bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2025–03–16
fifty-one papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño
  1. Chrysophanol delays aging via insulin/IGF-1 signaling pathway.
  2. Caenorhabditis elegans as a Screening Platform for Anti-aging Compounds.
  3. The Impact of Rosemary and Ginger Extracts on Aging and Healthspan in Drosophila.
  4. Association of α-Klotho with anti-aging effects of Ganoderma lucidum in animal models.
  5. The Nuclear-Mitochondrial Crosstalk in Aging: From Mechanisms to Therapeutics.
  6. The Mitochondria-Targeted Peptide Therapeutic Elamipretide Improves Cardiac and Skeletal Muscle Function During Aging Without Detectable Changes in Tissue Epigenetic or Transcriptomic Age.
  7. Unlocking Longevity in Aesthetic Dermatology: Epigenetics, Aging, and Personalized Care.
  8. Research progress on the anti-aging effect of polysaccharides of traditional Chinese medicine: Using Caenorhabditis elegans as an animal model.
  9. Design principles of gene circuits for longevity.
  10. Small extracellular vesicles from young adipose-derived stem cells ameliorate age-related changes in the heart of old mice.
  11. Cellular Senescence Is a Central Driver of Cognitive Disparities in Aging.
  12. A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan.
  13. Time-restricted feeding mitigates HFD-induced sarcopenic obesity in aging mice through improving the sensitivity of FGF21.
  14. Macrophage-targeting Antisenescence nanomedicine enables in-Situ NO induction for Gaseous and antioxidative atherosclerosis intervention.
  15. Comprehensive Bioinformatics Analysis Reveals Molecular Signatures and Potential Caloric Restriction Mimetics with Neuroprotective Effects: Validation in an In Vitro Stroke Model.
  16. Senolytic treatment for low back pain.
  17. Cordycepin's therapeutic potential: in vivo transport, transbilayer diffusion and anti-aging effects.
  18. Novel immunoinformatics-guided activation of CISD1 with compound 4'-methoxy-3',5,7-trihydroxyflavanone for the prevention of age-related cardiomyopathy.
  19. 27-Hydroxymangiferolic Acid Extends Lifespan and Improves Neurodegeneration in Caenorhabditis elegans by Activating Nuclear Receptors.
  20. AMP1-1 derived from Atractylodes macrocephala Koidz prevents bone aging triggered by lead and cadmium.
  21. Salvianolic acid B protects against UVB-induced HaCaT cell senescence and skin aging through NRF2 activation and ROS scavenging.
  22. Estropausal gut microbiota transplant improves measures of ovarian function in adult mice.
  23. Unlocking the therapeutic potential of gut microbiota for preventing and treating aging-related neurological disorders.
  24. Young fibroblast-derived migrasomes alleviate keratinocyte senescence and enhance wound healing in aged skin.
  25. Unveiling the geroprotective potential of Monarda didyma L.: insights from in vitro studies and a randomized clinical trial on slowing biological aging and improving quality of life.
  26. Topoisomerase inhibitor amonafide enhances defense responses to promote longevity in C. elegans.
  27. Fndc5/irisin mediates the benefits of aerobic exercise intervention on aging-associated sarcopenia in mice.
  28. Streptococcus thermophilus CNCM I-5570 lysate counteracts the aging process in human dermal fibroblast cells by neutralizing harmful free radicals and impacting antioxidant and anti-inflammatory pathways, thus restoring their physiological functions.
  29. Muscle-specific Keap1 deletion enhances force production but does not prevent inactivity-induced muscle atrophy in mice.
  30. Daytime-Restricted Feeding Alleviates D-Galactose-Induced Aging in Mice and Regulates the AMPK and mTORC1 Activities.
  31. Beyond pills and prescriptions: Exploring aging-related diseases with non-pharmacological strategies and molecular innovations.
  32. Anti-aging activities of an ethanolic extract of Lycium ruthenicum in Caenorhabditis elegans based on metabonomic analysis.
  33. Progress in the Application of Molecular Hydrogen in Medical Skin Cosmetology.
  34. Protective effects of Rosa roxburghii Tratt. extract against UVB-induced inflammaging through inhibiting the IL-17 pathway.
  35. Chronic treatment of old mice with AICAR reverses age-related changes in exercise performance and skeletal muscle gene expression.
  36. Lacticaseibacillus rhamnosus GG improves behavior, immune functions, and biological age markers in female mice with premature aging.
  37. Cognition on the move: Examining the role of physical exercise and neurogenesis in counteracting cognitive aging.
  38. Characterization and Anti-Aging Potency of Phenolic Compounds in Xianhu Tea Extracts.
  39. Associations Between Leisure-Time Physical Activity and Metabolomics-Based Markers of Biological Aging in Late Midlife: Short-Term and Long-Term Follow-Up.
  40. Long-term dietary allyl isothiocyanate, a TRPA1 agonist, ameliorates cardiac fibrosis and diastolic dysfunction in aged mice.
  41. Mushrooms in modern cosmetics: unlocking anti-aging, antioxidant, and therapeutic potential.
  42. Effectiveness of Extracellular Vesicle Application in Skin Aging Treatment and Regeneration: Do We Have Enough Evidence from Clinical Trials?
  43. Elevated urinary phytoestrogens are associated with delayed biological aging: a cross-sectional analysis of NHANES data.
  44. Mixtures of EGCG, bamboo leaf flavonoids, and broccoli seed water extracts exhibit anti-glycation and skin-protective effects.
  45. Influence of Klotho Protein Levels in Obesity and Sarcopenia: A Systematic Review.
  46. Development of a PLA Polymer-Based Liquid Filler for Next-Generation Aesthetics.
  47. Continuing the Legacy: Understanding and Reducing Tissue Aging to Prevent Many Currently Incurable Diseases.
  48. Polysaccharides with Arabinose: Key Players in Reducing Chronic Inflammation and Enhancing Immune Health in Aging.
  49. Exploring the mechanisms of cow placental peptides in delaying liver aging based on mitochondrial energy metabolism.
  50. Reversing Glycation with a Dietary Supplement Containing Rosemary Extract.
  51. Genetically supported targets and drug repurposing for brain aging: A systematic study in the UK Biobank.
  1. Free Radic Biol Med. 2025 Mar 12. pii: S0891-5849(25)00161-3. [Epub ahead of print]
    Chrysophanol delays aging via insulin/IGF-1 signaling pathway.
    Hongjiao Zhang, Jun Xiong, Qingyao Wang, Qiuyu Song, Lingjie Meng, Han Zhang, Yuxin Bao, Fang Liu, Yi Xiao.
      Aging is inevitable processes which play a significant role in the development of various diseases, including cardiovascular diseases, neurodegenerative disorders, and cancers. The extension of lifespan and the improvement of age-related diseases can potentially be achieved by targeting evolutionarily conserved pathways and mechanisms through pharmacological interventions. Chrysophanol (Chr), a naturally occurring anthraquinone compound primarily derived from rhubarb of the Polygonaceae family, exhibits a wide range of pharmacological activities, including anti-cancer, anti-inflammatory, and anti-bacterial effects. However, its role in regulating aging remains unclear. In this study, we discovered that Chr extends both lifespan and healthspan in Caenorhabditis elegans by activating the DAF-2/DAF-16 insulin signaling pathway. Furthermore, we observed that Chr promoted longevity in natural aging mice, doxorubicin-induced aging mice, and transgenic mice through the conserved Insulin/IGF-1 signaling pathway. Additionally, Chr also influenced senescence-associated secretory phenotypes (SASPs) and enhanced the expression of antioxidant genes, contributing to delayed aging. These findings highlight that Chr exerts anti-aging effects from C. elegans to mammals via the evolutionarily conserved Insulin/IGF-1 signaling pathway, positioning Chr as a promising candidate for the prevention and treatment of aging and age-related diseases.
    Keywords:  Aging; Chrysophanol; Insulin/IGF-1 signaling pathway; Lifespan
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.03.011
  2. Methods Mol Biol. 2025 ;2906 301-313
    Caenorhabditis elegans as a Screening Platform for Anti-aging Compounds.
    Eirini Mytilinaiou, Katerina Kitopoulou, Konstantinos Palikaras.
      As global life expectancy continues to rise, the need to understand and mitigate the effects of aging on human physiology has become increasingly important. Aging is characterized by cellular and functional decline, resulting in a higher prevalence of chronic diseases. Model organisms, such as Caenorhabditis elegans, provide valuable insights into the molecular mechanisms underlying aging and serve as platforms for developing potential therapeutic interventions. This chapter highlights the utility of C. elegans in aging research by presenting three straightforward protocols: the lifespan assay, thrashing assay, and lipofuscin accumulation assay. These assays are designed to effectively assess key physiological aspects of organismal health and provide a reliable framework for monitoring the aging process and evaluating anti-aging compounds. Here, we demonstrate the application of these protocols using Urolithin A as an example, underscoring their efficacy in advancing our understanding of aging and contributing to the development of potential interventions.
    Keywords:  Aging; Anti-aging compounds; Body bending; Caenorhabditis elegans; Lifespan; Lipofuscin; Nematode; Thrashing
    DOI:  https://doi.org/10.1007/978-1-0716-4426-3_18
  3. Aging Dis. 2025 Mar 07.
    The Impact of Rosemary and Ginger Extracts on Aging and Healthspan in Drosophila.
    Ricardo Aparicio, Anna M Salazar, Edward T Schmid, Armen Khanbabaei, Arun Rajgopal, R Keith Randolph, David W Walker.
      Aging leads to a decline in physiological functions and increased risk of mortality, yet therapeutic avenues are limited. Dietary phytochemicals provide an attractive approach to counteract age-related health decline. Here, we have examined the impact of feeding extracts of rosemary and ginger, prepared via three different extraction methods, on markers of aging and healthspan in the fruit fly Drosophila. We observed that certain, but not all, extracts of ginger produce modest prolongevity effects. Feeding extracts of rosemary, produced via the three different methods, each produced prolongevity effects. We observe that feeding combinations of both rosemary and ginger extracts leads to robust lifespan extension. We find that the prolongevity effects of rosemary and ginger extracts are linked to improved intestinal barrier function in aged flies. Importantly, we show that the anti-aging effects observed are not linked to reduced food intake. Interestingly, we observe several instances where the combination of rosemary plus ginger produces effects which are more pronounced or not seen for either extract alone. In terms of cellular hallmarks of aging, rosemary plus ginger feeding leads to AMPK activation and improved markers of autophagy and proteostasis in aged flies. Furthermore, feeding the combination of rosemary plus ginger feeding improves cognitive function in aged flies. Our results demonstrate that rosemary and ginger extracts can counteract aging and prolong healthspan in flies.
    DOI:  https://doi.org/10.14336/AD.2024.1558
  4. J Ethnopharmacol. 2025 Mar 07. pii: S0378-8741(25)00281-8. [Epub ahead of print]345 119597
    Association of α-Klotho with anti-aging effects of Ganoderma lucidum in animal models.
    Xiaojing Liu, Jiamin Zhao, Jia Liu, Yan Huang, Wei Deng, Luwen Yan, Ming Cui, Xinhua Pan, Huiwen Xiao, Xingzhong Liu.
       ETHNOPHARMACOLOGICAL RELEVANCE: Aging is a complex, universal process characterized by structural and functional decline across multiple organs. Ganoderma lucidum (G. lucidum), a renowned traditional Chinese medicinal fungus, has long been recognized for its anti-aging properties. However, the underlying mechanisms remain incompletely understood.
    AIM OF THE STUDY: This study aimed to investigate the anti-aging effects of G. lucidum and its underlying mechanisms.
    MATERIALS AND METHODS: We investigated the anti-aging effects of G. lucidum sporoderm-broken spore powder (Gl-SBSP) on Caenorhabditis elegans (C. elegans) lifespan and aging across multiple organs using natural aging, D-galactose (D-gal)-induced aging, and radiation-induced premature senescence mouse models. In C. elegans, we assessed lifespan, reproductive capacity, body length, pharyngeal pumping, body bends, fat and lipofuscin levels, as well as reactive oxygen species (ROS) accumulation. In mice, histopathological staining, complete blood counts, and enzyme-linked immunosorbent assay (ELISA) were used to evaluate tissue damage, while quantitative real-time PCR (RT-qPCR) was employed to access small intestine barrier integrity. Western blot (WB) and immunohistochemistry (IHC) were utilized to analyze the distribution of alpha Klotho (α-Klotho) in the kidney, blood, and urine.
    RESULTS: Gl-SBSP significantly extended C. elegans lifespan, improved reproductive capacity and mobility, and reduced lipofuscin and ROS levels. In naturally aged mice, Gl-SBSP enhanced physical appearance and performance. Additionally, Gl-SBSP alleviated aging-related structural and functional decline in multiple organs, including the colon, spleen, kidneys, liver, and small intestine, across all aging models. Biochemical analyses revealed that Gl-SBSP increased transmembrane α-Klotho (mα-Klotho) and soluble α-Klotho (sα-Klotho) levels in kidney tissue and elevated sα-Klotho levels in serum and urine.
    CONCLUSION: This study is the first to demonstrate that G. lucidum exerts α-Klotho-associated anti-aging effects in animal models, highlighting its potential as an anti-aging intervention.
    Keywords:  Aging; Aging mouse model; Functional decline; Ganoderma lucidum; α-Klotho
    DOI:  https://doi.org/10.1016/j.jep.2025.119597
  5. Free Radic Biol Med. 2025 Mar 12. pii: S0891-5849(25)00162-5. [Epub ahead of print]
    The Nuclear-Mitochondrial Crosstalk in Aging: From Mechanisms to Therapeutics.
    Yifei Feng, Yan Lu.
      Aging is a complex physiological process characterized by an irreversible decline in tissue and cellular functions, accompanied by an increased risk of age-related diseases, including neurodegenerative, cardiovascular, and metabolic disorders. Central to this process are epigenetic modifications, particularly DNA methylation, which regulate gene expression and contribute to aging-related epigenetic drift. This drift is characterized by global hypomethylation and localized hypermethylation, impacting genomic stability and cellular homeostasis. Simultaneously, mitochondrial dysfunction, a hallmark of aging, manifests as impaired oxidative phosphorylation, excessive reactive oxygen species production, and mitochondrial DNA mutations, driving oxidative stress and cellular senescence. Emerging evidence highlights a bidirectional interplay between epigenetics and mitochondrial function. DNA methylation modulates the expression of nuclear genes governing mitochondrial biogenesis and quality control, while mitochondrial metabolites, such as acetyl-CoA and S-adenosylmethionine, reciprocally influence epigenetic landscapes. This review delves into the intricate nuclear-mitochondrial crosstalk, emphasizing its role in aging-related diseases and exploring therapeutic avenues targeting these interconnected pathways to counteract aging and promote health span extension.
    Keywords:  Aging; DNA Methylation; Epigenetics; Mitochondrial Dysfunction
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.03.012
  6. Aging Cell. 2025 Mar 13. e70026
    The Mitochondria-Targeted Peptide Therapeutic Elamipretide Improves Cardiac and Skeletal Muscle Function During Aging Without Detectable Changes in Tissue Epigenetic or Transcriptomic Age.
    Wayne Mitchell, Gavin Pharaoh, Alexander Tyshkovskiy, Matthew Campbell, David J Marcinek, Vadim N Gladyshev.
      Aging-related decreases in cardiac and skeletal muscle function are strongly associated with various comorbidities. Elamipretide (ELAM), a novel mitochondria-targeted peptide, has demonstrated broad therapeutic efficacy in ameliorating disease conditions associated with mitochondrial dysfunction across both clinical and pre-clinical models. Herein, we investigated the impact of 8-week ELAM treatment on pre- and post-measures of C57BL/6J mice frailty, skeletal muscle, and cardiac muscle function, coupled with post-treatment assessments of biological age and affected molecular pathways. We found that health status, as measured by frailty index, cardiac strain, diastolic function, and skeletal muscle force, is significantly diminished with age, with skeletal muscle force changing in a sex-dependent manner. Conversely, ELAM mitigated frailty accumulation and was able to partially reverse these declines, as evidenced by treatment-induced increases in cardiac strain and muscle fatigue resistance. Despite these improvements, we did not detect statistically significant changes in gene expression or DNA methylation profiles indicative of molecular reorganization or reduced biological age in most ELAM-treated groups. However, pathway analyses revealed that ELAM treatment showed pro-longevity shifts in gene expression, such as upregulation of genes involved in fatty acid metabolism, mitochondrial translation, and oxidative phosphorylation, and downregulation of inflammation. Together, these results indicate that ELAM treatment is effective at mitigating signs of sarcopenia and cardiac dysfunction in an aging mouse model, but that these functional improvements occur independently of detectable changes in epigenetic and transcriptomic age. Thus, some age-related changes in function may be uncoupled from changes in molecular biological age.
    Keywords:  aging; aging biomarkers; cardiac dysfunction; elamipretide; epigenetic clocks; mitochondria; transcriptomic clocks
    DOI:  https://doi.org/10.1111/acel.70026
  7. Int J Dermatol. 2025 Mar 10.
    Unlocking Longevity in Aesthetic Dermatology: Epigenetics, Aging, and Personalized Care.
    Diala Haykal, Frederic Flament, Pascale Mora, Guive Balooch, Hugues Cartier.
      The concept of aging has evolved from being primarily attributed to genetic factors to recognizing the critical role of epigenetic mechanisms. Recent advancements, such as epigenetic clocks, have provided tools to assess biological age and offer insights into aging processes at the molecular level. In aesthetic dermatology, understanding these processes allows for more personalized, effective interventions targeting the root causes of skin aging. This review explores the interplay of epigenetic changes, aging, and the potential of personalized care to enhance longevity and skin rejuvenation. This review is based on an extensive literature search conducted across PubMed and other scientific databases. Studies focused on epigenetic mechanisms such as DNA methylation, histone modifications, and their relationship to skin aging. Particular attention was given to recent advancements in biological clocks, including Horvath's Clock and GrimAge, and their implications for personalized dermatological treatments. Epigenetic clocks, such as Horvath's Clock, have demonstrated utility in assessing biological age through methylation markers, revealing actionable insights into aging processes. Energy-based devices like fractional lasers and radiofrequency have shown promise in reversing age-related epigenetic changes, promoting collagen synthesis, and reducing biological skin age. Additionally, lifestyle factors such as diet, sleep, and circadian rhythm alignment significantly influence epigenetic aging and skin health. Integrating epigenetic insights into aesthetic dermatology represents a paradigm shift in skin rejuvenation, allowing for personalized treatments that address visible signs of aging and underlying molecular mechanisms. Using biological clocks provides a framework for tailoring interventions to individual patient needs, optimizing outcomes, and extending the longevity of aesthetic results. Future research should focus on longitudinal studies, accessibility, and ethical considerations to fully harness the potential of epigenetics in promoting skin health and overall well-being.
    Keywords:  biological aging; clinical dermatology; cosmetic dermatology; education; epigenetic clocks; longevity; personalized aesthetic treatments; skin rejuvenation
    DOI:  https://doi.org/10.1111/ijd.17725
  8. FASEB J. 2025 Mar 31. 39(6): e70454
    Research progress on the anti-aging effect of polysaccharides of traditional Chinese medicine: Using Caenorhabditis elegans as an animal model.
    Jiazi Lin, Jiamin Yu, Xiao Wang, Ruixiang Shi, Yefang Liang, Jianhua Li, Tong Zhou, Chengkai Chen, Xiaodong Duan, Yongan Deng, Simin Yang, Shuting Zeng, Xuejuan Shen, Xiangyu Chen, Yi Wang, Guibo Sun, Zunpeng Shu.
      With the growing elderly population and increasing incidence of various aging-related diseases, the scientific community is faced with an urgent challenge to identify natural anti-aging agents. Traditional Chinese medicine (TCM) polysaccharides have been proven to have good anti-aging activities. This article reviews the literature on the anti-aging pathways of traditional Chinese medicine polysaccharides applied to Caenorhabditis elegans models in the past decade. In our study, we found that 45 TCM polysaccharides from 28 genera and 26 families could delay the aging process of C. elegans. Traditional Chinese medicine polysaccharides delay the aging of C. elegans mainly by anti-oxidative stress, eliminating free radicals, repairing DNA damage, and insulin/insulin-like growth factor signaling pathway (IIS signaling pathway). In addition, an increasing number of traditional Chinese medicine polysaccharides have been found to prolong the lifespan of C. elegans by reducing inflammation, regulating intestinal flora, and affecting immune cell function. In this paper, C. elegans was used as an animal model to clarify the anti-aging pathway of traditional Chinese medicine polysaccharides, so as to provide theoretical guidance for future research and clinical experiments on the anti-aging effect of traditional Chinese medicine polysaccharides.
    Keywords:   Caenorhabditis elegans ; IIS signaling pathway; anti‐aging; oxidative stress; traditional Chinese medicine polysaccharides
    DOI:  https://doi.org/10.1096/fj.202403250RR
  9. Trends Cell Biol. 2025 Mar 12. pii: S0962-8924(25)00040-6. [Epub ahead of print]
    Design principles of gene circuits for longevity.
    Paula Godoy, Nan Hao.
      Aging is a dynamic process that is driven by cellular damage and disruption of homeostatic gene regulatory networks (GRNs). Traditional studies often focus on individual genes, but understanding their interplay is key to unraveling the mechanisms of aging. This review explores the gene circuits that influence longevity and highlights the role of feedback loops in maintaining cellular balance. The SIR2-HAP circuit in yeast serves as a model to explore how mutual inhibition between pathways influences aging trajectories and how engineering stable fixed points or oscillations within these circuits can extend lifespan. Feedback loops crucial for maintaining homeostasis are also reviewed, and we highlight how their destabilization accelerates aging. By leveraging systems and synthetic biology, strategies are proposed that may stabilize these loops within single cells, thereby enhancing their resilience to aging-related damage.
    Keywords:  aging; computational modeling; feedback loops; gene regulatory networks; synthetic biology; systems biology
    DOI:  https://doi.org/10.1016/j.tcb.2025.02.006
  10. Stem Cell Res Ther. 2025 Mar 13. 16(1): 138
    Small extracellular vesicles from young adipose-derived stem cells ameliorate age-related changes in the heart of old mice.
    Jorge Sanz-Ros, Javier Huete-Acevedo, Cristina Mas-Bargues, Nekane Romero-García, Mar Dromant, Michel van Weeghel, Georges E Janssens, Consuelo Borrás.
       BACKGROUND: Aging entails a progressive decline in physiological functions, elevating the risk of age-related diseases like heart failure or aortic stenosis. Stem cell therapies, especially those that use paracrine signaling, can potentially mitigate the adverse effects of aging.
    OBJECTIVES: The objective is to explore the potential of small extracellular vesicles (sEVs) derived from young adipose-derived stem cells (ADSC-sEVs) in reversing structural, molecular, and functional changes associated with aging in the heart.
    METHODS: Aged C57BL/6J mice were treated intravenously with ADSC-sEVs from young mice or PBS as controls. Young mice were included to identify specific age-associated changes. The impact of sEV treatment on cardiac function was assessed using transthoracic echocardiography and physical endurance tests. Histological and molecular analyses were conducted on heart tissue to evaluate structural changes and markers of senescence, inflammation, and oxidative stress. A comprehensive metabolomic analysis was also performed on heart tissues to identify changes in metabolic profiles associated with aging and treatment status.
    RESULTS: The administration of ADSC-sEVs significantly improves several aging-associated cardiac parameters, including oxidative stress, inflammation, and cellular senescence reductions. We also report on the age-related reversal of myocardial structure and function changes, highlighted by decreased fibrosis and improved vascularization. Notably, echocardiographic assessments reveal that sEV treatments ameliorate diastolic dysfunction and left ventricle structural alterations typically associated with aging. Furthermore, the treatment shifts the heart metabolome towards a more youthful profile.
    CONCLUSIONS: These results denote the potential of ADSC-sEVs as a novel, noninvasive therapeutic strategy for mitigating cardiac aging-associated functional decline.
    Keywords:  Aging; Extracellular vesicles; Heart failure; Inflammation; Metabolomics; Regenerative medicine
    DOI:  https://doi.org/10.1186/s13287-025-04255-z
  11. Aging Cell. 2025 Mar 12. e70041
    Cellular Senescence Is a Central Driver of Cognitive Disparities in Aging.
    Matthew P Baier, Rojina Ranjit, Daniel B Owen, Jenna L Wilson, Megan A Stiles, Anthony M Masingale, Zachary Thomas, Anne Bredegaard, David M Sherry, Sreemathi Logan.
      Cognitive function in aging is heterogeneous: while some older individuals develop significant impairments and dementia, others remain resilient and retain cognitive function throughout their lifespan. The molecular mechanisms that underlie these divergent cognitive trajectories, however, remain largely unresolved. Here, we utilized a high-resolution home-cage-based cognitive testing paradigm to delineate mechanisms that contribute to age-related cognitive heterogeneity. We cognitively stratified aged C57Bl/6N male mice by cognitive performance into intact (resilient) or impaired subgroups based on young performance benchmarks. Cognitively impaired males exhibited marked reactive gliosis in the hippocampus, characterized by microglial activation, increased astrocyte arborization, and elevated transcriptional expression of reactivity markers. These changes were accompanied by increased markers of cellular senescence and the associated senescence-associated secretory phenotype (SASP) in impaired animals, including p16INK4a, SASP factors (e.g., Il-6, Il-1b, Mmp3), and SA-β-gal staining in the hippocampus. Notably, clearance of senescent cells using senolytic agents dasatinib and quercetin ameliorated the heterogeneity in cognitive performance observed with age and attenuated impairment-associated gliosis, senescence markers, and mitochondrial dysfunction. Aged female mice could not be stratified into subgroups yet showed increased neuroinflammation with age that was not resolved with senolytics. Collectively, our findings implicate cellular senescence as a central driver of sex-specific neuroinflammation that drives divergent cognitive trajectories in aging. Thus, we demonstrate that senolytic treatment is an effective therapeutic strategy to mitigate cognitive impairment by reducing neuroinflammation and associated metabolic disturbances.
    Keywords:  cellular senescence; cognitive heterogeneity; dementia; neuroinflammation; reactive gliosis; senolytic
    DOI:  https://doi.org/10.1111/acel.70041
  12. Nat Aging. 2025 Mar 07.
    A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan.
    Lorna Jayne, Aurora Lavin-Peter, Julian Roessler, Alexander Tyshkovskiy, Mateusz Antoszewski, Erika Ren, Aleksandar Markovski, Senmiao Sun, Hanqi Yao, Vijay G Sankaran, Vadim N Gladyshev, Robert T Brooke, Steve Horvath, Eric C Griffith, Sinisa Hrvatin.
      Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms of how torpor affects aging, and whether hypothermic and hypometabolic states can be induced to slow aging and increase healthspan, remain unknown. Here we demonstrate that the activity of a spatially defined neuronal population in the preoptic area, which has previously been identified as a torpor-regulating brain region, is sufficient to induce a torpor-like state (TLS) in mice. Prolonged induction of TLS slows epigenetic aging across multiple tissues and improves healthspan. We isolate the effects of decreased metabolic rate, long-term caloric restriction, and decreased core body temperature (Tb) on blood epigenetic aging and find that the decelerating effect of TLSs on aging is mediated by decreased Tb. Taken together, our findings provide novel mechanistic insight into the decelerating effects of torpor and hibernation on aging and support the growing body of evidence that Tb is an important mediator of the aging processes.
    DOI:  https://doi.org/10.1038/s43587-025-00830-4
  13. J Nutr Biochem. 2025 Mar 05. pii: S0955-2863(25)00056-7. [Epub ahead of print] 109893
    Time-restricted feeding mitigates HFD-induced sarcopenic obesity in aging mice through improving the sensitivity of FGF21.
    Ting Wang, Hongkun Lin, Yan Deng, Wenwen Chen, Yangliu Xu, Li Wang, Aojia Zhou, Yidan Zhang, Ziping Wang, Xin Jin, Li Zhang, Xin Wang, Yang Zhou, Ruhan Wang, Shuang Rong.
      Time-restricted feeding (TRF) is a dietary intervention that has been shown to have numerous health benefits. However, it is important to further investigate the potential effectiveness of TRF in addressing sarcopenic obesity (SO), which is characterized by a combination of age-related obesity and sarcopenia. In this study, 14-month-old C57BL/6J male mice were fed either regular chow diet or high-fat diet (HFD), and had either ad libitum or restricted access to food for 8 hours daily (Intervention for 7 months). For the human trial (ChiCTR2100052876), obese individuals (n=21) with a Body Mass Index ≥28 were recruited and instructed to adopt an 8-hour eating window and a 16-hour fasting period. Here, we found that the TRF intervention significantly reduced global fat mass (p<0.001) and volume (p<0.05), and increase lean mass compared to mice fed with HFD. Furthermore, TRF improved overall metabolic mobility (8h TRF+HFD vs. AL+HFD). This intervention also enhanced liver FGF21 protein levels (p<0.01) and the expression of FGFR1 and FGF21 target genes in adipose and muscle tissues, thus improving mitochondrial quality control in these tissues. Notably, TRF interventions led to a significant decrease in serum FGF21 levels (p<0.05). In the human trial, TRF intervention resulted in a significant reduction in weight (p<0.001) and body fat levels (p<0.001) among obese individuals, as well as a decrease in serum GLU (p<0.001), insulin (p<0.001), and TC levels (p<0.05). Overall, the findings indicate that TRF intervention improves SO by regulating liver FGF21 expression, thereby enhancing FGF21 sensitivity in adipose and muscle tissues.
    Keywords:  FGF21; Time-restricted feeding/eating; aging; sarcopenic obesity
    DOI:  https://doi.org/10.1016/j.jnutbio.2025.109893
  14. Bioact Mater. 2025 Jun;48 294-312
    Macrophage-targeting Antisenescence nanomedicine enables in-Situ NO induction for Gaseous and antioxidative atherosclerosis intervention.
    Yuanyuan Peng, Wei Feng, Hui Huang, Yu Chen, Shaoling Yang.
      Senescent-endothelial cells significantly accelerate atherosclerosis progression, making the mitigation of cellular aging a promising strategy for treating the disease. Nitric oxide (NO), a low molecular weight and lipophilic gas, has been shown to penetrate cell membranes effectively and delay cell senescence. In this study, we designed and engineered osteopontin (OPN)-modified nanoliposomes (CZALO) that encapsulate L-arginine (L-Arg) and cerium-zirconium oxide nanoparticles (CZ NPs), which exhibit enzyme-like activities for targeted atherosclerosis treatment. Following inflammatory chemotaxis and OPN-mediated internalization by macrophages, CZ NPs released from CZALO nanoliposomes significantly scavenge reactive oxygen species, thereby inhibiting cholesterol uptake and promoting macrophage phenotypic transformation, resulting in both antioxidant and anti-inflammatory effects. Additionally, nitric oxide synthase (NOS) overexpressed in macrophages catalyzes L-Arg to produce NO, which is then selectively released in situ and diffuses into endothelial cells, exerting anti-aging effects by regulating senescence-associated secretory phenotype factor secretion, enhancing lysosomal function, alleviating cell cycle arrest, and reducing DNA damage. The antioxidant and anti-aging effects of CZALO nanoliposomes collectively alleviate atherosclerotic burden with minimal toxicity both in vitro and in vivo. This "two-birds-one-stone" nanotherapeutic offers a novel approach for regulating vascular microenvironment homeostasis and improving therapeutic efficiency in atherosclerosis treatment.
    Keywords:  Anti-inflammation; Anti-senescence; Antioxidation; Atherosclerosis; Nanozyme
    DOI:  https://doi.org/10.1016/j.bioactmat.2025.02.025
  15. J Mol Neurosci. 2025 Mar 13. 75(1): 32
    Comprehensive Bioinformatics Analysis Reveals Molecular Signatures and Potential Caloric Restriction Mimetics with Neuroprotective Effects: Validation in an In Vitro Stroke Model.
    Navami Krishna, Neelakandan Annamalai Ramalakshmi, Rajanikant Golgodu Krishnamurthy.
      Caloric restriction (CR) is a dietary intervention that reduces calorie intake without inducing malnutrition, demonstrating lifespan-extending effects in preclinical studies and some human trials, along with potential benefits in ameliorating age-related ailments. Caloric restriction mimetics (CRMs) are compounds mimicking CR effects, offering a potential therapeutic avenue for age-related diseases. This study explores the potential protective effects of CR on the brain neocortex (GSE11291) and the identification of CRMs using integrative bioinformatics and systems biology approaches. Our findings indicate that long-term CR activates cellular pathways improving mitochondrial function, enhancing antioxidant capacity, and reducing inflammation, potentially providing neuroprotection. The key signaling pathways enriched in our study include PPAR, mTOR, FoxO, AMPK, and Notch signaling pathways, which are crucial regulators of metabolism, cellular stress response, neuroprotection, and longevity. We identify key signaling molecules and molecular mechanisms associated with CR, including transcription factors, kinase regulators, and microRNAs linked to differentially expressed genes. Furthermore, potential CRMs such as rapamycin, replicating CR-related health benefits, are identified. Additionally, machine learning models were developed to classify small molecules based on their CNS activity and anti-inflammatory properties. As a proof of concept, we have demonstrated the ischemic neuroprotective effects of two top-ranked candidate reference molecules (CRMs) using the oxygen-glucose deprivation (OGD) model, an established in vitro stroke model. However, further investigations are essential to fully elucidate the therapeutic potential of these CRMs. In summary, our study suggests that long-term CR entails protective mechanisms preserving and safeguarding neuronal function, potentially impacting the treatment of age-related neurological diseases. Moreover, our findings contribute to the identification of potential genes and regulatory molecules involved in CR, along with potential CRMs, providing a promising foundation for future research in the field of neurological disorder treatment.
    Keywords:  Caloric restriction mimetics; Differentially expressed genes; Ischemic stroke; Machine learning; Neuronal protection; Oxygen–glucose deprivation model
    DOI:  https://doi.org/10.1007/s12031-025-02328-5
  16. Sci Adv. 2025 Mar 14. 11(11): eadr1719
    Senolytic treatment for low back pain.
    Matthew Mannarino, Hosni Cherif, Saber Ghazizadeh, Oliver Wu Martinez, Kai Sheng, Elsa Cousineau, Seunghwan Lee, Magali Millecamps, Chan Gao, Alice Gilbert, Cedric Peirs, Reza Sharif Naeini, Jean A Ouellet, Laura S Stone, Lisbet Haglund.
      Senescent cells (SnCs) accumulate because of aging and external cellular stress throughout the body. They adopt a senescence-associated secretory phenotype (SASP) and release inflammatory and degenerative factors that actively contribute to age-related diseases, such as low back pain (LBP). The senolytics, o-vanillin and RG-7112, remove SnCs in human intervertebral discs (IVDs) and reduce SASP release, but it is unknown whether they can treat LBP. sparc-/- mice, with LBP, were treated orally with o-vanillin and RG-7112 as single or combination treatments. Treatment reduced LBP and SASP factor release and removed SnCs from the IVD and spinal cord. Treatment also lowered degeneration scores in the IVDs, improved vertebral bone quality, and reduced the expression of pain markers in the spinal cord. Together, our data suggest RG-7112 and o-vanillin as potential disease-modifying drugs for LBP and other painful disorders linked to cell senescence.
    DOI:  https://doi.org/10.1126/sciadv.adr1719
  17. J Sci Food Agric. 2025 Mar 14.
    Cordycepin's therapeutic potential: in vivo transport, transbilayer diffusion and anti-aging effects.
    Xiaoliang Zhang, Sijia Wu, Qihan Huang, Shubo Jing, Pang Yong, Ling Zhang, Hong Zhuang.
       BACKGROUND: Cordycepin (3'-deoxyadenosine) is a bioactive compound known for its numerous beneficial properties, including antioxidant, anti-aging and antitumor effects. Despite its promising therapeutic potential, the in vivo transport mechanisms of cordycepin remain inadequately understood. Previous studies have highlighted its biological activity, but there is limited information regarding its transport and distribution, as well as how it interacts with biological systems to exert these effects. The present study explored the transport mechanisms of cordycepin, specifically its interaction with bovine serum albumin (BSA) transporters and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, and assessed its anti-aging effects through cellular experiments.
    RESULTS: The study demonstrates that cordycepin effectively interacts with DPPC liposomes, improving its therapeutic efficacy. Spectral analysis shows strong binding between cordycepin and transporters, aiding its distribution in the bloodstream and targeted accumulation in tissues. Additionally, cellular tests reveal that cordycepin inhibits butyl hydroperoxide-induced cellular senescence in a dose-dependent manner.
    CONCLUSION: The interaction of cordycepin with BSA transporters and DPPC liposomes enhances its distribution and therapeutic potential. The compound also shows promise as an anti-aging agent by reducing cellular senescence. These findings provide insight into cordycepin's in vivo behavior and suggest strategies to enhance its pharmacological effectiveness. © 2025 Society of Chemical Industry.
    Keywords:  anti‐aging; biological membranes; cordycepin; transporter protein
    DOI:  https://doi.org/10.1002/jsfa.14220
  18. Biogerontology. 2025 Mar 11. 26(2): 68
    Novel immunoinformatics-guided activation of CISD1 with compound 4'-methoxy-3',5,7-trihydroxyflavanone for the prevention of age-related cardiomyopathy.
    Abdur-Rehman Munir, Javed Iqbal Wattoo, Kaniz Fatima, Kubra Ilyas.
      Aging is a principal driver of cardiomyopathy, characterized by mitochondrial dysfunction, oxidative stress, and progressive telomere shortening in cardiomyocytes. These pathological changes impair cellular bioenergetics and regenerative capacity, accelerating cardiac deterioration. However, targeted interventions to mitigate these effects remain limited. This research investigates the therapeutic potential of CISD1 activation as a novel strategy to counteract aging-associated cardiac decline. Using advanced Immunoinformatic approaches, including molecular docking, protein structure modelling, and molecular dynamics simulations, we assess the role of CISD1 upregulation in enhancing mitochondrial bioenergetics, reducing oxidative stress, and preserving telomere integrity. Our Immunoinformatic findings reveal that CISD1 activation stabilizes mitochondrial function, mitigates oxidative damage, and slows telomere attrition, thereby sustaining cardiomyocyte function and delaying cellular senescence. Our research identifies 4'-Methoxy-3', 5,7-trihydroxy flavanone as a potential small-molecule activator of CISD1, offering a promising pharmacological approach to modulate mitochondrial dynamics in aging cardiomyocytes. By directly addressing the mechanistic link between CISD1, mitochondrial stability, and telomere preservation, this research bridges a critical gap in understanding age-related cardiomyopathy and provides a foundation for targeted therapeutic interventions. Our findings suggest that CISD1 activation could restore cellular homeostasis in aged cardiac tissues, reducing the risk of heart failure and other aging-related cardiovascular diseases. These insights advance age-related disease intervention strategies by targeting fundamental molecular pathways involved in cardiomyocyte aging.
    Keywords:  Age-related cardiovascular disease; CISD1 activation; Cardiomyopathy; Mitochondrial bioenergetics; Telomere preservation
    DOI:  https://doi.org/10.1007/s10522-025-10211-4
  19. Molecules. 2025 Feb 21. pii: 1010. [Epub ahead of print]30(5):
    27-Hydroxymangiferolic Acid Extends Lifespan and Improves Neurodegeneration in Caenorhabditis elegans by Activating Nuclear Receptors.
    Xiaoyan Gao, Jing Yu, Yin Li, Hang Shi, Lijun Zhang, Minglv Fang, Ying Liu, Cheng Huang, Shengjie Fan.
      27-Hydroxymangiferolic acid (27-HMA) is a naturally occurring compound in mango fruits that exhibits diverse biological functions. Here, we show that 27-HMA activates the transcriptional activity of farnesoid X receptor (FXR), a nuclear receptor transcription factor, extending the lifespan and healthspan in Caenorhabditis elegans (C. elegans). Meanwhile, the longevity-promoting effect of 27-HMA was attenuated in the mutants of nhr-8 and daf-12, the FXR homologs, indicating that the longevity effects of 27-HMA in C. elegans may depend on nuclear hormone receptors (NHRs). Further analysis revealed potential associations between the longevity effects of 27-HMA and the insulin/insulin-like growth factor-1 signaling (IIS)/TORC1 pathway. Moreover, 27-HMA increased the toxin resistance of nematodes and activated the expression of detoxification genes, which rely on NHRs. Finally, 27-HMA improved the age-related neurodegeneration in Alzheimer's disease (AD) and Parkinson's disease (PD) C. elegans models. Taken together, our findings suggest that 27-HMA is a novel FXR agonist and may prolong lifespan and healthspan via activating NHRs.
    Keywords:  27-hydroxymangiferolic acid; Alzheimer’s disease; Parkinson’s disease; detoxification; lifespan; nuclear receptor
    DOI:  https://doi.org/10.3390/molecules30051010
  20. Comp Biochem Physiol C Toxicol Pharmacol. 2025 Mar 11. pii: S1532-0456(25)00070-5. [Epub ahead of print] 110189
    AMP1-1 derived from Atractylodes macrocephala Koidz prevents bone aging triggered by lead and cadmium.
    Jinpeng Wang, Yu Jiang, Xiaoyu Hou, Raza Tahir, Yiping He, Xinyue Liu, Defeng Xing, Lijun Wei.
      As the major pollutants of industrial wastewater, lead (Pb) and cadmium (Cd) contaminate the environment and lead to bone aging when combined. To elucidate the potential mechanism by which Pb and Cd accelerate bone aging and to screen effective protective agents, we determined the optimum concentrations of Pb and Cd to establish the aging models in vitro and in vivo. The successful establishment of aging models was confirmed through β-galactosidase (β-gal) staining, the detection of aging markers, and the evaluation of biomechanical parameters. Subsequently, the polysaccharides were extracted separately from seven plants and Atractylodes macrocephala polysaccharide (AMP) was confirmed to have the strongest effect on osteoblast proliferation. Therefore, we purified AMP to obtain a small molecular fragment called AMP1-1 and investigated its effect. It has been revealed that AMP1-1 could resist oxidative stress and promote the proliferation and differentiation of osteoblasts, thereby slowing apoptosis and alleviating cell senescence through the results of the β-gal staining and the analyses of the osteoblastic, antioxidant, apoptotic, and senescence indexes. The results in vivo suggested that AMP1-1 exerted a protective role in bone aging by inhibiting the above pathways. Consequently, AMP1-1 has theoretical significance for further development of biological protective agents against heavy metal pollution.
    Keywords:  Apoptosis; Atractylodes macrocephala polysaccharide1-1; Bone aging; Cadmium; Lead; Oxidative stress
    DOI:  https://doi.org/10.1016/j.cbpc.2025.110189
  21. J Photochem Photobiol B. 2025 Mar 01. pii: S1011-1344(25)00042-9. [Epub ahead of print]266 113139
    Salvianolic acid B protects against UVB-induced HaCaT cell senescence and skin aging through NRF2 activation and ROS scavenging.
    Jia-Ming Sun, Yu-Xin Liu, Yi-Tung Tsai, Yang-Dan Liu, Chia-Kang Ho, Dong-Sheng Wen, Ting-Yu Tsai, Dan-Ning Zheng, Ya Gao, Yi-Fan Zhang, Li Yu.
       BACKGROUND: Prolonged sunlight exposure can cause skin photoaging. The epidermis, the outermost layer of the skin, protects the body from the environment. This study explored the protective effect of salvianolic acid B (Sal-B), a bioactive compound from Salvia miltiorrhiza, against photoaging and examined its specific mechanism.
    METHODS: In vitro, HaCaT cells were treated with various doses of Sal-B before ultraviolet B (UVB) light exposure. Assessments in HaCaT cells included cellular senescence, apoptotic cell ratio, reactive oxygen species (ROS) levels, mitochondrial function, superoxide dismutase activity, and gene and protein expression. Immunofluorescence labeling, nuclear factor erythroid 2-related factor 2 (NRF2) knockdown, and Western blotting analysis were used. To assess Sal-B's protective effects on skin photoaging in vivo, we employed a nude mouse model and an ex vivo human skin model.
    RESULTS: In vitro, Sal-B significantly activated NRF2, scavenged ROS, protected mitochondrial function, and inhibited nuclear factor kappa B and mitogen-activated protein kinase pathways. Ultimately, Sal-B prevented UVB-induced photoaging and keratinocyte apoptosis. In vivo, we confirmed that Sal-B improved skin wrinkles and epidermal thickness in nude mice following UVB irradiation, displaying greater efficacy than tretinoin.
    CONCLUSION: We identified the preventive implications of Sal-B against UVB-induced senescence in skin photoaging and revealed its potential as a regulator of the NRF2 signaling pathway.
    Keywords:  Keratinocytes; NRF2; Sal-B; Skin aging
    DOI:  https://doi.org/10.1016/j.jphotobiol.2025.113139
  22. bioRxiv. 2025 Feb 26. pii: 2024.05.03.592475. [Epub ahead of print]
    Estropausal gut microbiota transplant improves measures of ovarian function in adult mice.
    Minhoo Kim, Justin Wang, Steven E Pilley, Ryan J Lu, Alan Xu, Younggyun Kim, Minying Liu, Xueyan Fu, Sarah L Booth, Peter J Mullen, Bérénice A Benayoun.
      Decline in ovarian function with age not only affects fertility but is also linked to a higher risk of age-related diseases in women ( e.g . osteoporosis, dementia). Intriguingly, earlier menopause is linked to shorter lifespan; however, the underlying molecular mechanisms of ovarian aging are not well understood. Recent evidence suggests the gut microbiota may influence ovarian health. In this study, we characterized ovarian aging associated microbial profiles in mice and investigated the effect of the gut microbiome from young and estropausal female mice on ovarian health through fecal microbiota transplantation. We demonstrate that the ovarian transcriptome can be broadly remodeled after heterochronic microbiota transplantation, with a reduction in inflammation-related gene expression and trends consistent with transcriptional rejuvenation. Consistently, these mice exhibited enhanced ovarian health and increased fertility. Using metagenomics-based causal mediation analyses and serum untargeted metabolomics, we identified candidate microbial species and metabolites that may contribute to the observed effects of fecal microbiota transplantation. Our findings reveal a direct link between the gut microbiota and ovarian health.
    DOI:  https://doi.org/10.1101/2024.05.03.592475
  23. Neuroscience. 2025 Mar 10. pii: S0306-4522(25)00221-0. [Epub ahead of print]
    Unlocking the therapeutic potential of gut microbiota for preventing and treating aging-related neurological disorders.
    Geetika Garg, Anchal Trisal, Abhishek Kumar Singh.
      Billions of microorganisms inhabit the human gut and maintain overall health. Recent research has revealed the intricate interaction between the brain and gut microbiota through the microbiota-gut-brain axis (MGBA) and its effect on neurodegenerative disorders (NDDs). Alterations in the gut microbiota, known as gut dysbiosis, are linked to the development and progression of several NDDs. Studies suggest that the gut microbiota may be a viable target for improving cognitive health and reducing hallmarks of brain aging. Numerous pathways including hypothalamic-pituitary-adrenal axis stimulation, neurotransmitter release disruption, system-wide inflammation, and increased intestinal and blood-brain barrier permeability connect gut dysbiosis to neurological conditions. Metabolites produced by the gut microbiota influence neural processes that affect brain function. Clinical interventions depend on the capacity to understand the equilibrium between beneficial and detrimental gut microbiota, as it affects both neurodegeneration and neuroprotection. The importance of the gut microbiota and its metabolites during brain aging and the development of neurological disorders is summarized in this review. Moreover, we explored the possible therapeutic effects of the gut microbiota on age-related NDDs. Highlighting various pathways that connect the gut and the brain, this review identifies several important domains where gut microbiota-based interventions could offer possible solutions for age-related NDDs. Furthermore, prebiotics and probiotics are discussed as effective alternatives for mitigating indirect causes of gut dysbiosis. These therapeutic interventions are poised to play a significant role in improving dysbiosis and NDDs, paving the way for further research.
    Keywords:  Blood-brain barrier; Brain aging; Gut microbiota; MGBA; Neurodegenerative disorders
    DOI:  https://doi.org/10.1016/j.neuroscience.2025.03.020
  24. J Nanobiotechnology. 2025 Mar 11. 23(1): 200
    Young fibroblast-derived migrasomes alleviate keratinocyte senescence and enhance wound healing in aged skin.
    Hanlin Tu, Yingliang Shi, Yi Guo, Zhongyang Zou, Yuyan He, Jing Zhou, Sangang He, Guoliang Sa.
       BACKGROUND: Alterations in intercellular communication driven by cellular senescence constitute an important factor in skin aging. Migrasome, a newly discovered vesicular organelle, efficiently participates in intercellular communication; however, the relationship between cellular senescence and migrasomes remains unreported.
    OBJECTIVE: This study aims to explore the possible relationship between cellular senescence and migrasomes formation, and investigate the effects of young fibroblast-derived migrasomes on senescent keratinocytes and wound healing in aged skin.
    RESULT: Single-cell RNA sequencing (scRNA-seq) data analysis revealed that fibroblasts exhibited the highest level of transcriptional variability during skin aging, and the degree of fibroblast senescence negatively correlated with the expression level of migrasome-associated markers. Further multiplex Immunohistochemistry (mIHC) results suggested that younger mouse skin contained more migrasomes than older mouse skin. Transmission electron microscopy (TEM) observations demonstrated abundant migrasomes in the skin from young individuals. In vitro experiments indicated that young fibroblasts produced significantly more migrasomes than senescent fibroblasts, as confirmed by wheat germ agglutinin (WGA) staining and scanning electron microscopy (SEM). Importantly, purified migrasomes from young fibroblasts were found to reduce the expression of senescence-associated markers in HaCaT cells. In vivo, using a wound healing model in naturally aged mice, we observed that migrasomes derived from young fibroblasts not only accelerated wound healing but also reduced senescence-associated marker expression in the skin.
    CONCLUSION: Migrasomes formation ability reduced during skin aging progress, and young fibroblast-derived migrasomes rejuvenated senescent keratinocytes and promoted wound healing in aged skin. These findings offer new ideas for alleviating skin aging and enhancing wound healing in aged skin.
    Keywords:  Aging; Fibroblast; Migrasomes; Senescence; Skin wound healing
    DOI:  https://doi.org/10.1186/s12951-025-03293-2
  25. Geroscience. 2025 Mar 10.
    Unveiling the geroprotective potential of Monarda didyma L.: insights from in vitro studies and a randomized clinical trial on slowing biological aging and improving quality of life.
    Manuela Campisi, Luana Cannella, Omar Paccagnella, Alessandra R Brazzale, Alberto Agnolin, Torsten Grothe, Julia Baumann, Sofia Pavanello.
      Aging is driven by fundamental mechanisms like oxidative stress, telomere shortening and changes in DNA methylation, which together prepare the ground for age-related diseases. Botanical extracts, rich in bioactive phytoconstituents, represent a promising resource for developing therapies that target these mechanisms to promote healthy aging. This study explores the geroprotective potential of Monarda didyma L. extract. In vitro analyses revealed the extract's strong antioxidant activity, ability to reduce telomere shortening, and capacity to protect against DNA damage, thereby decreasing cellular senescence and improving endothelial function. The randomized, double-blind clinical trial demonstrated that daily oral supplementation with the extract significantly improved leukocyte telomere length (LTL) and stabilized DNA methylation age (DNAmAge) in the intervention group, while the placebo group experienced accelerated epigenetic aging and hypermethylation of critical age-related genes (ELOVL2 and FHL2). The intervention group also reported enhanced quality of life, particularly in the physical domain, along with improved movement and quality sleep indices detected by questionnaire and wearable sensors. These compelling findings position Monarda didyma L. extract as a powerful candidate for future geroprotective therapies, with the potential to significantly impact healthy aging.
    Keywords:  Aging people; Biological aging; Botanical extracts; DNA methylation age; Healthy aging; Leukocyte telomere length; Quality of life
    DOI:  https://doi.org/10.1007/s11357-025-01580-2
  26. Geroscience. 2025 Mar 14.
    Topoisomerase inhibitor amonafide enhances defense responses to promote longevity in C. elegans.
    Iman Man Hu, Ana Serna, Stacia Everts, Lale Güngördü, Bauke V Schomakers, Ellen A A Nollen, Arwen W Gao, Riekelt H Houtkooper, Georges E Janssens.
      Aging is a major risk factor for disease, and developing effective pharmaceutical interventions to improve healthspan and promote longevity has become a high priority for society. One of the molecular pathways related to longevity in various model organisms revolves around lowering AKT1 levels. This prompted our in silico drug screen for small molecules capable of mimicking the transcriptional effects of AKT1 knockdown. We found topoisomerase inhibitors as a top candidate longevity-drug class. Evaluating multiple compounds from this class in C. elegans revealed that the topoisomerase inhibitor amonafide has the greatest benefit on healthspan and lifespan. Intriguingly, the longevity effect of amonafide was not solely dependent on DAF-16/FOXO, the canonical pathway for lifespan extension via AKT1 inhibition. We performed RNA-seq on amonafide-treated worms and revealed a more youthful transcriptional signature, including the activation of diverse molecular and cellular defense pathways. We found the mitochondrial unfolded protein response (UPRmt) regulator afts-1 to be crucial for both improved healthspan and extended lifespan upon amonafide treatment. Moreover, healthspan was partially dependent on the immune response transcription factor zip-2 and the integrated stress response transcription factor atf-4. We further examined the potential of amonafide in age-related disease. Treating a C. elegans model for Parkinson's disease with amonafide improved mobility. In conclusion, we identified amonafide as a novel geroprotector, which activates mitochondrial-, pathogen-, and xenobiotic-associated defense responses that-though more studies are needed-may serve as a candidate for Parkinson's disease therapy.
    Keywords:   Caenorhabditis elegans ; Longevity; Topoisomerase inhibitors
    DOI:  https://doi.org/10.1007/s11357-025-01599-5
  27. Eur Geriatr Med. 2025 Mar 13.
    Fndc5/irisin mediates the benefits of aerobic exercise intervention on aging-associated sarcopenia in mice.
    Yuxia Ma, Yi Liu, Jiachuang Zheng, Zhixia Zheng, Jingjing Li.
       METHODS: In this study, 24-month-old (aged) mice were used as a naturally occurring model of aging-associated sarcopenia, while 2-month-old (young) mice served as the normal control. Six weeks of treadmill training was employed as an aerobic exercise intervention. The mRNA and protein levels of fibronectin type III domain-containing protein 5 (Fndc5/irisin), MuRF1, and Atrogin-1 in gastrocnemius muscles were analyzed using qRT-PCR and Western blot. Oxidative stress was assessed using relevant detection kits. Skeletal muscle function was evaluated through the four-paw hanging test, rotarod test, grip strength assay, and measurements of quadriceps, tibialis anterior, and gastrocnemius muscle mass.
    RESULTS: Aerobic exercise interventions enhanced skeletal muscle function by increasing hanging time, maximum speed, grip strength, and increased quadriceps, gastrocnemius, and tibialis anterior muscle mass. On the other hand, aerobic exercise reduced MuRF1 and Atrogin-1 expression in the gastrocnemius muscles of sarcopenia mice, along with lower malondialdehyde levels, and higher superoxide dismutase activity, T-ATPase, and glutathione peroxidase activity. A decline in Fndc5/irisin expression was further detected in the gastrocnemius muscles with aging. In Fndc5-knockout aged mice, aerobic exercise failed to improve skeletal muscle function compared to wild-type aged mice, as evaluated by hanging time, grip strength, maximum speed, and quadriceps, gastrocnemius, and tibialis anterior muscle mass, further validating the involvement of Fndc5 in the improvement of aging-associated sarcopenia.
    CONCLUSION: Aerobic exercise improves aging-associated sarcopenia in mice, with Fndc5/irisin playing a role in this process.
    Keywords:  Aerobic exercise; Age; Fndc5; Irisin; Sarcopenia
    DOI:  https://doi.org/10.1007/s41999-025-01181-4
  28. Biomed Pharmacother. 2025 Mar 11. pii: S0753-3322(25)00169-6. [Epub ahead of print]185 117975
    Streptococcus thermophilus CNCM I-5570 lysate counteracts the aging process in human dermal fibroblast cells by neutralizing harmful free radicals and impacting antioxidant and anti-inflammatory pathways, thus restoring their physiological functions.
    Francesca Rosaria Augello, Francesca Lombardi, Alessia Ciafarone, Serena Altamura, Massimiliano Marazzato, Serena Artone, Benedetta Cinque, Paola Palumbo.
      Previous studies have highlighted the in vitro and in vivo anti-aging potential of Streptococcus thermophilus prompting us to investigate the biomolecular mechanisms underlying its effects. We evaluated the reparative ability of S. thermophilus lysate in a hydrogen peroxide (H2O2)-induced senescence model of human dermal fibroblasts (HDFs). Cell proliferation, cell number, and senescence level were evaluated by IncuCyte® Live Cell Imager system, trypan blue dye exclusion test and β-galactosidase activity, respectively. We analyzed p21, prolyl 4-hydroxylase A1, intracellular collagen I, nuclear factor E2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB) and heme oxygenase-1 expression through western blot. Extracellular levels of collagen I, interleukin-1β, and IL-6 were assessed by ELISA. The oxidative stress markers were assayed using standard methods. The direct antioxidant activity of probiotic was quantified using multiple techniques. The presence of antioxidant genes in probiotic was detected via PCR assay. Probiotic lysate exposure increased the proliferation rate, counteracted the aging by reducing β-galactosidase activity and p21 levels, promoted collagen I synthesis and neutralized oxidative stress by activating Nrf2. The probiotic lysate inhibited the NF-κB pathway with pro-inflammatory marker downregulation. Notably, we revealed that probiotic exhibited strong free radical scavenging ability, iron-chelating properties, and significant ferric reducing power in a concentration-dependent manner. We identified seven genes with antioxidant function in its genome. Our results show that S. thermophilus lysate is efficacious in suppressing the biomolecular events associated with H2O2-induced cellular aging, thus supporting the reparative action of S. thermophilus, helpful in treating skin aging.
    Keywords:  Collagen; Human dermal fibroblasts; Hydrogen peroxide-induced cell senescence; Inflammation; Oxidative stress; S. thermophilus
    DOI:  https://doi.org/10.1016/j.biopha.2025.117975
  29. FASEB J. 2025 Mar 31. 39(6): e70464
    Muscle-specific Keap1 deletion enhances force production but does not prevent inactivity-induced muscle atrophy in mice.
    Edwin R Miranda, Justin L Shahtout, Shinya Watanabe, Norah Milam, Takuya Karasawa, Subhasmita Rout, Donald L Atkinson, William L Holland, Micah J Drummond, Katsuhiko Funai.
      Immobilization-associated muscle atrophy and weakness appear to be driven in part by oxidative stress. Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) is a critical redox rheostat that regulates oxidative stress responses, and its deletion is known to accelerate muscle atrophy and weakness during aging (sarcopenia) or denervation. Conversely, pharmacologic activation of NRF2 extends mouse lifespan and attenuates sarcopenia. Similarly, deletion of Kelch-like ECH-associated Protein 1 (Keap1), a negative regulator of NRF2, enhances exercise capacity. The purpose of this study was to determine whether muscle-specific Keap1 deletion is sufficient to prevent muscle atrophy and weakness in mice following 7 days of hindlimb unloading (HU). To test this hypothesis, control (Ctrl) and tamoxifen-inducible, muscle-specific Keap1 knockout (mKO) mice were subjected to either normal housing (Sham) or HU for 7 days. Activation of NRF2 in muscle was confirmed by increased mRNA of NRF2 targets thioredoxin 1 (Txn1) and NAD(P)H quinone dehydrogenase 1 (NQO1) in mKO mice. Keap1 deletion had an effect to increase force-generating capacity at baseline. However, muscle masses, cross-sectional area, and ex vivo force were not different between mKO and Ctrl HU mice. In addition, muscle 4-hydroxynonenal-modified proteins and protein carbonyls were unaffected by Keap1 deletion. These data suggest that NRF2 activation improves muscle force production during ambulatory conditions but is not sufficient to prevent muscle atrophy or weakness following 7 days of HU.
    Keywords:  NRF2; carbonyl stress; oxidative stress; redox; sarcopenia
    DOI:  https://doi.org/10.1096/fj.202402810R
  30. J Cell Physiol. 2025 Mar;240(3): e70020
    Daytime-Restricted Feeding Alleviates D-Galactose-Induced Aging in Mice and Regulates the AMPK and mTORC1 Activities.
    Tiepeng Li, Ning Huang, Honghan Chen, Yu Yang, Jian Zhang, Weitong Xu, Hui Gong, Chuhui Gong, Ming Yang, Tingting Zhao, Fangfang Wang, Hengyi Xiao.
      Time-restricted feeding (TRF) is a distinct regimen of intermittent fasting advocated for health improving. Although nighttime TRF (NRF) in rodents is analogous to daytime TRF (DRF) in humans and has health benefits, the effects of DRF on rodent's health remain uncertain. The adverse health effects of DRF in rodents are primarily attributed to its implementation-induced temporal shift in the expression of circadian rhythm-related genes. However, studies also demonstrate the health-beneficial effect of restricted feeding itself on metabolic homeostasis, particularly in periphery tissues. Moreover, the direct effects of DRF on aging progression in rodents are underexplored, highlighting a gap in current research. To explore the overall health effects of long-term DRF in rodents, especially its influence on aging progression, we investigated the impact of long-term DRF on mice under a progeric aging condition. Results showed that both 4-h and 8-h DRF regimens exerted positive effects on aging retardation; these effects were manifested as improved physical and memory capacities, enhanced liver and kidney functions, and reduced oxidative damage and inflammatory response. These DRF regimens also lowered the manifestation of aging-related markers in peripheral tissues, with decreased SA-β-gal staining and p16 expression. Mechanistically, DRF regimens, especially DRF8, upregulated AMPK signaling and downregulated mTORC1 signaling. Interestingly, the health benefits of DRF are similar to those of metformin intervention. In conclusion, our study demonstrates for the first time that DRF effectively counteracts oxidative stress-induced aging progression in mice, supporting the viewpoint that TRF as a promising strategy for preventing aging and aging-related disorders.
    Keywords:  AMPK; aging; mTOR; oxidative stress; time‐restricted feeding
    DOI:  https://doi.org/10.1002/jcp.70020
  31. Aging Dis. 2025 Feb 21.
    Beyond pills and prescriptions: Exploring aging-related diseases with non-pharmacological strategies and molecular innovations.
    Mahdi Esmaeilzadeh, Nasrollah Moradikor.
      This paper provides a thorough examination of aging-related diseases, exploring into the intricate molecular mechanisms that underline their development and progression. It explores cutting-edge therapeutic interventions aimed at addressing these conditions, with a particular focus on non-pharmacological approaches such as personalized lifestyle modifications, cognitive enhancement strategies, and robust social engagement initiatives. Additionally, it highlights emerging modalities including gene therapy and precision medicine as promising avenues for mitigating the challenges associated with age-related ailments. Despite significant strides in research, persistent barriers such as limited healthcare access and regulatory complexities continue to impede the widespread implementation of these innovative approaches. Overcoming these obstacles requires collaborative efforts to promote health equity and ensure equitable access to transformative treatments. By advancing our understanding and embracing innovative paradigms, we can catalyze a profound transformation toward healthier aging trajectories. Through sustained interdisciplinary collaborations, rigorous research endeavors, and proactive advocacy initiatives, we can aspire to cultivate a future where aging is synonymous with vitality, dignity, and enhanced well-being for individuals worldwide.
    DOI:  https://doi.org/10.14336/AD.2024.0560
  32. Front Pharmacol. 2025 ;16 1498280
    Anti-aging activities of an ethanolic extract of Lycium ruthenicum in Caenorhabditis elegans based on metabonomic analysis.
    Boya Cui, Lanying Liu, Xinmeng Qiao, Tao Shi, Min Yin, Shu Xu, Xu Feng, Yu Shan.
      The fruits of Lycium ruthenicum Murr. (Solanaceae) are employed in ethnomedicine and used as a functional food. Their antioxidant, anti-aging, and hypolipidemic activities have been investigated in modern research. This study indicated that the ethanolic extract of the fruits of L. ruthenicum Murr. (LRM) improved oxidative and heat stress tolerance, reduced the accumulation of lipofuscin, and retarded the aging process in Caenorhabditis elegans (Rhabditidae). Furthermore, the pharyngeal pumping rate and body length decreased under LRM treatment. Moreover, metabolomic analysis and the DPClusO algorithm revealed that LRM regulated a series of lifespan-related pathways centered on glycine, serine, and threonine metabolism. These results suggest that LRM prolongs the lifespan of Caenorhabditis elegans via dietary restriction. Moreover, feruloyl putrescine, a kind of polyamine, was found in differential metabolites, which may be the metabolite of caffeoyl-spermidine in LRM. These findings from this exploratory study offer a new insight into the roles of L. ruthenicum in anti-aging activity as a functional food.
    Keywords:  dietary restriction; glycine, serine, and threonine metabolism; lifespan; nematode; spermidine
    DOI:  https://doi.org/10.3389/fphar.2025.1498280
  33. Clin Cosmet Investig Dermatol. 2025 ;18 511-523
    Progress in the Application of Molecular Hydrogen in Medical Skin Cosmetology.
    Nan Guo, Yating Zhang.
      Molecular hydrogen is a colorless, tasteless, biologically active small-molecule gas with reducing properties, demonstrating therapeutic and preventive effects across various human systems. Its mechanisms of action include selective antioxidation, anti-inflammatory effects, apoptosis inhibition, and the regulation of gene expression and signaling pathways. In the skin, molecular hydrogen reduces oxidative damage by scavenging free radicals and inhibiting oxidative stress, leading to improvements in texture and tone. It also regulates the inflammatory response, alleviating redness, itching, and discomfort, while promoting skin repair and regeneration. Moreover, hydrogen activates antioxidant enzymes in skin cells, boosting their antioxidant capacity and delaying aging. Clinical trials show that molecular hydrogen significantly improves conditions like acne, chloasma, and skin sensitivity. However, research in skin cosmetology remains in its early stages, with unanswered questions regarding mechanisms of action, optimal dosage, and long-term safety. Further investigation through clinical trials is essential for expanding its applications in this field. Molecular hydrogen holds significant promise in skin cosmetology, and as research and technology evolve, it is expected to drive innovations and breakthroughs in skin care. This review examines the therapeutic potential, mechanisms, and clinical applications of molecular hydrogen in skin cosmetology, addressing challenges and proposing pathways for future advancements in this field.
    Keywords:  hydrogen; hydrogen-rich water; molecular hydrogen; skin beauty
    DOI:  https://doi.org/10.2147/CCID.S500255
  34. Sci Rep. 2025 Mar 10. 15(1): 8260
    Protective effects of Rosa roxburghii Tratt. extract against UVB-induced inflammaging through inhibiting the IL-17 pathway.
    Shuhong Zhang, Yueyue Chen, Liping Qu.
      Chronic inflammation is a critical mechanism contributing to the aging process; however, research specifically addressing chronic inflammation in skin biology remains limited. This study investigates the protective mechanism of Rosa roxburghii Tratt. (RRT) extract against UVB-induced inflammaging. RRT extract effectively reduces the secretion of IL-6, IL-1α, TNF-α, and PGE2 in keratinocytes. Additionally, it attenuates UVB-induced IL-17 pathway activation by downregulating IL-17RA, c-Fos, and c-Jun protein levels, as well as the gene expression of IL-17RA, TRAF6, HSP90, and IKKγ. Co-culturing human foreskin fibroblasts (HFF) with inflammatory factors secreted by UVB-exposed keratinocytes reveals that these factors significantly reduce mitochondrial membrane potential and mitochondrial reactive oxygen species (ROS), thereby promoting aging in HFF. The anti-inflammaging effects of RRT extract are achieved through the reduction of β-galactosidase activity, targeting of the TGF-β1-Smad2/3 signaling pathway, upregulation of COL1A1 expression, and reduction of senescence-associated secretory phenotype secretion. This study provides a novel perspective and robust scientific foundation for exploring mechanisms of skin aging and potential therapeutic interventions.
    Keywords:   Rosa. roxburghii Tratt.; Human foreskin fibroblasts; IL-17 signal pathway; Inflammaging; Inflammatory factors; Keratinocytes
    DOI:  https://doi.org/10.1038/s41598-025-92559-8
  35. FASEB Bioadv. 2025 Mar;7(3): e1491
    Chronic treatment of old mice with AICAR reverses age-related changes in exercise performance and skeletal muscle gene expression.
    Shalene H Wilcox, Jouber Calixto, Steven D Dray, Daniel M Rasch, Andrew H Smith, Kole D Brodowski, Jonathon T Hill, David M Thomson.
      Sarcopenia refers to the decline in muscle mass and function that occurs with advancing age. It is driven by alterations in multiple cellular processes. AMP-activated protein kinase (AMPK) is a cellular energy sensor that opposes many age-related changes, making it an attractive target for the treatment of sarcopenia. This study aimed to test the effect of chronic treatment of old mice with the AMPK-activating prodrug, AICAR, on treadmill running capacity and muscle mass, force production, gene expression, and intracellular markers relevant to sarcopenia. Old (23 months) mice were tested for treadmill running capacity, then randomly assigned to receive daily treatment with AICAR (OA; 300 to 500 mg/kg, delivered via subcutaneous injection) or an equivalent volume of saline vehicle (OS) for 31 days. Young (5 months) saline-treated mice (YS) served as controls. Treadmill posttesting was performed after 24 days, and the mice were euthanized after 31 days of treatment. Extensor digitorum longus (EDL) muscles were tested for force generation and RNA sequencing, RT-PCR, and western blotting were performed on quadricep muscles. Treadmill running capacity declined from pre- to posttesting by 24.5% in OS mice. This decline was not observed in YS or OA mice. Quadricep weight was ~8% higher, and tetanic force production by the EDL muscle increased by 26.4% in OA versus OS. These phenotypic improvements with AICAR treatment were accompanied by changes in gene expression in OA/YS versus OS muscles consistent with the "rejuvenation" of gene ontologies associated with connective tissue, neurodegenerative disease, Akt signaling, and mitochondrial function, among others. AICAR increased the mitochondrial markers cytochrome C by ~33%, and citrate synthase by ~22%. Serum insulin-like growth factor-1 levels increased, and Akt phosphorylation tended (p = 0.07) to increase with AICAR treatment. Although protein levels of the mTORC1 signaling pathway intermediate, rpS6, were higher in OA versus OS muscles, the phosphorylation of mTORC1 pathway intermediates was unaffected. On the other hand, gene expression of the muscle-specific ubiquitin ligases Mafbx and Murf1 were reduced with AICAR treatment. AICAR treatment mildly increased/preserved muscle mass and force production and prevented a decline in treadmill running performance in old mice. These effects were associated with altered skeletal muscle gene and protein expression, suggesting improved mitochondrial content and metabolic signaling (particularly through Akt) as contributing factors to the observed phenotypic effects. Our findings support further development of AMPK-activating drugs as a therapeutic strategy for improving age-related organismal dysfunction and sarcopenia.
    Keywords:  AMPK; exercise; mTORC1; mitochondria; sarcopenia
    DOI:  https://doi.org/10.1096/fba.2024-00252
  36. J Sci Food Agric. 2025 Mar 11.
    Lacticaseibacillus rhamnosus GG improves behavior, immune functions, and biological age markers in female mice with premature aging.
    Estefanía Díaz-Del Cerro, Judith Félix, Beatriz Solo de Zaldívar, M Carmen Martínez-Cuesta, Noemí Ceprián, Teresa Requena, Mónica De la Fuente.
       BACKGROUND: Prematurely aged mice (PAM), characterized by an inadequate stress response, exhibit early immunosenescence and reduced lifespan compared with exceptional non-PAM (E-NPAM) of the same age. Lacticaseibacillus rhamnosus GG (LGG) has been proposed as a beneficial probiotic in healthy aging. This study aimed to evaluate the effects of LGG consumption over 2 and 4 weeks on behavioral parameters, peritoneal leukocyte function, and lifespan in adult female PAM.
    RESULTS: Female ICR-CD1 mice were classified as either PAM or E-NPAM and divided into three groups: (1) PAM control (PAMC), (2) PAM receiving LGG (PAMLGG), and (3) E-NPAM control (E-NPAMC). The PAMLGG group consumed a lyophilized LGG suspension in skim milk for 4 weeks, while the PAMC and E-NPAMC groups received a skim milk solution. Behavioral tests were conducted after 2 weeks, and leukocyte function was analyzed after 2 and 4 weeks. The results showed that the PAMLGG group exhibited improved behavioral responses and enhanced immune functions, which was reflected in a lower biological age and in a longer longevity compared with the PAMC.
    CONCLUSION: LGG supplementation positively influenced behavior, immune function, and biological age markers in female PAM, leading to increased longevity. These findings indicate that LGG administration could be a good nutritional strategy for slowing down the aging process, allowing a healthy longevity to be achieved. © 2025 Society of Chemical Industry.
    Keywords:  Lacticaseibacillus rhamnosus GG; aging; behavior; biological age; immune functions; longevity
    DOI:  https://doi.org/10.1002/jsfa.14219
  37. Ageing Res Rev. 2025 Mar 08. pii: S1568-1637(25)00071-6. [Epub ahead of print]107 102725
    Cognition on the move: Examining the role of physical exercise and neurogenesis in counteracting cognitive aging.
    Sahand Farmand, Andrea Du Preez, Curie Kim, Chiara de Lucia, Marc-David Ruepp, Brendon Stubbs, Sandrine Thuret.
      Structural and functional aspects of the hippocampus have been shown to be sensitive to the aging process, resulting in deficits in hippocampal-dependent cognition. Similarly, adult hippocampal neurogenesis (AHN), described as the generation of new neurons from neural stem cells in the hippocampus, has shown to be negatively affected by aging throughout life. Extensive research has highlighted the role of physical exercise (PE) in positively regulating hippocampal-dependent cognition and AHN. Here, by critically reviewing preclinical and clinical studies, we discuss the significance of PE in reversing age-associated changes of the hippocampus via modulation of AHN. We indicate that PE-induced changes operate on two main levels. On the first level, PE can potentially cause structural modifications of the hippocampus, and on the second level, it regulates the molecular and cellular pathways involved. These changes result in the vascular remodelling of the neurogenic niche, as well as the secretion of neurotrophic and antioxidant factors, which can in turn activate quiescent neural stem cells, while restoring their proliferation capacity and boosting their survival - features which are negatively impacted during aging. Understanding these mechanisms will allow us to identify new targets to tackle cognitive aging and improve quality of life.
    Keywords:  Adult hippocampal neurogenesis; Aging; Cognition; Physical exercise; The hippocampus
    DOI:  https://doi.org/10.1016/j.arr.2025.102725
  38. Foods. 2025 Feb 21. pii: 737. [Epub ahead of print]14(5):
    Characterization and Anti-Aging Potency of Phenolic Compounds in Xianhu Tea Extracts.
    Guangwen Zhang, Wenwen Jiang, Qing Hu, Jianming Luo, Xichun Peng.
      The health benefits of tea are primarily attributed to its chemical composition, particularly phenolic compounds. As a renowned tea from Guangdong, China, Xianhu tea (XHT) has not been thoroughly studied in terms of its phenolic composition or health-promoting properties. This study characterized the phenolic compounds in Xianhu tea water extract (XHT) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and evaluated its antioxidant activity in vitro. Furthermore, the effects of XHT extracts on reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), lipofuscin levels, and lifespan in Caenorhabditis elegans were assessed, alongside their modulation of aging-related genes. Compared with Xinyang Maojian tea water extract (XYMJ) and Yingde black tea water extract (YDBT), XHT exhibited a significantly higher polyphenol content, with 23 phenolic compounds identified as characteristic markers. XHT demonstrated superior 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) inhibition capacities, the greatest reductions in ROS, MDA, and lipofuscin levels, and the highest upregulation of SOD and CAT activities. The lifespan was 23.50% and 21.07% significantly longer than nematodes in the control group. Moreover, XHT modulated 13 aging-related genes, which strongly correlated with the 23 identified phenolic compounds. The research results of the above indicators were all obtained without affecting the normal feeding and reproductive capabilities of C. elegans. These findings suggest that these phenolics are the key bioactive components responsible for the anti-aging effects of XHT.
    Keywords:  C. elegans; anti-aging; antioxidation; phenols
    DOI:  https://doi.org/10.3390/foods14050737
  39. Aging Cell. 2025 Mar 10. e70033
    Associations Between Leisure-Time Physical Activity and Metabolomics-Based Markers of Biological Aging in Late Midlife: Short-Term and Long-Term Follow-Up.
    Katri Ruutu, Niko S Wasenius, Kothandaraman Narasimhan, Tuija M Mikkola, Merja K Laine, Johan G Eriksson.
      Physical activity (PA) may delay the onset of age-related diseases by decelerating biological aging. We investigated the association between leisure-time physical activity (LTPA) and metabolomics-based aging markers (MetaboAge and MetaboHealth) in late midlife and during 16 years of follow-up. At the 16-year follow-up, we also investigated the association between device-based PA and MetaboAge and MetaboHealth. We included 1816 individuals (mean age 61.6 years) from the Helsinki Birth Cohort Study at baseline and followed them up for 5 (n = 982) and 16 years (n = 744), respectively. LTPA was assessed via questionnaire at baseline and 16 years later and device-based PA with ActiGraph accelerometer at the 16-year follow-up. Fasting blood samples were applied to calculate MetaboAge acceleration (ΔmetaboAge) and MetaboHealth at baseline and at both follow-ups. Covariate-adjusted multiple regression analyses and linear mixed models were applied to study the associations. A higher volume of LTPA at baseline was associated with a lower MetaboHealth score at the 5-year follow-up (p < 0.0001 for time × LTPA interaction). No associations were detected at the 16-year follow-up. An increase in LTPA over 16 years was associated with a decrease in MetaboHealth score (p < 0.001) and a decrease in LTPA with an increase in MetaboHealth score. Higher device-based PA was associated with a lower MetaboHealth score, but not with ΔmetaboAge. In conclusion, higher LTPA in late midlife and device-based PA in old age were associated with improved MetaboHealth. Increasing LTPA with age may protect against MetaboHealth-based aging. The results support the importance of PA for biological aging in later life.
    Keywords:  accelerometer‐based physical activity; biological aging; leisure‐time physical activity; metabolic aging; metabolomics
    DOI:  https://doi.org/10.1111/acel.70033
  40. Geroscience. 2025 Mar 12.
    Long-term dietary allyl isothiocyanate, a TRPA1 agonist, ameliorates cardiac fibrosis and diastolic dysfunction in aged mice.
    Chunqi Qian, Zachary Fernandez, Seyed A Sadeghi, Arman Fotouhi, Liangliang Sun, Donna H Wang, Shuangtao Ma.
      Transient receptor potential ankyrin 1 (TRPA1) is a sensory channel expressed in vagal afferent nerves that detect noxious stimuli. Trpa1 knockout accelerates age-related cardiac fibrosis and dysfunction in mice. This study investigated whether TRPA1 activation with its selective agonist, allyl isothiocyanate (AITC), prevents cardiac aging. Male and female 18-month-old C57BL/6 J mice were randomized to receive either a control diet or a diet containing 15 mg of AITC per kilogram of food for 6 months. At 24 months, aged mice on the control diet exhibited increased left ventricular wall thickness but maintained similar left ventricular volume and preserved systolic function compared to 18-month-old middle-aged mice. Additionally, aged mice on a control diet developed restrictive-like cardiomyopathy, characterized by a pathologically elevated E/A ratio. AITC treatment significantly improved diastolic function by normalizing the E/A ratio (P < 0.01) and shortening isovolumetric relaxation time (P < 0.01), without affecting left ventricular wall thickness, volume, or systolic function. Electrocardiographic analysis demonstrated that AITC treatment significantly increased heart rate variability (P < 0.01) and parasympathetic nervous system index (P < 0.05), indicating enhanced vagal activity. Histological analyses revealed decreased cardiac fibrosis and collagen I/III deposition in AITC-treated mice (all P < 0.01). Proteomics analysis demonstrated that differentially expressed proteins in myocardial tissue were mainly enriched in pathways of collagen metabolism, extracellular matrix-receptor interaction, and fatty acid metabolism. These findings suggest that long-term dietary AITC may improve vagal tone, reduce cardiac fibrosis, and enhance diastolic function in aged mice, potentially through TRPA1 activation. TRPA1 could be a promising therapeutic target for age-related diastolic dysfunction.
    Keywords:  Allyl isothiocyanate; Cardiac aging; Diastolic dysfunction; HFpEF; TRPA1
    DOI:  https://doi.org/10.1007/s11357-025-01603-y
  41. Arch Dermatol Res. 2025 Mar 09. 317(1): 542
    Mushrooms in modern cosmetics: unlocking anti-aging, antioxidant, and therapeutic potential.
    Saliha Rukhsar, Muhammad Usman, Nousheen Yousaf, Ghulam Murtaza, Muhammad Aamir Manzoor, Muhammad Azam.
      Mushrooms have gained significant attention in the cosmetics industry due to their rich bioactive compounds with numerous skin benefits. This review explores the potential of various mushroom species as ingredients in cosmeceuticals, focusing on their anti-aging, anti-wrinkle, skin whitening, moisturizing, antioxidant, anti-inflammatory, and antimicrobial properties. Mushrooms such as Ganoderma lucidum, Lentinula edodes, Pleurotus ostreatus, and Agaricus bisporus have demonstrated the ability to inhibit key enzymes like elastase, tyrosinase, hyaluronidase, and collagenase, which play vital roles in skin aging and pigmentation. These bioactive compounds, including polysaccharides, phenolic acids, vitamins, and carotenoids, contribute to reduce wrinkles, improving skin hydration, enhancing elasticity, and providing protection from oxidative stress and UV damage. Furthermore, mushrooms have shown antimicrobial activities, making them effective against skin infections and inflammation. Mushrooms have become a popular ingredient in hair care products for their nourishing benefits, helping to promote healthy hair growth and protect against damage. As demand for natural, sustainable, and effective skincare alternatives rises, the incorporation of mushrooms into cosmetic formulations offers a promising solution. This review highlights the growing application of mushrooms in the development of innovative cosmeceuticals and emphasizes the need for further research to explore their full potential. Advancements in extraction techniques and the identification of new bioactive compounds are expected to enhance the efficacy of mushroom-based skincare products, making them an integral part of the global cosmetics market in the future.
    Keywords:  Anti-aging; Antioxidant activity; Mashrooms
    DOI:  https://doi.org/10.1007/s00403-025-04048-7
  42. Int J Mol Sci. 2025 Mar 06. pii: 2354. [Epub ahead of print]26(5):
    Effectiveness of Extracellular Vesicle Application in Skin Aging Treatment and Regeneration: Do We Have Enough Evidence from Clinical Trials?
    Anna Domaszewska-Szostek, Marta Krzyżanowska, Agnieszka Polak, Monika Puzianowska-Kuźnicka.
      In recent years, there has been a dynamic development in therapies utilizing extracellular vesicles (EVs) including exosomes. Therefore, we have conducted an analysis of the scientific literature to verify the current state of knowledge about these therapies. A total of 12 clinical studies were analyzed, covering the use of EVs in treating skin aging, acne scars, alopecia, and wound healing. The results indicate that EVs and exosomes hold potential in regenerative skin therapies, offering innovative and non-invasive therapeutic approaches. At the same time, significant challenges related to the standardization of their production and the lack of large-scale randomized studies were identified. Thus, we also evaluated the investigated clinical trials in regard to the MISEV (Minimal Information for Studies of Extracellular Vesicles) criteria. This review provides a comprehensive overview of the contemporary applications of EVs in skin therapy and regenerative medicine, highlighting directions for further research.
    Keywords:  clinical trials; exosomes; extracellular vesicles; regenerative medicine; skin aging
    DOI:  https://doi.org/10.3390/ijms26052354
  43. Sci Rep. 2025 Mar 12. 15(1): 8587
    Elevated urinary phytoestrogens are associated with delayed biological aging: a cross-sectional analysis of NHANES data.
    Jing Wang, Qiancheng Cao, Minjie Gao, Yiru Pan, Yanan Chen, Yifei Cao, Shufen Han, Xiao Yan, Xianrong Xu, Xuexian Fang, Fuzhi Lian.
      Dietary phytoestrogens have been suggested to provide protection against numerous age-related diseases. However, their effects on biological aging remain unclear. In this study, we cross-sectionally investigated the relationship between urinary phytoestrogen levels and indicators of biological aging using data from 7,981 adults who participated in the National Health and Nutrition Examination Survey 1999-2010. Urinary concentrations of six phytoestrogens, including four isoflavones and two enterolignans, were measured using high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS) or HPLC-atmospheric pressure photoionization-tandem MS, and standardized using urinary creatinine. Three indicators of biological age (BA), namely the Klemera-Doubal method biological age (KDM-BA), phenotypic age (PA), and homeostatic dysregulation (HD), were derived from 12 clinical biomarkers, advanced-BAs were calculated to quantify the differences between individuals' BAs and chronological age, and individuals with all positive advanced-BAs were defined as accelerated-aging. Weighted linear regression analysis showed that after adjusting for demographic and lifestyle factors and history of chronic diseases, elevated urinary total phytoestrogen and enterolignans were significantly associated with less advanced-KDM, advanced-PA, and advanced-HD, whereas elevated urinary isoflavones was significantly associated with less advanced-KDM and advanced-PA but not with advanced-HD. Weighted logistic regression showed that higher urinary levels of total phytoestrogen (highest Q4 vs. lowest Q1: OR = 0.60, 95%CI: 0.44, 0.80; P-trend = 0.002) and enterolignans (Q4 vs. Q1: OR = 0.59, 95%CI: 0.45, 0.76; P-trend < 0.001) were significantly associated with lower odds of accelerated-aging, but this was not significant for isoflavones (Q4 vs. Q1: OR = 0.78, 95%CI: 0.60, 1.08; P-trend = 0.05). Subgroup analyses showed that negative associations were attenuated in non-overweight/obese participants and current cigarette smokers. In conclusion, higher levels of urinary phytoestrogens are related to markers of slower biological aging, suggesting an anti-aging effect of higher dietary phytoestrogen consumption, which warrants further investigations in longitudinal or interventional settings.
    Keywords:  Biological aging; Enterolignans; Isoflavones; NHANES; Phytoestrogen
    DOI:  https://doi.org/10.1038/s41598-025-88872-x
  44. Phytomedicine. 2025 Mar 12. pii: S0944-7113(25)00232-6. [Epub ahead of print]140 156592
    Mixtures of EGCG, bamboo leaf flavonoids, and broccoli seed water extracts exhibit anti-glycation and skin-protective effects.
    Chang Sun, Zibin Liu, Mengmeng Feng, Junbo Wang, Yanfei Jiang, Chunyue Zhao.
       BACKGROUND: Skin aging is a multifaceted process. Glycation significantly contributes to skin aging and the development of complications. Researchers are currently investigating various substances, particularly those from natural sources, to combat skin glycation.
    PURPOSE: This study aimed to comprehensively evaluate the anti-glycation effect of a new natural combination, EBB, which includes (-)-epigallocatechin-3 gallate (EGCG), bamboo leaf flavonoids, and broccoli seed water extracts, using cell and animal models and to explore its potential anti-glycation mechanism.
    METHODS: The components of EBB were identified using HPLC and UHPLC-MS/MS. Additionally, a glycation cell model induced by glyceraldehyde, advanced glycation end products (AGEs), and methylglyoxal was established in HaCaT cells to evaluate the efficacy of EBB in alleviating glycation. Differential genes, signalling pathways, and biological processes were analysed through RNA sequencing to explore the mechanisms of the anti-glycation effects of EBB, which were further validated using qRT-PCR and Western blotting. Finally, the protective effects of EBB against glycation and skin damage were assessed in zebrafish and mouse in vivo models through histological studies and the measurement of various skin physiological parameters.
    RESULTS: Glucoraphanin, Sinapine and orientin were identified in EBB, which effectively reduced the formation of AGEs and decreased the expression level of the RAGE protein in HaCaT cells. Transcriptomic analyses revealed that EBB regulated the expression of 576 differentially expressed genes. These genes were enriched in various biological processes, such as chronic inflammation and immune responses, and participated in the regulation of multiple signalling pathways, including TNF. Glycation upregulated the expression of the ROS1 gene and protein, while EBB reversed this effect. Furthermore, EBB attenuated the glycation response by downregulating the expression levels of proteins such as p-p38, p-ERK1/2, p-p65, and TNF-α. Additionally, the reduction of AGE accumulation by EBB was confirmed in a zebrafish model. Similarly, histological analyses of mouse skin tissue and various physiological parameters demonstrated that EBB significantly mitigated damage induced by glycation.
    CONCLUSIONS: Our results show that EBB effectively inhibited glycation reactions. The mechanism of action may involve the reduction of inflammation by downregulating the expression levels of RAGE and ROS1, thereby decreasing the accumulation of AGEs in keratinocytes and alleviating skin damage. This paves the way for the potential application of EBB as a valuable anti-glycation functional ingredient in the food and cosmetic industries.
    Keywords:  Bamboo leaf flavonoids; Broccoli seed water extracts; EGCG; Glycation; Skin ageing
    DOI:  https://doi.org/10.1016/j.phymed.2025.156592
  45. Int J Mol Sci. 2025 Feb 23. pii: 1915. [Epub ahead of print]26(5):
    Influence of Klotho Protein Levels in Obesity and Sarcopenia: A Systematic Review.
    Diana G Ariadel-Cobo, Brisamar Estébanez, Elena González-Arnáiz, María Pilar García-Pérez, Marta Rivera-Viloria, Begoña Pintor de la Maza, David Emilio Barajas-Galindo, Diana García-Sastre, María D Ballesteros-Pomar, María J Cuevas.
      The Klotho gene is recognized for its anti-aging properties. Its downregulation leads to aging-like phenotypes, whereas overexpression can extend lifespan. Klotho protein exists in three forms: α-klotho, β-klotho and γ-klotho. The α-klotho has two isoforms: a membrane-bound form, primarily in the kidney and brain, and a secreted klotho protein present in blood, urine, and cerebrospinal fluid. Klotho functions as a co-receptor for fibroblast growth factor-23 (FGF23), regulating phosphate metabolism. The membrane-bound form controls various ion channels and receptors, while the secreted form regulates endocrine FGFs, including FGF19 and FGF21. The interaction between β-klotho and FGF21 in muscle is critical in the development of sarcopenic obesity. This systematic review, registered in PROSPERO and conducted following PRISMA guidelines, evaluates klotho levels in individuals with obesity or sarcopenic obesity. The study includes overweight, obese, and sarcopenic obese adults compared to those with a normal body mass index. After reviewing 713 articles, 20 studies were selected, including observational, cross-sectional, cohort studies, and clinical trials. Significant associations between klotho levels and obesity, metabolic syndrome (MS), and cardiovascular risk were observed. Exercise and dietary interventions positively influenced klotho levels, which were linked to improved muscle strength and slower decline. Klotho is a potential biomarker for obesity, MS, and sarcopenic obesity. Further research is needed to explore its mechanisms and therapeutic potential.
    Keywords:  FGF; Klotho; adipose tissue; inflammaging; sarcopenic obesity
    DOI:  https://doi.org/10.3390/ijms26051915
  46. Int J Mol Sci. 2025 Mar 06. pii: 2369. [Epub ahead of print]26(5):
    Development of a PLA Polymer-Based Liquid Filler for Next-Generation Aesthetics.
    Ji Hyun Sung, Na Jeong Park, Jeong Eun Park, Hye Sung Yoon, Ji Hyeon Baek, Helen Cho, Ji Hoon Park.
      In regard to both natural aging and photoaging caused by UV radiation, a decrease in skin collagen and elastin fibers results in the loss of soft tissue volume. Biodegradable polymer fillers have been used to overcome this problem, but the slow rate of reconstruction and particle agglomeration has limited this approach. The DMSB01 filler, which consists of poly d-l-lactic acid (PDLLA) with a methoxy polyethylene glycol (mPEG) initiator, was created to address this issue. In this study, we assessed the reconstruction and dispersion of the DMSB01 filler in vitro, as well as its effect on collagen expression in rats. DMSB01 showed rapid reconstruction and excellent dispersion stability; gelation occurred within 5 min at 37 °C and remained stable. In an animal model, DMSB01 induced M2 macrophages, Transforming growth factor beta (TGF-β) expression, and significantly increased collagens I and III. Collagen recovery and wrinkle improvement were confirmed by the aging and photoaging models, and hematoxylin and eosin (H&E) staining was used to demonstrate the safety and biodegradability of DMSB01. DMSB01 was effective in terms of inducing collagen production and improving skin aging, and shows promise as an innovative ingredient to overcome the limitations of existing fillers.
    Keywords:  PLA filler; biodegradable polymer; collagen stimulator; dermal filler; phagocytosis; skin rejuvenation
    DOI:  https://doi.org/10.3390/ijms26052369
  47. Rejuvenation Res. 2025 Mar 11.
    Continuing the Legacy: Understanding and Reducing Tissue Aging to Prevent Many Currently Incurable Diseases.
    Irina Conboy.
      
    DOI:  https://doi.org/10.1089/rej.2025.0012
  48. Molecules. 2025 Mar 06. pii: 1178. [Epub ahead of print]30(5):
    Polysaccharides with Arabinose: Key Players in Reducing Chronic Inflammation and Enhancing Immune Health in Aging.
    Patricia Pantoja Newman, Brenda Landvoigt Schmitt, Rafael Moura Maurmann, Brandt D Pence.
      Aging is associated with a decline in physiological performance leading to increased inflammation and impaired immune function. Polysaccharides (PLs) found in plants, fruits, and fungi are emerging as potential targets for therapeutic intervention, but little is known about their effects on chronic inflammation and aging. This review aims to highlight the current advances related to the use of PLs, with the presence of arabinose, to attenuate oxidative stress and chronic and acute inflammation, and their immunomodulatory effects associated with antioxidant status in monocytes, macrophages, and neutrophil infiltration, and leukocyte rolling adhesion in neutrophils. In addition, recent studies have shown the importance of investigating the 'major' monosaccharide, such as arabinose, present in several of these polysaccharides, and with described effects on gut microbiome, glucose, inflammation, allergy, cancer cell proliferation, neuromodulation, and metabolic stress. Perspectives and opportunities for further investigation are provided. By promoting a balanced immune response and reducing inflammation, PLs with arabinose or even arabinose per se may alleviate the immune dysregulation and inflammation seen in the elderly, therefore providing a promising strategy to mitigate a variety of diseases.
    Keywords:  arabinose; inflammaging; innate immune system; polysaccharide
    DOI:  https://doi.org/10.3390/molecules30051178
  49. J Ethnopharmacol. 2025 Mar 08. pii: S0378-8741(25)00277-6. [Epub ahead of print]345 119593
    Exploring the mechanisms of cow placental peptides in delaying liver aging based on mitochondrial energy metabolism.
    Zeru Zhang, Yuxin Luo, Hanwen Zhang, Zhi Zeng, Weijian Zheng, Yuquan Zhao, Yixin Huang, Liuhong Shen.
       ETHNOPHARMACOLOGICAL RELEVANCE: Placenta is a kind of traditional Chinese medicine, known as "Ziheche". The role of cow placental peptides (CPP) in delaying liver aging has been reported, and in-depth exploration of the specific regulatory mechanisms is of great significance for the recycling and utilization of CPP and the development of natural anti-aging drugs.
    AIM OF THE STUDY: To investigate the protective effects and mechanisms of CPP on liver aging induced by D-galactose (D-gal) in mice from the perspective of mitochondrial energy metabolism.
    METHODS: An aging model was induced in mice using D-gal. The body weight and liver index of mice were measured, followed by staining and electron microscopy to observe liver morphology and aging markers. Reactive oxygen species (ROS) levels and antioxidant-related indicators were assessed, and mitochondrial function was evaluated. Finally, changes and mechanisms in liver transcriptomics and targeted mitochondrial energy metabolomics were analyzed and integrated to elucidate the regulatory pathways through which CPP delays liver aging.
    RESULTS: CPP improved liver structural damage, oxidative stress, and mitochondrial dysfunction induced by D-galactose in aging mice. It increased the final body weight and liver index, alleviated hepatocyte swelling and degeneration, enhanced liver antioxidant capacity, and restored normal mitochondrial morphology and function. The combined analysis of targeted mitochondrial energy metabolomics and liver transcriptomics revealed that CPP directly or indirectly regulated mitochondrial energy metabolism and delayed aging by influencing the cAMP signaling pathway, PI3K-Akt signaling pathway, oxidative phosphorylation, and other pathways, thereby modulating related genes and metabolites.
    Keywords:  Aging; Cow placental peptides; Liver; Mitochondrial energy metabolism
    DOI:  https://doi.org/10.1016/j.jep.2025.119593
  50. J Clin Aesthet Dermatol. 2025 Feb;18(2): 44-49
    Reversing Glycation with a Dietary Supplement Containing Rosemary Extract.
    Zoe Draelos, Vivian Bucay, Jacqueline Watchmaker, Giuseppe Valacchi.
       Objective: The authors sought to explore the skin deglycation ability of rosemary extract dietary supplements to support skin health and improve the signs of skin aging.
    Methods: A PubMed literature search for English-language articles on rosemary extract effects on glycation and skin aging in clinical and/or preclinical settings was conducted.
    Results: Endogenous and exogenous glycative stress and reactive oxygen species lead to the accumulation of advanced glycation endproducts (AGEs), accelerating skin aging. Rosemary extract, and its active polyphenol, rosmarinic acid (RA), exhibit antiglycative and antioxidant effects, preventing AGE formation. Rosemary reduces reactive intermediates in the glycation pathway, decreases protein carbonylation, and protects against environmental stressors. Rosemary has shown potential in reversing glycation, benefiting skin health by protecting collagen and elastin. Both topical and oral delivery methods have been investigated and have shown to be beneficial. Manufacturing and extraction methods are critical in preserving essential and synergistic components of the extract when optimizing formulation development.
    Limitations: As a narrative review, the selection of the literature was not fully comprehensive, thus introducing a potential for bias. However, our aim was to provide insights into the impacts of glycation and RA on skin quality and health.
    Conclusion: Rosemary extract and RA appear to exhibit antiglycative effects, both interrupting AGE formation and AGE-protein crosslinks, making them promising compounds for skin health. However, further research is needed to fully understand their mechanisms and therapeutic potential.
    Keywords:  Glycative stress; advanced glycation endproducts (AGEs); antiglycative effects; antioxidant properties; nutraceuticals; rosemary extract; rosmarinic acid; skin aging; skin health
  51. Sci Adv. 2025 Mar 14. 11(11): eadr3757
    Genetically supported targets and drug repurposing for brain aging: A systematic study in the UK Biobank.
    Fan Yi, Jing Yuan, Judith Somekh, Mor Peleg, Yi-Cheng Zhu, Zhilong Jia, Fei Wu, Zhengxing Huang.
      Brain age gap (BAG), the deviation between estimated brain age and chronological age, is a promising marker of brain health. However, the genetic architecture and reliable targets for brain aging remains poorly understood. In this study, we estimate magnetic resonance imaging (MRI)-based brain age using deep learning models trained on the UK Biobank and validated with three external datasets. A genome-wide association study for BAG identified two unreported loci and seven previously reported loci. By integrating Mendelian Randomization (MR) and colocalization analysis on eQTL and pQTL data, we prioritized seven genetically supported druggable genes, including MAPT, TNFSF12, GZMB, SIRPB1, GNLY, NMB, and C1RL, as promising targets for brain aging. We rediscovered 13 potential drugs with evidence from clinical trials of aging and prioritized several drugs with strong genetic support. Our study provides insights into the genetic basis of brain aging, potentially facilitating drug development for brain aging to extend the health span.
    DOI:  https://doi.org/10.1126/sciadv.adr3757
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