

The Hippo Signaling Pathway Manipulates Cellular Senescence.

Chiharu Miyajima, Mai Nagasaka, Hiromasa Aoki, Kohki Toriuchi, Shogo Yamanaka, Sakura Hashiguchi, Daisuke Morishita, Mineyoshi Aoyama, Hidetoshi Hayashi, Yasumichi Inoue.

  The Hippo pathway, a kinase cascade, coordinates with many intracellular signals and mediates the regulation of the activities of various downstream transcription factors and their coactivators to maintain homeostasis. Therefore, the aberrant activation of the Hippo pathway and its associated molecules imposes significant stress on tissues and cells, leading to cancer, immune disorders, and a number of diseases. Cellular senescence, the mechanism by which cells counteract stress, prevents cells from unnecessary damage and leads to sustained cell cycle arrest. It acts as a powerful defense mechanism against normal organ development and aging-related diseases. On the other hand, the accumulation of senescent cells without their proper removal contributes to the development or worsening of cancer and age-related diseases. A correlation was recently reported between the Hippo pathway and cellular senescence, which preserves tissue homeostasis. This review is the first to describe the close relationship between aging and the Hippo pathway, and provides insights into the mechanisms of aging and the development of age-related diseases. In addition, it describes advanced findings that may lead to the development of tissue regeneration therapies and drugs targeting rejuvenation.

Keywords:  Hippo pathway; cancer; cellular senescence

DOI:  https://doi.org/10.3390/cells14010013
Neuron. 2025 Jan 08. pii: S0896-6273(24)00882-1. [Epub ahead of print]113(1): 140-153

Chronological versus immunological aging: Immune rejuvenation to arrest cognitive decline.

Leyre Basurco, Miguel Angel Abellanas, Maitreyee Purnapatre, Paola Antonello, Michal Schwartz.

  The contemporary understanding that the immune response significantly supports higher brain functions has emphasized the notion that the brain's condition is linked in a complex manner to the state of the immune system. It is therefore not surprising that immunity is a key factor in shaping brain aging. In this perspective article, we propose amending the Latin phrase "mens sana in corpore sano" ("a healthy mind in a healthy body") to "a healthy mind in a healthy immune system." Briefly, we discuss the emerging understanding of the pivotal role of the immune system in supporting lifelong brain maintenance, how the aging of the immune system impacts the brain, and how the potential rejuvenation of the immune system could, in turn, help revitalize brain function, with the ultimate ambitious goal of developing an anti-aging immune therapy.

Keywords:  aging; brain; immune aging; microglia; neuroimmunology; rejuvenation; senescence

DOI:  https://doi.org/10.1016/j.neuron.2024.12.004
Genes (Basel). 2024 Dec 14. pii: 1599. [Epub ahead of print]15(12):

Epigenetic Mechanisms in Aging: Extrinsic Factors and Gut Microbiome.

Alejandro Borrego-Ruiz, Juan J Borrego.

   BACKGROUND/OBJECTIVES: Aging is a natural physiological process involving biological and genetic pathways. Growing evidence suggests that alterations in the epigenome during aging result in transcriptional changes, which play a significant role in the onset of age-related diseases, including cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. For this reason, the epigenetic alterations in aging and age-related diseases have been reviewed, and the major extrinsic factors influencing these epigenetic alterations have been identified. In addition, the role of the gut microbiome and its metabolites as epigenetic modifiers has been addressed.
RESULTS: Long-term exposure to extrinsic factors such as air pollution, diet, drug use, environmental chemicals, microbial infections, physical activity, radiation, and stress provoke epigenetic changes in the host through several endocrine and immune pathways, potentially accelerating the aging process. Diverse studies have reported that the gut microbiome plays a critical role in regulating brain cell functions through DNA methylation and histone modifications. The interaction between genes and the gut microbiome serves as a source of adaptive variation, contributing to phenotypic plasticity. However, the molecular mechanisms and signaling pathways driving this process are still not fully understood.
CONCLUSIONS: Extrinsic factors are potential inducers of epigenetic alterations, which may have important implications for longevity. The gut microbiome serves as an epigenetic effector influencing host gene expression through histone and DNA modifications, while bidirectional interactions with the host and the underexplored roles of microbial metabolites and non-bacterial microorganisms such as fungi and viruses highlight the need for further research.

Keywords:  aging; epigenetics; extrinsic factors; gut microbiome; microbial metabolites; neurodegenerative diseases

DOI:  https://doi.org/10.3390/genes15121599
Neurotherapeutics. 2025 Jan 06. pii: S1878-7479(24)00206-X. [Epub ahead of print] e00519

Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities.

Hannah R Hudson, Xuehan Sun, Miranda E Orr.

  Cellular senescence is a cell state triggered by programmed physiological processes or cellular stress responses. Stress-induced senescent cells often acquire pathogenic traits, including a toxic secretome and resistance to apoptosis. When pathogenic senescent cells form faster than they are cleared by the immune system, they accumulate in tissues throughout the body and contribute to age-related diseases, including neurodegeneration. This review highlights evidence of pathogenic senescent cells in the brain and their role in Alzheimer's disease (AD), the leading cause of dementia in older adults. We also discuss the progress and challenges of senotherapies, pharmacological strategies to clear senescent cells or mitigate their toxic effects, which hold promise as interventions for AD and related dementias (ADRD).

Keywords:  Alzheimer's disease; Biology of aging; Neurescence; Neurodegeneration; tau

DOI:  https://doi.org/10.1016/j.neurot.2024.e00519
Am J Physiol Endocrinol Metab. 2025 Jan 06.

Macrophage Immunometabolism - Emerging Targets for Regrowth in Aging Muscle.

Zachary J Fennel, Ryan M O'Connell, Micah J Drummond.

  The recovery from muscle atrophy is impaired with aging as characterized by improper muscle remodeling and sustained functional deficits. Age-related deficits in muscle regrowth are tightly linked with the loss of early pro-inflammatory macrophage responses and subsequent cellular dysregulation within the skeletal muscle niche. Macrophage inflammatory phenotype is regulated at the metabolic level, highlighting immunometabolism as an emerging strategy to enhance macrophage responses and restore functional muscle regrowth. Accordingly, metabolic targets with an emphasis on glycolytic, hypoxia, and redox-related pathways stand out for their role in promoting macrophage inflammation and enhancing muscle regrowth in aging. Here we highlight promising immuno-metabolic targets which could be leveraged to restore optimal pro-inflammatory macrophage function in aging and enhance muscle regrowth following muscular atrophy.

Keywords:  aging; immune cells; inflammation; metabolism; muscle remodeling

DOI:  https://doi.org/10.1152/ajpendo.00403.2024
Exp Hematol. 2025 Jan 07. pii: S0301-472X(25)00002-5. [Epub ahead of print] 104711

How age affects human hematopoietic stem and progenitor cells and strategies to mitigate HSPC aging.

Xueling Li, Jianwei Wang, Linping Hu, Tao Cheng.

Hematopoietic stem cells (HSCs) are central to blood formation and play a pivotal role in hematopoietic and systemic aging. With aging, HSCs undergo significant functional changes, such as an increased stem cell pool, declined homing and reconstitution capacity, and skewed differentiation towards myeloid and megakaryocyte/platelet progenitors. These phenotypic alterations are likely due to the expansion of certain clones, known as clonal hematopoiesis (CH), which leads to disrupted hematopoietic homeostasis, including anemia, impaired immunity, higher risks of hematological malignancies, and even associations with cardiovascular disease, highlighting the broader impact of HSC aging on overall health. HSC aging is driven by a range of mechanisms involving both intrinsic and extrinsic factors, such as DNA damage accumulation, epigenetic remodeling, inflammaging and metabolic regulation. In this review, we summarize the update understanding of age-related changes in HSPCs and the mechanisms underlie the aging process in mammalian models, especially in human study. Additionally, we provide insights into potential therapeutic strategies to counteract aging process and enhance HSC regenerative capacity, which will support therapeutic interventions and promote healthy aging.

DOI: https://doi.org/10.1016/j.exphem.2025.104711
Vaccines (Basel). 2024 Dec 10. pii: 1389. [Epub ahead of print]12(12):

Senolytic Vaccines from the Central and Peripheral Tolerance Perspective.

Mariia I Vasilieva, Rimma O Shatalova, Kseniia S Matveeva, Vadim V Shindyapin, Ekaterina Minskaia, Roman A Ivanov, Daniil V Shevyrev.

  Preventive medicine has proven its long-term effectiveness and economic feasibility. Over the last century, vaccination has saved more lives than any other medical technology. At present, preventative measures against most infectious diseases are successfully used worldwide; in addition, vaccination platforms against oncological and even autoimmune diseases are being actively developed. At the same time, the development of medicine led to an increase in both life expectancy and the proportion of age-associated diseases, which pose a heavy socio-economic burden. In this context, the development of vaccine-based approaches for the prevention or treatment of age-related diseases opens up broad prospects for extending the period of active longevity and has high economic potential. It is well known that the development of age-related diseases is associated with the accumulation of senescent cells in various organs and tissues. It has been demonstrated that the elimination of such cells leads to the restoration of functions, rejuvenation, and extension of the lives of experimental animals. However, the development of vaccines against senescent cells is complicated by their antigenic heterogeneity and the lack of a unique marker. In addition, senescent cells are the body's own cells, which may be the reason for their low immunogenicity. This mini-review discusses the mechanisms of central and peripheral tolerance that may influence the formation of an anti-senescent immune response and be responsible for the accumulation of senescent cells with age.

Keywords:  ageing; central tolerance; peripheral tolerance; senescence; senescent-associated antigens; senescent-specific antigens; senolytic vaccines

DOI:  https://doi.org/10.3390/vaccines12121389
Geriatr Gerontol Int. 2025 Jan 03.

Recent advances in biomarkers for senescence: Bridging basic research to clinic.

Takeshi Fukumoto, Tatsuo Shimosawa, Mitsutaka Yakabe, Shota Yoshida, Yohko Yoshida.

  In this review, we review the current status of biomarkers for aging and possible perspectives on anti-aging or rejuvenation from the standpoint of biomarkers. Aging is observed in all cells and organs, and we focused on research into senescence in the skin, musculoskeletal system, immune system, and cardiovascular system. Commonly used biomarkers include SA-βgal, cell-cycle markers, senescence-associated secretory phenotype (SASP) factors, damage-associated molecular patterns (DAMPs), and DNA-damage-related markers. In addition, each organ or cell has its specific markers. Generally speaking, a combination of biomarkers is required to define age-related changes. When considering the translation of basic research, biomarkers that are highly sensitive, highly specific, with validation and reliability as well as being non-invasive are optimal; however, currently reported markers do not fulfill the prerequisite for biomarkers. In addition, rodent models of aging do not necessarily represent human aging, and markers in rodent or cell models are not applicable in clinical settings. The prerequisite of clinically applicable biomarkers is that they provide useful information for clinical decision-making, such as predicting disease risk, diagnosing disease, monitoring disease progression, or guiding treatment decisions. Therefore, the development of non-invasive robust, reliable, and useful biomarkers in humans is necessary to develop anti-aging therapy for humans. Geriatr Gerontol Int 2025; ••: ••-••.

Keywords:  T cell; epigenetic marker; genetic marker; sarcopenia; ultraviolet

DOI:  https://doi.org/10.1111/ggi.15054
J Physiol. 2025 Jan 06.

Enhancing muscle and brain resilience: The role of prehabilitative exercise in mitigating disuse effects.

Casper Soendenbroe, Carl-Johan Boraxbekk, Abigail L Mackey.

  Short-term disuse leads to rapid declines in muscle mass and strength. These declines are driven by changes at all levels of the neuromuscular system; the brain, spinal cord and skeletal muscle. In addition to neural input from the central and peripheral nervous systems to the muscle, molecular factors originating in the muscle can be transported to the central nervous system. These interactions highlight the interconnected nature of the neuromuscular system during exercise and disuse, and form the basis for this review. Although it is well known that physical activity confers a myriad of health benefits, a recent interest in targeted exercise before periods of disuse or immobility, termed prehabilitation, has emerged. Clinical studies within multiple medical specialities suggest positive effects of prehabilitative exercise on preserving muscle function, reducing adverse outcomes and shortening the length of hospital stay. Yet, the studies available are few and heterogeneous, and the underlying protective mechanisms of prehabilitative exercise remain elusive. In this review, we examine the ramifications of disuse across all levels of the neuromuscular system and explore how prehabilitation may counteract these effects. We summarize these mechanisms into three primary categories: (1) enhancing pre-disuse capacity; (2) establishing neural and muscle memory; and (3) fostering structural adaptations in both muscle and brain.

Keywords:  muscle memory; muscle–brain cross‐talk; neuromuscular system; physical activity; prehabilitation

DOI:  https://doi.org/10.1113/JP284499
Aging Cell. 2025 Jan 06. e14448

Dietary cinnamon promotes longevity and extends healthspan via mTORC1 and autophagy signaling.

Yuling Guo, Qing Zhang, Bi Zhang, Tong Pan, Elizabeth A Ronan, Anthony Huffman, Yongqun He, Ken Inoki, Jianfeng Liu, X Z Shawn Xu.

  Cinnamon, renowned for its aromatic flavor, represents one of the most widely used spices worldwide. Cinnamon is also considered beneficial to human health with therapeutic potential for treating various diseases, ranging from diabetes and cancer to neurodegenerative diseases. However, the mechanisms underlying cinnamon's health benefits remain elusive. It is also unclear whether cinnamon has any role in aging. Using C. elegans as a model, here we show that feeding worms cinnamaldehyde (CA), the active ingredient in cinnamon oil, prolongs longevity. CA also promotes stress resistance and reduces β-Amyloid toxicity in a C. elegans model of Alzheimer's disease. Mechanistically, CA exerts its beneficial effects through mTORC1 and autophagy signaling. Interestingly, CA promotes longevity by inducing a dietary restriction-like state without affecting food intake, suggesting CA as a dietary restriction mimetic. In human cells, CA exerts a similar effect on mTORC1 and autophagy signaling, suggesting a conserved mechanism. Our results demonstrate that dietary cinnamon promotes both lifespan and healthspan and does so by regulating mTORC1 and autophagy signaling.

Keywords:   C. elegans ; aging; lifespan; longevity

DOI:  https://doi.org/10.1111/acel.14448
Nat Neurosci. 2025 Jan 06.

Multimodal transcriptomics reveal neurogenic aging trajectories and age-related regional inflammation in the dentate gyrus.

Yicheng Wu, Vladyslav I Korobeynyk, Margherita Zamboni, Felix Waern, John Darby Cole, Sarah Mundt, Melanie Greter, Jonas Frisén, Enric Llorens-Bobadilla, Sebastian Jessberger.

The mammalian dentate gyrus (DG) is involved in certain forms of learning and memory, and DG dysfunction has been implicated in age-related diseases. Although neurogenic potential is maintained throughout life in the DG as neural stem cells (NSCs) continue to generate new neurons, neurogenesis decreases with advancing age, with implications for age-related cognitive decline and disease. In this study, we used single-cell RNA sequencing to characterize transcriptomic signatures of neurogenic cells and their surrounding DG niche, identifying molecular changes associated with neurogenic aging from the activation of quiescent NSCs to the maturation of fate-committed progeny. By integrating spatial transcriptomics data, we identified the regional invasion of inflammatory cells into the hippocampus with age and show here that early-onset neuroinflammation decreases neurogenic activity. Our data reveal the lifelong molecular dynamics of NSCs and their surrounding neurogenic DG niche with age and provide a powerful resource to understand age-related molecular alterations in the aging hippocampus.

DOI: https://doi.org/10.1038/s41593-024-01848-4
Antioxidants (Basel). 2024 Nov 28. pii: 1465. [Epub ahead of print]13(12):

Synergistic ROS Reduction Through the Co-Inhibition of BRAF and p38 MAPK Ameliorates Senescence.

Myeong Uk Kuk, Duyeol Kim, Yun Haeng Lee, Jee Hee Yoon, Ji Ho Park, Yoo Jin Lee, Byeong Hyeon So, Minseon Kim, Hyung Wook Kwon, Youngjoo Byun, Joon Tae Park.

  Reactive oxygen species (ROS)-mediated damage to macromolecules and cellular organelles is one of the major causes of senescence. Therapeutic strategies that lower ROS levels have been proposed as important treatments for senescence, but effective mechanisms for reducing ROS levels have not been discovered. Here, we aimed to find a combination that has a synergistic effect on ROS reduction using senomorphics known to reduce ROS. Combination treatment with BRAF inhibitor SB590885 and p38 MAPK inhibitor SB203580 showed a synergistic effect on ROS reduction compared to treatment with either drug alone. The synergistic effect of ROS reduction through this combination led to a synergistic effect that restored mitochondrial function and ameliorated senescence-associated phenotypes. To elucidate the underlying mechanism by which the synergistic effect of the two drugs reverses senescence, we performed RNA sequencing and identified metallothionein 2A (MT2A) as a key gene. MT2A was upregulated in response to combination therapy, and overexpression of MT2A led to a decrease in ROS and subsequent recovery of senescence-associated phenotypes, similar to the effects of combination therapy. Taken together, we found a drug combination that showed synergistic effects on ROS reduction, which contributed to the recovery of senescence-associated phenotypes through MT2A gene regulation. This study opens up a new avenue in aging research by demonstrating that combination therapy with existing senomorphics can enhance the ability to reverse senescence and that similar reversal effects can be achieved through gene regulation regulated by combination therapy.

Keywords:  BRAF inhibitor; metallothionein 2A (MT2A); p38 MAPK inhibitor; reactive oxygen species (ROS)

DOI:  https://doi.org/10.3390/antiox13121465
Biomedicines. 2024 Dec 11. pii: 2808. [Epub ahead of print]12(12):

Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair.

Svetlana N Khodyreva, Nadezhda S Dyrkheeva, Olga I Lavrik.

  The nervous system is susceptible to DNA damage and DNA repair defects, and if DNA damage is not repaired, neuronal cells can die, causing neurodegenerative diseases in humans. The overall picture of what is known about DNA repair mechanisms in the nervous system is still unclear. The current challenge is to use the accumulated knowledge of basic science on DNA repair to improve the treatment of neurodegenerative disorders. In this review, we summarize the current understanding of the function of DNA damage repair, in particular, the base excision repair and double-strand break repair pathways as being the most important in nervous system cells. We summarize recent data on the proteins involved in DNA repair associated with neurodegenerative diseases, with particular emphasis on PARP1 and ND-associated proteins, which are involved in DNA repair and have the ability to undergo liquid-liquid phase separation.

Keywords:  C9orf72; FUS; NONO; SFPQ; TDP-43; alpha synuclein; amyloid beta; base excision repair; direct DNA repair; homologous recombination; huntingtin; liquid–liquid phase separation; mismatch repair; neurodegenerative disease; nonhomologous end joining; poly(ADP-ribose) polymerase 1; tau protein

DOI:  https://doi.org/10.3390/biomedicines12122808
Aging Cell. 2025 Jan 05. e14471

DeepQA: A Unified Transcriptome-Based Aging Clock Using Deep Neural Networks.

Hongqian Qi, Hongchen Zhao, Enyi Li, Xinyi Lu, Ningbo Yu, Jinchao Liu, Jianda Han.

Understanding the complex biological process of aging is of great value, especially as it can help develop therapeutics to prolong healthy life. Predicting biological age from gene expression data has shown to be an effective means to quantify aging of a subject, and to identify molecular and cellular biomarkers of aging. A typical approach for estimating biological age, adopted by almost all existing aging clocks, is to train machine learning models only on healthy subjects, but to infer on both healthy and unhealthy subjects. However, the inherent bias in this approach results in inaccurate biological age as shown in this study. Moreover, almost all existing transcriptome-based aging clocks were built around an inefficient procedure of gene selection followed by conventional machine learning models such as elastic nets, linear discriminant analysis etc. To address these limitations, we proposed DeepQA, a unified aging clock based on mixture of experts. Unlike existing methods, DeepQA is equipped with a specially designed Hinge-Mean-Absolute-Error (Hinge-MAE) loss so that it can train on both healthy and unhealthy subjects of multiple cohorts to reduce the bias of inferring biological age of unhealthy subjects. Our experiments showed that DeepQA significantly outperformed existing methods for biological age estimation on both healthy and unhealthy subjects. In addition, our method avoids the inefficient exhaustive search of genes, and provides a novel means to identify genes activated in aging prediction, alternative to such as differential gene expression analysis.

DOI: https://doi.org/10.1111/acel.14471
Nutrients. 2024 Dec 16. pii: 4341. [Epub ahead of print]16(24):

The Protective Role of Vitamin K in Aging and Age-Related Diseases.

Julia Kaźmierczak-Barańska, Bolesław T Karwowski.

  Aging is an inevitable aspect of life, but age-related diseases are not an inseparable part of the aging process, and their risk can be reduced through a healthy lifestyle. Vitamin K has a broader impact than just blood clotting, and yet it remains overshadowed by other vitamins and underestimated by both doctors and consumers. Vitamin K (VK) is a multifunctional micronutrient with anti-inflammatory and antioxidant properties, whose deficiency may cause age-related diseases such as cardiovascular diseases, neurodegenerative diseases and osteoporosis. There is a growing body of evidence supporting the role of vitamin K as a protective nutrient in aging and inflammation. This review summarizes the current knowledge regarding the molecular aspects of the protective role of vitamin K in aging and age-related diseases and its clinical implications.

Keywords:  aging; inflammation; oxidative stress; vitamin K

DOI:  https://doi.org/10.3390/nu16244341
Antioxidants (Basel). 2024 Dec 04. pii: 1482. [Epub ahead of print]13(12):

Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons.

Leonora Szabo, Imane Lejri, Amandine Grimm, Anne Eckert.

  The accumulation of damaged mitochondria has long been considered a hallmark of the aging process. Among various factors, age-related mitochondrial alterations comprise bioenergetic impairments and disturbances in reactive oxygen species (ROS) control, thereby negatively affecting mitochondrial performance and ultimately accelerating aging. Previous studies have revealed that polyamine spermidine appears to exert health-protective and lifespan-promoting effects. Notably, recent findings have also described a spermidine-induced improvement in age-associated mitochondrial dysfunction, but the beneficial effects of spermidine on aged mitochondria have not been entirely examined yet. Here, we show that spermidine positively regulates several parameters related to mitochondrial bioenergetics and mitochondrial redox homeostasis in young and aged human-induced pluripotent stem cell-derived neurons. We report that spermidine treatment increases adenosine triphosphate production and mitochondrial membrane potential, which is accompanied by an attenuation in mitochondrial ROS levels in both age groups. Furthermore, we demonstrate a spermidine-mediated amelioration in mitochondrial respiration in both young and aged neurons. Overall, our findings suggest that nutritional spermidine supplementation might represent an attractive therapeutic approach to enhance mitochondrial function, consequently decelerating aging.

Keywords:  aging; bioenergetics; induced pluripotent stem cell-derived neurons; mitochondria; oxidative stress; spermidine

DOI:  https://doi.org/10.3390/antiox13121482
Neuroscience. 2025 Jan 04. pii: S0306-4522(25)00006-5. [Epub ahead of print]

Mechanisms and early efficacy data of caloric restriction and caloric restriction mimetics in neurodegenerative disease.

Anchal Trisal, Abhishek Kumar Singh.

  Neurodegenerative disorders (NDDs) have been prevalent for more than a decade, and the number of individuals affected per year has increased exponentially. Among these NDDs, Alzheimer's disease, which causes extreme cognitive impairment, and Parkinson's disease, characterized by impairments in motor activity, are the most prevalent. While few treatments are available for clinical practice, they have minimal effects on reversing the neurodegeneration associated with these debilitating diseases. Lifestyle modifications and dietary choices are emerging and promising approaches to combat these disorders. Of the lifestyle changes that one could adopt, a major habit is caloric restriction. Caloric restriction (CR) is a lifestyle modification in which the amount of calories ingested is reduced to a significant amount without resulting in malnutrition. However, maintaining such a lifestyle is challenging. As alternatives, certain compounds have been recognized to mimic the effects produced by CR. These compounds are called caloric restriction mimetics (CRMs). Among these compounds, some have been designated established CRMs, namely, resveratrol, metformin, and rapamycin, whereas several other candidates are termed potential CRMs because of a lack of conclusive evidence of their effects. The potential CRMs discussed in this review are quercetin, chrysin, astragalin, apigenin, curcumin, epigallocatechin-3-gallate, and NAD+ precursors. This review aims to provide an overview of these CRMs' effectiveness in preventing neurodegenerative disorders associated with aging. Moreover, we highlight the clinical relevance of these compounds by discussing in detail the results of clinical trials on them.

Keywords:  Alzheimer’s disease; Caloric restriction mimetics; Clinical trials; Parkinson’s disease; Preclinical studies

DOI:  https://doi.org/10.1016/j.neuroscience.2025.01.004
Foods. 2024 Dec 13. pii: 4034. [Epub ahead of print]13(24):

White Tea Aqueous Extract: A Potential Anti-Aging Agent Against High-Fat Diet-Induced Senescence in Drosophila melanogaster.

Yan Huang, Miaoyuan He, Jianming Zhang, Shilong Cheng, Xi Cheng, Haoran Chen, Guangheng Wu, Fang Wang, Shaoxiao Zeng.

  White tea has been scientifically proven to exhibit positive biological effects in combating chronic diseases, including cancer, metabolic syndrome, etc. Nevertheless, the anti-aging activity and mechanism of white tea on organisms exposed to a high-fat diet remain unexplored. Herein, we prepared a white tea aqueous extract (WTAE) from white peony in Fuding and assessed its in vivo antioxidant and anti-aging effects by employing a Drosophila melanogaster senescence model induced by lard, delving into the underlying molecular mechanisms through which the WTAE contributes to lifespan improvement. Notably, the WTAE significantly extended the lifespan of Drosophila fed a high-fat diet and partially restored the climbing ability of Drosophila on a high-fat diet, accompanied by increased activities of copper-zinc superoxide dismutase, manganese-superoxide dismutase, and catalase and decreased lipid hydroperoxide levels in Drosophila. Furthermore, transcriptomic analysis indicated that the WTAE countered aging triggered by a high-fat diet via activating oxidative phosphorylation, neuroactive ligand-receptor interactions, and more pathways, as well as inhibiting circadian rhythm-fly, protein processing in the endoplasmic reticulum, and more pathways. Our findings suggest that WTAE exhibits excellent inhibitory activity against high-fat diet-induced senescence and holds promising potential as an anti-aging agent that can be further developed.

Keywords:  Drosophila melanogaster; RNA-seq; anti-aging; high-fat diet; white tea aqueous extract

DOI:  https://doi.org/10.3390/foods13244034
J Biochem. 2025 Jan 06. pii: mvaf001. [Epub ahead of print]

Cellular Senescence in The Cancer Microenvironment.

Satoru Meguro, Makoto Nakanishi.

  In this aging society, the number of patients suffering from age-related diseases, including cancer, is increasing. Cellular senescence is a cell fate that involves permanent cell cycle arrest. Accumulated senescent cells in tissues over time present senescence-associated secretory phenotype (SASP) and make the inflammatory context, disturbing the tumor microenvironment. In particular, the effect of senescent cancer-associated fibroblasts on cancer progression has recently come under the spotlight. Although scientific evidence on the impact of cellular senescence on cancer is emerging, the association between cellular senescence and cancer is heterogeneous and the comprehensive mechanism is still not revealed. Recently, a therapy targeting senescent cells, senotherapeutics, has been reported to be effective against cancer in preclinical research and even clinical trials. With further research, the development of senotherapeutics as a novel cancer therapy is expected.

Keywords:  cancer; cancer-associated fibroblast; cellular senescence; senescent cell; senotherapeutics

DOI:  https://doi.org/10.1093/jb/mvaf001
Front Mol Biosci. 2024 ;11 1520661

Effects of Vaccinium-derived antioxidants on human health: the past, present and future.

Amrita Ghosh, Samir C Debnath, Abir U Igamberdiev.

  Dietary intake of Vaccinium berries has demonstrated significant potential in preventing many risk factors associated with metabolic syndromes in the human population. In recent years, a multitude of research has shown the role of antioxidants derived from Vaccinium berries on chronic diseases such as cardiovascular disorders, diabetes, obesity, and cancer. Several studies have also investigated the effect of Vaccinium berry consumption on their ability to modulate the risk factors associated with oxidative stress, vascular function, inflammation, and lipid metabolism. Regarding cancer, studies showed that the consumption of berries reduces inflammation, inhibits angiogenesis, protects against DNA damage within the cell, and controls apoptosis and proliferation rates in malignant tumours. However, which components are responsible for the health benefits is still unclear. Reports show that whole berry consumption usually confers positive effects on human health, and the health-promoting potentials are likely due to the presence of polyphenols with antioxidant activities. Among these polyphenols, various Vaccinium berry species have been reported to contain anthocyanins and flavonoids. These two polyphenolic compounds are known to have higher antioxidant activity and are beneficial for human health. There are now several studies and human clinical trials documenting the beneficial effects of Vaccinium berries, and these findings suggest that they may be promising for preventing and treating neurodegenerative diseases. This review focuses primarily on dietary Vaccinium berries consumption effects on human health and their potential role as therapeutic agents.

Keywords:  Vaccinium; anthocyanin; antioxidants; berries; flavonoids; phenolics

DOI:  https://doi.org/10.3389/fmolb.2024.1520661
Methods Mol Biol. 2025 Jan 09.

Analyzing Muscle Stem Cell Function Ex Vivo.

Julia von Maltzahn.

  Muscle stem cells (MuSCs) lose a large proportion of their characteristics when removed from their niche, hampering the analysis of muscle stem cell functionality. However, the isolation and culture of single floating myofibers with their adjacent muscle stem cells allow the short-term culture and manipulation of muscle stem cells in conditions as close as possible to the endogenous niche. Here, the isolation, culture and transfection with siRNA of muscle stem cells on their adjacent myofibers from young as well as old mice are described.

Keywords:  Aging; Differentiation; Muscle stem cell; Myofiber; Satellite cell; Stem cell

DOI:  https://doi.org/10.1007/7651_2024_589
Sci Rep. 2025 Jan 08. 15(1): 1293

Investigation of the anti-aging effects of active components of Artemia franciscana loaded in hyalurosome.

Mona Sadat Mirtaleb, Mahvash Khodabandeh Shahraky, Abdolkhaleg Deezagi, Danial Shafiee.

  With the advancement of biotechnology in the marine industry, an increasing utilization of marine ingredients in skincare products has been observed in recent years. Encapsulating Artemia franciscana extract and its derivatives in a novel phospholipid vesicle called hyalurosome presents innovative strategies for drug delivery systems and anti-aging products. In this study, we developed nano hyalurosomes containing Artemia franciscana active components. Partially purification of proteins in the Artemia franciscana extract was performed using ion exchange chromatography, specifically targeting Hsp40 and Artemin. The physicochemical properties of the hyalurosomes were characterized, revealing nanoparticle sizes ranging from 100 to 130 nm, zeta potential between - 57 and - 41.2 mV. The biological compatibility of the fabricated hyalurosomes was tested in vitro on mice fibroblast cells. Results indicated that formulations containing hyalurosomes exhibited no cytotoxicity. In-vivo studies employing H&E and Mason's trichrome staining demonstrated an increase in the dermal layer of the skin on male mice and collagen production following treatment with different formulations containing hyalurosomes. Therefore, these formulations are considered promising candidates for anti-aging effects. Stability study at 4 °C for 60 days validated by FE-SEM imaging. In conclusion, hyalurosomes fabricated with Artemia franciscana extract and its diverse active molecules successfully achieved enhanced loading and penetration into the deeper layers of the skin, and it can be a suitable candidate for the treatment of skin aging and rejuvenation.

Keywords:  Artemia franciscana; Hyalurosome; Marine biotechnology; Nano drug delivery; Skin regeneration

DOI:  https://doi.org/10.1038/s41598-024-83731-7
Sheng Li Xue Bao. 2024 Dec 25. 76(6): 1001-1018

[Research progress on the mechanism of leucine regulation of protein synthesis in aging skeletal muscle through LAT1].

Yu Ke, Zhi-Qiang Dai, Ying Yang, Hui-Wen Wu, Yan Zhao, Hua-Yu Shang, Zhi Xia.

Age-related sarcopenia is a degenerative disease characterized by the decline in skeletal muscle mass and function during the aging process. Anabolic resistance, which refers to the diminished response of skeletal muscle to anabolic stimulation from leucine and other nutrients, is a significant contributing factor to its development. Recent studies have suggested that large neutral amino acid-transporter 1 (LAT1/SLC7A5) may play an important role in enhancing leucine's effects on protein synthesis in aging skeletal muscle. In this paper, the structure and function of LAT1 and its key molecules regulating aging skeletal muscle protein synthesis were reviewed, and the potential relationship between LAT1, as a transmembrane transporter of leucine, and protein synthesis in aging skeletal muscle was analyzed. The aim is to explore new mechanisms and insights for prevention and treatment of age-related sarcopenia, and provide reference for the application of relevant targets in clinical translational medicine.
Aging Cell. 2025 Jan 08. e14476

Intermittent Fasting Enhances Motor Coordination Through Myelin Preservation in Aged Mice.

Zhuang Liu, Ziyue Zhao, Hongying Du, Qingqing Zhou, Mei Li, Zhu Gui, Jinfeng Wu, Yunling Gao, Ning Zheng, Yu Zhang, Ailian Du, Hongxing Wang, Jie Wang.

  Integrating dietary interventions have been extensively studied for their health benefits, such as Alzheimer's disease, Huntington's disease, and aging. However, it is necessary to fully understand the mechanisms of long-term effects and practical applications of these dietary interventions for health. A 10-week intermittent fasting (IMF) regimen was implemented on the aging animals in the current study. The variations of cerebral functions were analyzed employing a comprehensive experimental design that includes behavioral tests, neuroimaging, and ultrastructural analysis, such as resting-state functional MRI (rsfMRI), EEG/EMG recordings, transmission electron microscopy, and immunohistochemistry. Over a 10-week regimen, IMF significantly improved locomotor activity, motor coordination, and muscle strength compared to controls (p < 0.01). Resting-state fMRI (rsfMRI) demonstrated that IMF modulates brain-wide functional connectivity, enhancing communication between key brain regions. Advanced imaging techniques revealed increased expression of myelin-related proteins, including myelin basic protein (MBP), and myelin-associated glycoprotein (MAG), indicating enhanced myelin integrity and repair, particularly in axons with diameters < 400 nm (p < 0.01). These findings suggest that IMF may mitigate age-related declines by promoting better neuronal signaling. This study highlights the potential function of IMF as a non-pharmacological intervention to promote brain health and mitigate cognitive decline in aging populations.

Keywords:  aging animals; intermittent fasting; myelin basic protein; myelin‐associated glycoprotein; resting state functional MRI

DOI:  https://doi.org/10.1111/acel.14476
Antioxidants (Basel). 2024 Dec 23. pii: 1584. [Epub ahead of print]13(12):

Synergistic Antioxidant Effects of Molecular Hydrogen and Cold Atmospheric Plasma in Enhancing Mesenchymal Stem Cell Therapy.

Mikhail Yu Artamonov, Felix A Pyatakovich, Inessa A Minenko.

  In regenerative medicine, mesenchymal stem cells (MSCs) have shown their importance and potential in tissue reconstruction and immune system modification. However, such cells' potential is often diminished by factors such as oxidative stress, immune rejection, and inadequate engraftment. This review highlights the role of molecular hydrogen (H2) and cold atmospheric plasma (CAP) as adjunct therapies to improve the effectiveness of MSC therapy. H2 has strong antioxidative and anti-inflammatory actions as it quenches reactive oxygen species and positively stimulates the Nrf2 pathway that promotes MSC survival and life. CAP, being a modulated source of ROS and RNS, also assists MSCs by altering the cellular redox balance, thus facilitating cellular adaptation, migration, and differentiation. H2 and CAP in conjunction with each other assist in establishing an ambience favorable for promoting MSCs' survival and growth abilities, and reduce the healing time in various pathways such as wound, neuroprotection, and ischemia. Besides these concerns, this review also covers the best administration routes and doses of H2 and CAP together with MSCs in therapy. This study informs on a novel dual method aimed at improving the outcome of MSC therapy while adding several molecular targets and relevant clinical uses concerning these therapies. Research of the future has to deal with bettering these protocols so that the therapeutic benefits can be maximized without long-term implications for clinical applications.

Keywords:  cold atmospheric plasma; mesenchymal stem cells; molecular hydrogen; oxidative stress; regenerative medicine

DOI:  https://doi.org/10.3390/antiox13121584
Biogerontology. 2025 Jan 08. 26(1): 38

Oxygen transport across the lifespan of male Sprague Dawley rats.

William H Nugent, Aleksander S Golub, Roland N Pittman, Bjorn K Song.

  Human populations are experiencing unprecedented growth and longevity with lingering knowledge gaps of the characteristics, mechanisms, and pathologies of senescence. Invasive measurements and long-term control conditions for longitudinal studies are infeasible, necessitating the need for surrogate animal models. Rats have short lifespans (2-3 years) with translatable cardiovascular systems, and Sprague Dawley microcirculatory preparations are key to studying the oxygen transport mechanisms critical to the loss of skeletal muscle function in aging. Here we present baseline physiological data of 61 male, Sprague Dawley rats at 3, 6, 12, 18, and 24 months of age. Anesthetized animals were surgically prepared for femoral arterial and venous cannulations, tracheal intubation, and exteriorization of the spinotrapezius muscle. Measurements included cardiovascular function, blood gases, and peripheral tissue interstitial oxygen tension (PISFO2) using phosphorescence quenching microscopy. Intrinsic heart rates decreased with age without significant changes to blood pressure. Arterial oxygen tension declined 17% by 18 and 24 Months (p < 0.05) while pACO2 and PISFO2 were unchanged. Lactate was elevated at 12 and 18 Months along with an alkaline shift in blood pH. Heart rate and decreased pAO2 decoupled from pACO2 are conserved phenomena in human aging. The continuity of resting PISFO2 despite an anaerobic shift in metabolism may be due to declining mitochondrial function and dysregulation of the vascular response to hypoxemia, which are also present in aged humans. These physiological and microcirculatory data offer a useful experimental model for investigating the detailed changes in oxygen supply and demand that affect senescing skeletal muscles in rats and humans.

Keywords:  Aging; Microcirculation; Oxygen; Phosphorescence quenching method; Spinotrapezius muscle; Sprag Dawley rat

DOI:  https://doi.org/10.1007/s10522-024-10180-0
J Proteome Res. 2025 Jan 08.

Fisetin Alleviates d-Galactose-Induced Senescence in C2C12 Myoblasts: Metabolic and Gene Regulatory Mechanisms.

Yue Zhang, Wenfang Wu, Caihua Huang, Donghai Lin.

  Skeletal muscle aging poses a major threat to the health and quality of life of elderly individuals. Fisetin, a natural polyphenolic compound, exhibits various biological activities; however, its role in preventing skeletal muscle cell aging is still unclear. This study aimed to elucidate the effects of fisetin on skeletal muscle aging using a d-galactose-induced C2C12 myoblast senescence model. Fisetin treatment effectively ameliorated d-galactose-induced aging damage and restored cellular functionality by improving cell viability, reducing the accumulation of the senescence marker enzyme SA-β-gal, and decreasing the expression of key aging marker proteins, p16 and p53. NMR-based metabolomics and RNA-seq transcriptomics analyses revealed that fisetin regulates several critical metabolic pathways, including glutathione metabolism, glycine, serine and threonine metabolism, as well as taurine and hypotaurine metabolism. This regulation led to the restoration of amino acid metabolism, stabilization of cellular energy homeostasis, and the preservation of membrane integrity. In addition, fisetin inhibited calcium signaling and JAK-STAT pathways, reduced cellular stress responses and reversed senescence-induced cell cycle arrest. Together, these findings highlight the potential of fisetin as a therapeutic agent to combat skeletal muscle aging and restore cellular homeostasis, offering a promising avenue for the development of antiaging treatments for skeletal muscle degeneration.

Keywords:  NMR-based metabolomics; cellular senescence; fisetin; myoblast; transcriptomics

DOI:  https://doi.org/10.1021/acs.jproteome.4c00939
J Cosmet Dermatol. 2025 Jan;24(1): e16762

Genetic Causal Association Between Skin Microbiota and Biological Aging: Evidence From a Mendelian Randomization Analysis.

Yuan Li, Liwen Ma, Lipan Fan, Chuyan Wu, Dan Luo, Feng Jiang.

   BACKGROUND: The skin microbiota, a complex community of microorganisms residing on the skin, plays a crucial role in maintaining skin health and overall homeostasis. Recent research has suggested that alterations in the composition and function of the skin microbiota may influence the aging process. However, the causal relationships between specific skin microbiota and biological aging remain unclear. Mendelian randomization (MR) analysis provides a powerful tool to explore these causal links by utilizing genetic variants as instrumental variables, thereby minimizing confounding factors and reverse causality that often complicate observational studies.
METHODS: We utilized a two-sample MR approach with population-based cross-sectional data from two German cohorts, KORA FF4 (n = 324) and PopGen (n = 273). In total, GWAS summary data from 1656 skin samples and datasets on accelerated biological age were analyzed to investigate the causal relationship between skin microbiota and accelerated biological aging. The primary analysis was performed using the inverse variance weighted (IVW) method with random effects and was further supported by MR-Egger regression, Cochran's Q test, and a range of sensitivity analyses.
RESULTS: The MR analysis revealed that for biological age acceleration (BioageAccel), the IVW analysis identified protective effects from certain skin microbiota, including Alphaproteobacteria_Dry (p = 0.046), Asv033_sebaceous (p = 0.043), Burkholderiales_Moist (p = 0.008), and Proteobacteria_Moist (p = 0.042). Similar protective effects were observed for Burkholderiales_Moist (p = 0.045) and Proteobacteria_Moist (p = 0.012) in the weighted median analysis. In contrast, Paracoccus_Moist (p = 0.013) and Proteobacteria_Sebaceous (p = 0.005) were associated with accelerated aging. When using PhenoAge acceleration as the outcome, the IVW analysis linked skin microbiota like Asv005_Dry (p = 0.026), ASV039_Dry (p = 0.003), Betaproteobacteria_Sebaceous (p = 0.038), and Chryseobacterium_Moist (p = 0.013) with accelerated aging. The weighted median analysis supported these findings and also identified protective effects from ASV011_Dry (p = 0.021), ASV023_Dry (p = 0.040), Bacteroidales_Dry (p = 0.022), Enhydrobacter_Moist (p = 0.038), Proteobacteria_Moist (p = 0.002), and Rothia_Moist (p = 0.038).
CONCLUSIONS: This two-sample MR study reveals potential causal relationships between skin microbiota and aging. However, to confirm these findings, further randomized controlled trials (RCTs) are necessary.

Keywords:  GWAS; Mendelian randomization; biological aging; causal relationship; skin microbiota

DOI:  https://doi.org/10.1111/jocd.16762
NPJ Aging. 2025 Jan 08. 11(1): 1

Long-term intake of Tamogi-take mushroom (Pleurotus cornucopiae) mitigates age-related cardiovascular dysfunction and extends healthy life expectancy.

Michio Sato, Daisuke Torigoe, Yuya Kinoshita, Momoka Cyuman, Chitoku Toda, Masaru Sato, Kazutaka Ikeda, Tsuyoshi Kadomatsu, Haruki Horiguchi, Jun Morinaga, Hirotaka Fukami, Taichi Sugizaki, Keishi Miyata, Ryoko Kusaba, Yusuke Okadome, Eiji Matsunaga, Koichi Node, Yuichi Oike.

Age-related declines in cardiac function and exercise tolerance interfere with healthy living and decrease healthy life expectancy in older individuals. Tamogi-take mushrooms (Pleurotus cornucopiae) are known to contain high levels of Ergothioneine (EGT), an antioxidant with potential health benefits. In this study, we assessed the possibility that long-term consumption of Tamogi-take mushrooms might attenuate age-related decline in cardiac and vascular endothelial function in mice. We found that long-term intake of Tamogi-take mushrooms significantly maintained cardiac and vascular endothelial function and improved exercise tolerance in mice. Long-term mushroom consumption also increased levels of Nrf2 (Nuclear factor E2-related factor 2) protein in heart tissues and increased translation of HO-1 (Heme Oxygenase 1) proteins, which have antioxidant effects in heart and aortic tissues. Finally, long-term Tamogi-take mushroom consumption inhibited ROS accumulation with aging and reduced expression of inflammatory biomarkers. We conclude that ingestion of Tamogi-take mushrooms could serve as a dietary intervention to promote cardiovascular health, support healthy aging and slow the progression of age-related diseases.

DOI: https://doi.org/10.1038/s41514-024-00191-z