bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2025–04–20
thirty-six papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño



  1. Int J Mol Sci. 2025 Apr 04. pii: 3381. [Epub ahead of print]26(7):
      The global rise in aging populations has made healthy longevity a critical priority in medical research. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG), the primary bioactive component of Polygonum multiflorum Thunb. (commonly known as Fallopia multiflora Thunb., He shou wu, Fo-ti, or Polygoni multiflori radix), has emerged as a promising agent for combating aging and age-related diseases. This systematic review evaluates the anti-aging properties of TSG and its protective effects against age-related pathologies. The current evidence demonstrates that TSG exhibits comprehensive anti-aging effects, including lifespan extension, neuroprotection (e.g., ameliorating Alzheimer's and Parkinson's diseases), cardiovascular protection (e.g., reducing atherosclerosis and hypertension), delay of gonadal aging, reduction in bone loss (e.g., mitigating osteoporosis), and promotion of hair regrowth. Mechanistically, TSG alleviates oxidative stress, inflammation, and apoptosis while enhancing mitophagy, mitochondrial function telomerase activity, and epigenetic regulation. These multi-target actions align with the holistic principles of traditional Chinese medicine, highlighting TSG's potential as a multifaceted anti-aging agent. However, further research is required to establish standardized quantitative systems for evaluating TSG's efficacy, paving the way for its broader clinical application in promoting healthy aging.
    Keywords:  2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG); Polygonum multiflorum; age-related diseases; aging; healthy longevity
    DOI:  https://doi.org/10.3390/ijms26073381
  2. Antioxidants (Basel). 2025 Mar 07. pii: 322. [Epub ahead of print]14(3):
      The aging population is steadily increasing, with aging and age-related diseases serving as major risk factors for morbidity, mortality, and economic burden. Peanuts, known as the "longevity nut" in China, have been shown to offer various health benefits, with peanut skin extract (PSE) emerging as a key compound of interest. This study investigates the bioactive compound in PSE with anti-aging potential and explores its underlying mechanisms of action. Procyanidin A1 (PC A1) was isolated from PSE, guided by the K6001 yeast replicative lifespan model. PC A1 prolonged the replicative lifespan of yeast and the yeast-like chronological lifespan of PC12 cells. To further confirm its anti-aging effect, cellular senescence, a hallmark of aging, was assessed. In senescent cells induced by etoposide (Etop), PC A1 alleviated senescence by reducing ROS levels, decreasing the percentage of senescent cells, and restoring proliferative capacity. Transcriptomics analysis revealed that PC A1 induced apoptosis, reduced senescence-associated secretory phenotype (SASP) factors, and modulated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. The antioxidative capacity of PC A1 was also evaluated, showing enhanced resistance to oxidative stress in PC12 cells by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) activity. Moreover, PC A1 induced autophagy, as evidenced by an increase in fluorescence-labeled autophagic compartments and confirmation via Western blot analysis of autophagy-related proteins. In addition, the treatment of an autophagy inhibitor abolished the antioxidative stress and senescence-alleviating effects of PC A1. These findings reveal that PC A1 extended lifespans and alleviated cellular senescence by enhancing oxidative stress resistance and inducing autophagy, positioning it as a promising candidate for further exploration as a geroprotective agent.
    Keywords:  PI3K/Akt signaling pathway; aging; antioxidative stress; autophagy; cell senescence; peanut skin; procyanidin A1
    DOI:  https://doi.org/10.3390/antiox14030322
  3. Life Med. 2025 Apr;4(2): lnaf003
      Cellular senescence is a key contributor to aging and aging-related diseases, but its metabolic profiles are not well understood. Here, we performed a systematic analysis of the metabolic features of four types of cellular senescence (replication, irradiation, reactive oxygen species [ROS], and oncogene) in 12 cell lines using genome-wide metabolic modeling and meta-analysis. We discovered that replicative and ROS-induced senescence share a common metabolic signature, marked by decreased lipid metabolism and downregulated mevalonate pathway, while irradiation and oncogene-induced senescence exhibit more heterogeneity and divergence. Our genome-wide knockout simulations showed that enhancing the mevalonate pathway, by administrating mevalonate for instance, could reverse the metabolic alterations associated with senescence and human tissue aging, suggesting a potential anti-aging or lifespan-extending effect. Indeed, the experiment in Caenorhabditis elegans showed that administrating mevalonate significantly increased the lifespan. Our study provides a new insight into the metabolic landscape of cell senescence and identifies potential targets for anti-aging interventions.
    Keywords:  cellular senescence; meta-analysis; metabolic modeling; metabolic profile
    DOI:  https://doi.org/10.1093/lifemedi/lnaf003
  4. Antioxidants (Basel). 2025 Feb 27. pii: 285. [Epub ahead of print]14(3):
      Coffee is more than a universally loved beverage; it is a complex matrix of bioactive compounds that contribute to its multifaceted health benefits. From its role as a potent source of antioxidants to its potential anti-aging effects, coffee has proven to be a valuable component of a balanced diet. This paper highlights the extensive scientific evidence supporting coffee's ability to combat oxidative stress, enhance cognitive function, and improve metabolic and cardiovascular health. Additionally, its role in modulating key cellular pathways underscores its potential to positively influence aging and longevity. This manuscript emphasizes coffee's broader cultural, economic, and historical significance, illustrating its enduring relevance in contemporary society. Despite minor discrepancies in research findings, the preponderance of evidence underscores coffee's potential as a functional food with profound implications for healthspan and aging. While promising, translating findings to humans requires further clinical research.
    Keywords:  anti-aging; antioxidants; coffee; polyphenols
    DOI:  https://doi.org/10.3390/antiox14030285
  5. Chem Biodivers. 2025 Apr 14. e202500604
      The traditional Chinese herbal medicine Panax ginseng can optimize physical health and is anticipated to be a valuable resource for investigating anti-aging therapies. This study investigated the anti-aging effects of red ginseng aqueous extract (RG) and white ginseng aqueous extract (WG). Network pharmacology forecasted that the key mechanisms of anti-aging in white and red ginseng were the PI3K-Akt and IIS signaling pathways. Experiments conducted on Caenorhabditis elegans (C. elegans) showed that 5 mg/mL WG and RG notably prolonged lifespan and improved stress resistance. The qPCR analysis revealed that changes in upstream genes activated downstream genes in the IIS pathway. Furthermore, forward and reverse validation indicated that WG and RG acted through the IIS pathway in promoting longevity. RG exhibited superior anti-aging effects compared to WG at the same concentration. This might be attributed to the fact that RG contained more reducing sugars, polyphenols, melanoidins, total saponin content and especially the conversion of ginsenosides. Molecular docking showed that ginsenosides interacted with the key protein DAF-2, with ginsenosides Rg3, Rg5, Rh4, Rf, and Rc binding more strongly than ginsenosides Rb1, Rb2, and Rd. Overall, RG possessed different active ingredients compared to WG and showed superior results in improving aging in C. elegans.
    Keywords:  Anti-aging; Caenorhabditis elegans; Oxidative stress; Panax ginseng
    DOI:  https://doi.org/10.1002/cbdv.202500604
  6. Front Aging. 2025 ;6 1541127
      Driven by genetic and environmental factors, aging is a physiological process responsible for age-related degenerative changes in the body, cognitive decline, and impaired overall wellbeing. Notably, premature aging as well as the emergence of progeroid syndromes have posed concerns regarding chronic health conditions and comorbidities in the aging population. Accelerated telomere attrition is also implicated in metabolic dysfunction and the development of metabolic disorders. Impaired metabolic homeostasis arises secondary to age-related increases in the synthesis of free radicals, decreased oxidative capacity, impaired antioxidant defense, and disrupted energy metabolism. In particular, several cellular and molecular mechanisms of aging have been identified to decipher the influence of premature aging on metabolic diseases. These include defective DNA repair, telomere attrition, epigenetic alterations, and dysregulation of nutrient-sensing pathways. The role of telomere attrition premature aging in the pathogenesis of metabolic diseases has been largely attributed to pro-inflammatory states that promote telomere shortening, genetic mutations in the telomerase reverse transcriptase, epigenetic alteration, oxidative stress, and mitochondrial dysfunctions. Nonetheless, the therapeutic interventions focus on restoring the length of telomeres and may include treatment approaches to restore telomerase enzyme activity, promote alternative lengthening of telomeres, counter oxidative stress, and decrease the concentration of pro-inflammatory cytokines. Given the significance and robust potential of delaying telomere attrition in age-related metabolic diseases, this review aimed to explore the molecular and cellular mechanisms of aging underlying premature telomere attrition and metabolic diseases, assimilating evidence from both human and animal studies.
    Keywords:  aging; metabolic diseases; premature aging; telomerase; telomere
    DOI:  https://doi.org/10.3389/fragi.2025.1541127
  7. Curr Res Microb Sci. 2025 ;8 100381
      Old age raises the susceptibility of age-related disease in domestic dogs. Discovering effective anti-aging interventions is key for mitigating age-related disease and conserving "healthspan" in pet dogs. In this study, 2 bacterial strains were isolated from canine feces. After screening and identifying the strains, Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 were chosen to intervene during d-galactose-induced senescence in mice. We found that administering Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 improved the aging phenotype of mice, including an increase in antioxidant activity, a decrease in pro-inflammatory cytokines, and the restoration of intestinal and liver tissue damage. In addition, Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 lead to changes in the structure of intestinal microbiota in aging mice. Specifically, there was a decrease in the abundance of the Cyanobacteria and an increase in the abundance of Akkermansia and Lactobacillus. More importantly, there was a significant increase in acetic acid, a short-chain fatty acid, due to intervention with the 2 strains. This increase might be attributed to higher Akkermansia. We show that the modulation of gut microbiota and metabolism in aging mice may be a promising strategy through which Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 might exert their anti-aging effects.
    Keywords:  Aging; Dogs; Gut microbiota; Inflammaging; Oxidative stress
    DOI:  https://doi.org/10.1016/j.crmicr.2025.100381
  8. J Agric Food Chem. 2025 Apr 17.
      Aging leads to progressive decline in the functions of cells, tissues, and organs, severely affecting muscle performance and overall health, highlighting the urgent need for effective therapeutic agents. This study investigated the antiaging properties of tricin, a flavonoid abundant in grains, using biological models, including human fibroblasts, Caenorhabditis elegans (C. elegans), and mice. Tricin significantly alleviated the senescent phenotype in human fibroblasts induced by D-galactose (D-gal), doxorubicin, and replicative senescence, as evidenced by reduced SA-β-gal activity, downregulated senescence markers (p16, p21), and decreased SASP factors. Mechanistically, tricin binds to AMPK and activates the AMPK-mTOR-p70S6K signaling pathway, promoting autophagy and delaying cellular aging. In vivo, tricin extended lifespan, enhanced stress resistance, and improved mobility in C. elegans through aak-2/AMPK-mediated autophagy. In D-gal-induced aging mice, tricin improved muscle function, reducing p16, p21, and SASP expression in muscle tissues. These findings underscore tricin's potential as a promising antiaging therapeutic via AMPK-mediated autophagy activation.
    Keywords:  AMPK; antiaging; autophagy; muscle function; tricin
    DOI:  https://doi.org/10.1021/acs.jafc.4c12619
  9. Theranostics. 2025 ;15(10): 4345-4367
      Background and Purpose: Vascular aging is a prior marker of human aging and a significant contributor to atherosclerosis and vascular calcification. However, there are limited pharmacological options available to mitigate vascular aging. Thus, understanding the mechanisms underlying vascular aging and age-related atherosclerosis and vascular calcification is crucial. This study investigates the targets of vascular aging and elucidates the role and mechanisms of Ganoderma lucidum spore powder (GLSP) in mitigating vascular aging and aging-associated atherosclerosis as well as vascular calcification. Methods: The anti-vascular aging effects of GLSP was determined in aged C57BL/6J mice and the targets of GLSP was identified through transcriptome sequencing. Additionally, the protective effects of GLSP on the aged vasculature were assessed by examining atherosclerosis in apoE-/- mice and vascular calcification in VD3 and nicotine-induced mice. In vitro, the protective effects of GLSP triterpenes against vascular aging and calcification was determined in vascular smooth muscle cells (VSMCs). Results: GLSP exerted anti-vascular aging effects by regulating the cell cycle and senescence-associated secretory phenotype (SASP), mitigating DNA damage, reducing oxidative stress, improving mitochondrial function and modulating metabolic levels. Furthermore, GLSP improved vascular aging-associated atherosclerosis and vascular calcification in vivo. Mechanistically, RNA sequencing revealed an upregulation of Sirt7 expression after GLSP treatment. Sirt7 inhibitor exacerbated VSMCs senescence and calcification in senescent VSMCs and abolished the anti-senescence and the inhibitory effect of GLSP triterpenes on VSMCs senescence and calcification. Innovatively, we found that Sirt7 interacted with Keap1 and facilitated Keap1 deacetylation, which promoted Keap1-Nrf2 dissociation and consequently enhanced Nrf2 nuclear translocation and activation. Conclusion: GLSP alleviates vascular aging by exerting antioxidant effects through the activation of the Sirt7-Nrf2 axis, providing a promising new strategy for delaying vascular aging, atherosclerosis and vascular calcification.
    Keywords:  GLSP; Nrf2; Sirt7; atherosclerosis; deacetylation.; vascular aging; vascular calcification
    DOI:  https://doi.org/10.7150/thno.110324
  10. Biochem Biophys Res Commun. 2025 Apr 15. pii: S0006-291X(25)00528-5. [Epub ahead of print]764 151814
       BACKGROUND: With the intensification of global aging, slowing down the aging process has become a topic of significant interest. Brain aging, as one of the prominent changes in the aging process, urgently requires the exploration of new therapeutic methods to delay its progression. Gastrodia, a traditional Chinese medicine, has been widely recognized for its medicinal value, particularly in its pronounced neuroprotective effects. Although previous studies have demonstrated the protective effects of Gastrodin (GAS), an active compound in Gastrodia, on the mouse nervous system, its underlying mechanisms remain unclear.
    OBJECTIVE: This study aims to investigate comprehensively the impact and mechanisms of GAS in delaying brain aging through the combined approach of network pharmacology and animal experiments, providing a theoretical basis for the clinical application of GAS in treating age-related decline.
    METHODS: A D-galactose (D-gal)-induced aging mouse model was employed, and the anti-aging effects of GAS were evaluated through behavioral experiments and morphological observations. A "compound-target-pathway" network was constructed using network pharmacology. Gene and protein expression related to potential targets and pathways were verified and analyzed using RT-qPCR and immunohistochemistry (IHC) methods.
    RESULTS: GAS exposure significantly alleviated signs of brain aging in mice, including reduced body weight index, improved behavioral memory, mitigation of hippocampal morphological damage due to aging, and relief of oxidative stress levels in the mouse brain. Target screening through network pharmacology identified four key targets related to the AMPK/mTOR pathway and autophagy: AMPK, ULK1, ATG5, and Beclin1. Validation of the network pharmacology results using RT-qPCR and IHC confirmed that GAS upregulates cellular autophagy levels through the AMPK/mTOR/ULK1 signaling pathway.
    CONCLUSION: GAS demonstrates a pronounced alleviating effect on age-related symptoms in D-galactose-induced brain aging mice by suppressing oxidative stress in the mouse brain. The mechanism involves the upregulation of cellular autophagy through the AMPK/mTOR/ULK1 signaling pathway.
    Keywords:  Autophagy; Brain aging; Gastrodin; Network pharmacology; Oxidative stress
    DOI:  https://doi.org/10.1016/j.bbrc.2025.151814
  11. Aging Dis. 2025 Apr 05.
      Aging is characterized by progressive multisystem deterioration driven by molecular and cellular mechanisms encapsulated in the twelve hallmarks of aging. Green tea (GT), derived from Camellia sinensis, has garnered significant scientific interest due to its rich polyphenolic composition, particularly epigallocatechin-3-gallate, and its pleiotropic health benefits. In this narrative review, we explored the multifaceted mechanisms through which GT may mitigate the aging hallmarks. Evidence from in vitro, animal, and human studies has shown that GT polyphenols can enhance DNA repair pathways, preserve telomere length, modulate epigenetic aging markers, improve proteostasis and autophagic flux, regulate nutrient-sensing networks, and rejuvenate mitochondrial function. Additionally, GT exhibits anti-inflammatory properties and may restore a physiological gut microbiota composition. Beyond molecular and cellular effects, GT consumption in humans has been associated with improved cognitive function, cardiovascular health, muscle preservation, and metabolic regulation in aging populations. Collectively, these findings highlight GT's potential as a naturally occurring geroscience intervention capable of addressing the interconnected network of aging processes more comprehensively than single-target pharmaceuticals. Future research should focus on optimizing dosing regimens, exploring synergies with other anti-aging strategies, and investigating personalized responses to GT interventions.
    DOI:  https://doi.org/10.14336/AD.2025.0398
  12. Biochim Biophys Acta Mol Basis Dis. 2025 Apr 12. pii: S0925-4439(25)00196-6. [Epub ahead of print]1871(6): 167851
      Mitochondrial dysfunction is a critical contributor to age-related functional declines in skeletal muscle and brain. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is essential for mitochondrial biogenesis and function during aging. While skeletal muscle-specific overexpression of PGC-1α is known to mimic exercise-induced benefits in young animals, its chronic systemic effects on aging tissues remain unclear. This study aimed to determine the lifelong impact of skeletal muscle-specific PGC-1α overexpression on mitochondrial health, oxidative stress, inflammation, and cognitive function in aged mice. We established three experimental groups: young wild-type mice (3-4 months old), aged wild-type mice (25-27 months old), and aged mice with skeletal muscle-specific PGC-1α overexpression (24-27 months old). In skeletal muscle, aging led to significant reductions in mitochondrial biogenesis markers, including PGC-1α, FNDC5, and mtDNA content. PGC-1α overexpression reversed this decline, elevating the expression of PGC-1α, SIRT1, LONP1, SDHA, CS, TFAM, eNOS, and mtDNA levels, suggesting preserved mitochondrial biogenesis. However, FNDC5 and SIRT3 were paradoxically suppressed, indicating potential compensatory feedback mechanisms. PGC-1α overexpression also enhanced anabolic signaling, as evidenced by increased phosphorylation of mTOR and S6, and reduced FOXO1 expression, favoring a muscle growth-promoting environment. Moreover, aging impaired mitochondrial dynamics by downregulating MFN1, MFN2, OPA1, FIS1, and PINK1. While PGC-1α overexpression did not restore fusion-related proteins, it further reduced fission-related protein and enhanced mitophagy proteins, as evidenced by increased PINK1 phosphorylation. In contrast, in the hippocampus, muscle-specific PGC-1α overexpression exacerbated age-associated mitochondrial biogenesis decline. Expression levels of key mitochondrial markers, including PGC-1α, SIRT1, CS, FNDC5, Cytochrome C, and TFAM, were further reduced compared to aged wild-type controls. mTOR phosphorylation was also significantly suppressed, whereas cognition-related proteins (BDNF, VEGF, eNOS) and performance in behavioral tests remained unchanged. Importantly, skeletal muscle-specific PGC-1α overexpression triggered pronounced oxidative stress and inflammatory responses in both skeletal muscle and the hippocampus. In skeletal muscle, elevated levels of protein carbonyls, IκB-α, NF-κB, TNF-α, SOD2, and NRF2 were observed, accompanied by a reduction in the DNA repair enzyme OGG1. Notably, similar patterns were detected in the hippocampus, including increased expression of protein carbonyls, iNOS, NF-κB, TNF-α, SOD2, GPX1, and NRF2, alongside decreased OGG1 levels. These findings suggest that the overexpression of PGC-1α in skeletal muscle may have contributed to systemic oxidative stress and inflammation. In conclusion, skeletal muscle-specific PGC-1α overexpression preserves mitochondrial biogenesis and enhances anabolic signaling in aging muscle but concurrently induces oxidative stress and inflammatory responses, which may adversely affect mitochondrial health in the brain. These results emphasize the complex role of the skeletal muscle PGC-1α during aging.
    Keywords:  Aging; Hippocampus; Inflammation; Mitochondrial biogenesis; Oxidative stress; PGC-1α; Skeletal muscle
    DOI:  https://doi.org/10.1016/j.bbadis.2025.167851
  13. Antioxidants (Basel). 2025 Feb 24. pii: 259. [Epub ahead of print]14(3):
      One of the major causes of senescence is oxidative stress caused by ROS, which is mainly generated from dysfunctional mitochondria. Strategies to limit mitochondrial ROS production are considered important for reversing senescence, but effective approaches to reduce them have not yet been developed. In this study, we screened the secondary metabolites that plants produce under oxidative stress and discovered sauchinone as a potential candidate. Sauchinone induced mitochondrial function recovery, enabling efficient electron transport within the electron transport chain (ETC). This led to a decrease in ROS production, a byproduct of inefficient electron transport. The reduction in ROS by sauchinone rejuvenated senescence-associated phenotypes. To understand the underlying mechanism by which sauchinone rejuvenates senescence, we carried out RNA sequencing and found VAMP8 as a key gene. VAMP8 was downregulated by sauchinone. Knockdown of VAMP8 decreased mitochondrial ROS levels and subsequently rejuvenated mitochondrial function, which was similar to the effect of sauchinone. Taken together, these studies revealed a novel mechanism by which sauchinone reduces mitochondrial ROS production by regulating mitochondrial function and VAMP8 expression. Our results open a new avenue for aging research to control senescence by regulating mitochondrial ROS production.
    Keywords:  ROS; mitochondria; mitochondrial oxidative stress; senescence amelioration
    DOI:  https://doi.org/10.3390/antiox14030259
  14. Pharmacol Ther. 2025 Apr 10. pii: S0163-7258(25)00062-2. [Epub ahead of print]270 108850
      Epigenetic modifications play a critical role in regulating gene expression under various physiological and pathological conditions. Epigenetic modifications reprogramming is a recognized hallmark of aging and a key component of the aging clock used to differentiate between chronological and biological age. The potential for prospective diagnosis and regulatory capabilities position epigenetic modifications as an emerging drug target to extend longevity and alleviate age-related organ dysfunctions. In the past few decades, numerous preclinical studies have demonstrated the therapeutic potential of natural products in various human diseases, including aging, with some advancing to clinical trials and clinical application. This review highlights the discovery and recent advancements in the aging clock, as well as the potential use of natural products as anti-aging therapeutics by correcting disordered epigenetic reprogramming. Specifically, the focus is on the imbalance of histone modifications, alterations in DNA methylation patterns, disrupted ATP-dependent chromatin remodeling, and changes in RNA modifications. By exploring these areas, new insights can be gained into aging prediction and anti-aging interventions.
    Keywords:  Aging; Aging clock; Epigenetic modifications; Longevity; Natural products
    DOI:  https://doi.org/10.1016/j.pharmthera.2025.108850
  15. Probiotics Antimicrob Proteins. 2025 Apr 17.
      Skin aging is influenced by structural alterations, oxidative stress, inflammation, and microbiome changes, and a comprehensive approach to addressing these factors may be effective for mitigating skin aging. This study evaluates the multifaceted anti-aging effects of heat-killed (HK-HN910) and lysed (LS-HN910) forms of Lactobacillus paragasseri HN910. Protective effects on cell viability, cell permeability, nitric oxide (NO) production, and skin anti-aging gene expression for both HK-HN910 and LS-HN910 were observed. Both forms significantly enhanced tight junction (TJ) protein zonula occludens- 1 (ZO- 1) and antioxidant enzyme glutathione peroxidase (GPx) gene expression, while significantly downregulating that of senescence-associated secretory phenotype pro-inflammatory cytokines interleukin (IL)- 1α, IL- 1β, IL- 6, IL- 8, and tumor necrosis factor-alpha (TNFα). LS-HN910 showed significantly greater upregulation of ZO- 1 and GPx and greater downregulation of IL- 1β and TNFα expression compared to HK-HN910. Cell wall component D-alanine (D-Ala) was released in higher amounts in LS-HN910 than in HK-HN910 and demonstrated anti-aging effects. D-Ala upregulated gene expression of skin barrier ZO- 1, claudin- 1 (Cla- 1), occludin (OCC), filaggrin (FLG), and sphingomyelin phosphodiesterase 2 (SMPD2) and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and GPx, while downregulating IL- 1α, IL- 1β, IL- 6, IL- 8, and TNFα. LS-HN910 treatment clinically revealed improvements in anti-aging parameters, including transepidermal water loss, skin water contents, sebum levels, dermal density, eye wrinkle index, skin pH, brightness, and microbiota composition, with a significant increase in Rhodococcus abundance. These findings indicate that LS-HN910, containing released D-Ala, is a promising cosmeceutical for preventing skin aging by enhancing the skin barrier, promoting oxidative defense, modulating inflammatory responses, and influencing skin microbiota.
    Keywords:   Lactobacillus paragasseri HN910; Cosmeceutical ingredient; D-Alanine; Skin anti-aging; Skin microbiome
    DOI:  https://doi.org/10.1007/s12602-025-10533-2
  16. Stem Cell Rev Rep. 2025 Apr 12.
      Expansion of adult stem cells in culture increases the percent of senescent cells, reduces their differentiation capacity and limits their clinical use. Here, we investigated whether treatment with certain senotherapeutic drugs would reduce the accumulation of senescent cells during expansion of human liver stem cells (HLSCs) while maintaining their differentiation capacity. Our results demonstrate that chronic treatment with the senomorphic XJB-5-131 or the senolytics cocktail D + Q reduced the number of senescent cells and significantly reduced the expression of senescence-associated genes and several inflammatory SASP factors in later passage HLSCs. Additionally, treatment with XJB-5-131 and D + Q improved the capacity of HLSCs to undergo osteogenic differentiation following extensive in vitro expansion. Overall, our data demonstrate that treatment with XJB-5-13 or D + Q results in a reduction in the percentage of replication-induced senescent HLSCs and likely other types of adult stem cells and improve the potential therapeutic use of later passage human stem cells.
    Keywords:  Cellular senescence; Human liver stem cells; Osteogenic differentiation; Senotherapeutics
    DOI:  https://doi.org/10.1007/s12015-025-10876-x
  17. Brain Nerve. 2025 Apr;77(4): 369-376
      The epigenome, a dynamic regulator of gene expression, has emerged as a key mediator of long-term cellular and organ functions. Beyond its classical role in gene regulation, the epigenome serves as a molecular "memory", capturing external environmental influences, such as lifestyle factors, obesity, and stress-induced DNA damage. Epigenomic memory can imprint persistent changes in cellular identity and functionality, thereby influencing aging and the onset of age-related diseases. Recent studies have revealed that early-life stress-induced DNA damage can accelerate aging by establishing epigenomic memory. However, strategies aimed at "rejuvenation", the targeted resetting of epigenomic information, are gaining traction for their potential to reverse aging phenotypes and treat diseases. This review explores the concept of the epigenome as a memory system, its role in aging, and emerging therapeutic approaches to rejuvenation.
    DOI:  https://doi.org/10.11477/mf.188160960770040369
  18. bioRxiv. 2025 Apr 04. pii: 2025.04.03.645994. [Epub ahead of print]
      Accumulation of cytosolic DNA has emerged as a hallmark of aging, inducing sterile inflammation. STING (Stimulator of Interferon Genes) protein translates the sensing of cytosolic DNA by cGAS (cyclic-GMP-AMP synthase) into an inflammatory response. However, the molecular mechanisms whereby cytosolic DNA-induced cGAS-STING pathway leads to aging remain poorly understood. We show that STING does not follow the canonical pathway of activation in human fibroblasts passaged (aging) in culture, senescent fibroblasts, or progeria fibroblasts (from Hutchinson Gilford Progeria Syndrome patients). Despite cytosolic DNA buildup, features of the canonical cGAS-STING pathway like increased cGAMP production, STING phosphorylation, and STING trafficking to perinuclear compartment are not observed in progeria/senescent/aging fibroblasts. Instead, STING localizes at endoplasmic reticulum, nuclear envelope, and chromatin. Despite the non-conventional STING behavior, aging/senescent/progeria cells activate inflammatory programs such as the senescence-associated secretory phenotype (SASP) and the interferon (IFN) response, in a cGAS and STING-dependent manner, revealing a non-canonical pathway in aging. Importantly, progeria/aging/senescent cells are hindered in their ability to activate the canonical cGAS-STING pathway with synthetic DNA, compared to young cells. This deficiency is rescued by activating vitamin D receptor signaling, unveiling new mechanisms regulating the cGAS-STING pathway in aging. Significantly, in HGPS, inhibition of the non-canonical cGAS-STING pathway ameliorates cellular hallmarks of aging, reduces tissue degeneration, and extends the lifespan of progeria mice. Our study reveals that a new feature of aging is the progressively reduced ability to activate the canonical cGAS-STING pathway in response to cytosolic DNA, triggering instead a non-canonical pathway that drives senescence/aging phenotypes.
    Significance Statement: Our study provides novel insights into the mechanisms driving sterile inflammation in aging and progeria. We reveal a previously unrecognized characteristic of aging cells: the progressive loss of ability to activate the canonical response to foreign or self-DNA at the cytoplasm. Instead, aging, senescent, and progeria cells activate inflammatory programs via a non-conventional pathway driven by cGAS and the adaptor protein STING. Importantly, pharmacological inhibition of the non-canonical cGAS-STING pathway ameliorates cellular, tissue and organismal decline in a devastating accelerated aging disease (Hutchinson Gilford Progeria Syndrome), highlighting it as a promising therapeutic target for age-related pathologies.
    DOI:  https://doi.org/10.1101/2025.04.03.645994
  19. CNS Neurosci Ther. 2025 Apr;31(4): e70392
       BACKGROUNDS: Dementia can impose a heavy economic burden on both society and families. Alzheimer's disease (AD), the most prevalent form of dementia, is a complex neurodegenerative disease characterized by the abnormal deposition of extracellular amyloid β-protein (Aβ) and the aggregation of intracellular Tau protein to form neurofibrillary tangles (NFTs). Given the limited efficacy of pharmacological treatment, scientists have already paid more attention to non-pharmacological strategies, including dietary restriction (DR). DR refers to a nutritional paradigm aimed at promoting overall health by modifying the balance between energy consumption and expenditure. Studies have demonstrated that DR effectively extends the healthy lifespan, delays the aging process, and achieves promising results in the prevention and treatment of AD in preclinical studies.
    METHODS: In this review we collected related studies and viewpoints by searching on PubMed database using the keywords. Most of the citations were published between 2015 and 2025. A few older literatures were also included due to their relevance and significance in this field.
    RESULTS: We first provide a concise overview of the current therapeutic and preventive strategies for AD. Then, we introduce several specific DR protocols and their favorable effects on AD. Furthermore, the potential mechanisms underlying the benefits of DR on AD are discussed. Finally, we briefly highlight the role of DR in maintaining brain health.
    CONCLUSION: This review may offer valuable insights into the development of innovative non-pharmacological strategies for AD treatment.
    Keywords:  Alzheimer's disease; calorie restriction; cognitive decline; dementia; dietary restriction; intermittent fasting; treatment
    DOI:  https://doi.org/10.1111/cns.70392
  20. BMC Complement Med Ther. 2025 Apr 12. 25(1): 137
       BACKGROUND: Aging is a physiological process that impacts multiple systems of organs. Alzheimer's disease (AD) is the most common form of dementia in the elderly, and it is a major problem in aging societies. The development of AD is linked to an accumulation of amyloid beta and Tau proteins, which impair cognition and cause memory loss.
    PURPOSE: We studied whether probiotics strains could protect and how effectively probiotics might delay age-related changes.
    METHODS: Two probiotics, Lactobacillus paracasei MSMC39-1 and Bifidobacterium animalis MSMC83 strain, were administered orally to mice beginning in middle age and continuing into aged mice. The mice were subsequently monitored and assessed for inflammation and oxidative stress in the colon, brain, and liver tissues, as well as for overall health, over a period of 16 weeks.
    RESULTS: We found aged mice received the combination of these probiotics showed a lower level of inflammatory markers and improved overall health compared to the control group. MSMC39-1 and MSMC83 enhance gut integrity and general well-being in aged mice and result in improved cognitive memory.
    CONCLUSION: Our findings suggest that these probiotics supplements may be particularly useful in strategies for the prevention of age-related pathologies by reducing inflammation and oxidative stress, which in turn would slow disease progression.
    CLINICAL TRIAL NUMBER: Not applicable.
    Keywords:  Aging; Anti-inflammation; Antioxidant; Cognitive function; Probiotics
    DOI:  https://doi.org/10.1186/s12906-025-04881-3
  21. Int J Biol Macromol. 2025 Apr 12. pii: S0141-8130(25)03585-8. [Epub ahead of print]309(Pt 4): 143033
      Lactoferrin (LF) has been shown to be effective in attenuating oxidative stress, neuroinflammation, but its potential and mechanisms in alleviating brain aging remain to be clarified. In this study, the effect of different doses of LF (L: 50, M: 500 and H: 2000 mg/kg) on D-galactose (D-gal)-induced brain aging C57BL/6 mice was evaluated. The results showed that body weight, mobility, and spatial memory capacity of aging mice were restored after LF (M & H) intervention. It also attenuated hippocampal neuronal damage and intestinal barrier damage in aging mice. LF (M & H) increased brain and serum levels of antioxidant defense enzymes (SOD, GSH, CAT) and decreased colon and serum levels of inflammatory factors (IL-1β, IL-6 and TNF-α). Western blotting results showed that LF (M & H) increased LC3II/I, Beclin1 expression, decreased p-mTOR, p-akt, and p62 expression, and restored autophagy through the PI3K/Akt/m-TOR pathway. Furthermore, LF (M & H) protected the intestinal barrier by regulating the ratio of Firmicutes/Bacteroidetes and increased levels of the beneficial metabolites short chain fatty acids (SCFAs). Notably, LF (H) exhibited the best anti-aging potential. 500 mg/kg/day LF intervention may be cost-effective in prevents brain aging by regulating the autophagy pathway and the microbiome-gut-brain axis.
    Keywords:  Lactoferrin antiaging; Microbiome-gut-brain axis; PI3K/Akt/m-TOR signaling pathway
    DOI:  https://doi.org/10.1016/j.ijbiomac.2025.143033
  22. Nat Metab. 2025 Apr 14.
      Animals select food based on hungers that reflect dynamic macronutrient needs, but the hormonal mechanisms underlying nutrient-specific appetite regulation remain poorly defined. Here, we identify tachykinin (Tk) as a protein-responsive gut hormone in Drosophila and female mice, regulated by conserved environmental and nutrient-sensing mechanisms. Protein intake activates Tk-expressing enteroendocrine cells (EECs), driving the release of gut Tk through mechanisms involving target of rapamycin (TOR) and transient receptor potential A1 (TrpA1). In flies, we delineate a pathway by which gut Tk controls selective appetite and sleep after protein ingestion, mediated by glucagon-like adipokinetic hormone (AKH) signalling to neurons and adipose tissue. This mechanism suppresses protein appetite, promotes sugar hunger and modulates wakefulness to align behaviour with nutritional needs. Inhibiting protein-responsive gut Tk prolongs lifespan through AKH, revealing a role for nutrient-dependent gut hormone signalling in longevity. Our results provide a framework for understanding EEC-derived nutrient-specific satiety signals and the role of gut hormones in regulating food choice, sleep and lifespan.
    DOI:  https://doi.org/10.1038/s42255-025-01267-0
  23. FASEB J. 2025 Apr 30. 39(8): e70542
      Skeletal muscle health and function deteriorate with age, ultimately leading to impaired mobility and disability. Exercise is among the most effective interventions to mitigate muscle dysfunction in aging and reverse deficits. However, low attrition and an impaired capacity to exercise may limit its utility in improving muscle function in aged persons. Therefore, it is crucial to advance our mechanistic understanding of the molecular transducers of exercise to identify new and innovative drug targets to improve muscle health. Transcriptomic profiling of the human response to exercise has revealed that the nuclear receptor NR4A3 (NOR-1) is among the most responsive genes to acute exercise. Previously, we observed that in vitro knockdown of NOR-1 alters metabolic signaling in C2C12 myotubes. Specifically, we found that expression of PERM1, CKMT2, myoglobin, and mTORC1 signaling were perturbed during the knockdown of NOR-1. Herein, we extend these findings and observe that a NOR-1-PERM1-myoglobin axis regulates myoglobin expression in vitro. Furthermore, we found that aging is associated with reduced skeletal muscle NOR-1 expression. Although it is well known that exercise improves aged muscle function, whether overexpression of the exercise-responsive gene NOR-1 can confer benefits and improve muscle function in an aged context has not been evaluated. We found that the overexpression of NOR-1 in aged muscle results in enhanced muscle endurance, mitochondrial respiration, and elevated expression of NOR-1 responsive genes that we previously identified in loss of function studies. However, we also observed that overexpression of NOR-1 did not improve maximal muscle torque production and resulted in a small but significant loss of muscle wet weight that was concomitant with elevated autophagy signaling. Our data suggest that NOR-1 expression may reduce muscle fatigability and that NOR-1 drives myoglobin expression in a PERM1-dependent manner.
    Keywords:  aging; autophagy; fatigue; mitochondria; muscle
    DOI:  https://doi.org/10.1096/fj.202500375R
  24. Antioxidants (Basel). 2025 Feb 21. pii: 249. [Epub ahead of print]14(3):
      Aging is associated with the accumulation of cellular damage due to oxidative stress and chronic low-grade inflammation, collectively referred to as "inflammaging". This contributes to the functional decline in various tissues, including the brain and skeletal system, which closely interplay. Mesenchymal stem cells (MSCs), known for their regenerative potential and ability to modulate inflammation, offer a promising therapeutic approach to counteract aging-related declines. In this study, we investigated the effects of homotaurine (a small molecule with neuroprotective properties) on MSCs and its effects on osteogenesis. We found that homotaurine treatment significantly reduced reactive oxygen species (ROS) levels, improved MSC viability, and modulated key stress response pathways, including the sestrin 1 and p21 proteins. Furthermore, homotaurine promoted osteogenesis and angiogenesis in zebrafish models by enhancing the expression of critical osteogenesis-associated genes, such as those coding for β-catenin and Runt-related transcription factor 2 (Runx2), and increasing the levels of the kinase insert domain receptor-like angiogenesis marker in aged zebrafish. In Parkinson's disease models using patient-specific midbrain organoids with the leucine-rich repeat kinase 2 G2019S mutation, homotaurine treatment enhanced β-catenin expression and reduced ROS levels, highlighting its potential to counteract the oxidative stress and dysfunctional signaling pathways associated with neurodegeneration. Our findings suggest that homotaurine not only offers neuroprotective benefits but also holds promise as a dual-target therapeutic strategy for enhancing both neuronal and bone homeostasis in aging and neurodegenerative diseases.
    Keywords:  Parkinson’s disease; homotaurine; mesenchymal stem cells; reactive oxygen species
    DOI:  https://doi.org/10.3390/antiox14030249
  25. Geroscience. 2025 Apr 12.
      We have previously reported that when autophagy is suppressed in endothelial cells (ECs), a glycolytic defect limits shear-stress -induced ATP production to an extent that purinergic 2Y1 receptor (P2Y1R)-mediated activation of EC nitric oxide (NO) synthase (eNOS) is compromised. Subsequently we demonstrated the functional relevance of this finding in arteries from mice with genetic, pharmacological, and age-associated EC autophagy impairment. Using gain and loss of function approaches in vitro, we further revealed that p-PKCδT505 serves as a signaling link between P2Y1R activation and NO generation. Here we sought to discern the functional relevance of this observation. First, shear-stress- induced activating phosphorylation of eNOS (p-eNOSS1177) that is otherwise prevented by knockdown of autophagy-related gene 3 (Atg3) in ECs was restored by the PKC agonist bryostatin-1. Next, in murine models of genetic and age-associated EC autophagy compromise, depressed vasodilation displayed by femoral and cerebral arteries was reversed by bryostatin-1 in a manner that could be prevented by concurrent NO synthase inhibition. Finally, the bryostatin-1-mediated normalization of intraluminal flow-induced vasodilation observed in femoral arteries from both models of EC autophagy disruption was mitigated by inhibiting downstream targets of p-PKCδT505 i.e., p-PKDS744/S748 and p-PKDS916. These findings provide evidence that stimulating PKC/PKD has strategic potential to restore compromised endothelial function in pathologies associated with suppressed EC autophagy e.g., aging.
    Keywords:  Aging; Bryostatin-1; Endothelial cell; Nitric oxide
    DOI:  https://doi.org/10.1007/s11357-025-01650-5
  26. Food Funct. 2025 Apr 15.
      At the neuromuscular junction (NMJ), which coordinates movement, postsynaptic-derived neurotrophic factors have neuroprotective functions and retrogradely regulate the exocytotic machinery involved in neurotransmitter release. In parallel, presynaptic autocrine muscarinic signaling plays a fundamental modulatory role in this synapse. We previously found that these signaling pathways are impaired in the aged neuromuscular system. In this follow-up study, we investigated an anti-aging strategy using grape seed procyanidin extract (GSPE), a common dietary antioxidant known for its neuroprotective properties in various pathologies, but its effects on the aged neuromuscular system remain unexplored. This study analyses whether GSPE can mitigate age-associated impairments in neurotrophic and muscarinic signaling within the neuromuscular system. We assessed the expression (protein levels) and activation (phosphorylation) of the key proteins in the brain-derived-neurotrophic-factor (BDNF)/neurotrophin 4 (NT-4) and muscarinic pathways in the extensor digitorum longus (EDL) muscles of aged rats, with comparisons to GSPE-treated aged rats and young controls. The results demonstrate that GSPE treatment prevents the most relevant aging-induced changes in neurotrophic and muscarinic receptor isoforms, downstream protein kinases, and their targets in the neurotransmitter exocytotic machinery. Nevertheless, GSPE was less effective at preventing alterations in some other proteins within these pathways, such as calcium channels, and did not modify several other molecules involved in these pathways, which remain unchanged during aging. Overall, this study highlights the neuroprotective potential of GSPE in preventing fundamental age-related molecular changes at the NMJ, which helps improve functionality and may increase the quality of life and lifespan in aged individuals.
    DOI:  https://doi.org/10.1039/d5fo00286a
  27. Sci Rep. 2025 Apr 16. 15(1): 13053
      Most living organisms experience time-dependent functional deterioration as they age. To combat aging, aspirin was proposed as an already well-studied drug. However, its antiaging effect is neither well studied nor understood. So, this study intended to assess the proposed antiaging effect of aspirin. Three groups of seven adult male albino rats were established. The control group received saline, the aging model group got a daily single D-galactose subcutaneous injection (300 mg/kg), and the aspirin group consisted of D-galactose-induced aged rats that received a daily aspirin oral dose (60 mg/kg). Drugs were given for 8 weeks. Then, malondialdehyde (MDA) blood level was evaluated, and rats were euthanized. Buccal mucosa samples were obtained for inducible nitric oxide synthase (iNOS) gene expression, histopathological, ultrastructural, and comet analyses. MDA blood level, iNOS gene expression and DNA damage examined by comet assay displayed a significant reduction in the aspirin group when compared to the aging model group. Histopathological and ultrastructural results showed that aspirin ameliorated most of the degenerative signs caused by D-galactose. Thus, it was deduced that aspirin had promising results as an antiaging pharmaceutical agent. However, more studies are needed regarding its translation to human trials.
    Keywords:  Antiaging; Aspirin; Buccal mucosa; Comet assay; iNOS
    DOI:  https://doi.org/10.1038/s41598-025-94566-1
  28. J Control Release. 2025 Apr 10. pii: S0168-3659(25)00330-X. [Epub ahead of print]382 113710
      Age-related diseases imposed heavy burdens to the healthcare systems globally, while cell senescence served as one fundamental molecular/cellular basis for these diseases. How to tackle the senescence-relevant problems is a hotspot for biomedical research. In this review article, the hallmarks and molecular pathways of cell senescence were firstly discussed, followed by the introduction of the current anti-senescence strategies, including senolytics and senomorphics. With suitable physical or chemical properties, multiple types of nanomaterials were used successfully in senescence therapeutics, as well as senescence detection. Based on the accumulating knowledges for senescence, the rules of how to use these nanoplatforms more efficiently against senescence were also summarized, including but not limited to surface modification, material-cargo interactions, factor responsiveness etc. The comparison of these "senescence-selective" nanoplatforms to other treatment options (prodrugs, ADCs, PROTACs, CART etc.) was also given. Learning from the past, nanotechnology can add more choice for treating age-related diseases, and provide more (diagnostic) information to further our understanding of senescence process.
    Keywords:  Aging; Cell signaling; Controlled release; Imaging; Senescence; Targeted therapy
    DOI:  https://doi.org/10.1016/j.jconrel.2025.113710
  29. Healthcare (Basel). 2025 Apr 06. pii: 834. [Epub ahead of print]13(7):
      Aging has been thought to be factual, inherited, and obligatory. However, aging can be divided into primary (i.e., inevitable physiological changes) and secondary (i.e., age-associated changes driven by life choices, environment, and society) aging. The impact of social norms and life choices is why no two 70-year-olds look the same. The life choice that appears to have the strongest impact on aging is physical activity. Research continues to highlight the power of mitigating age-related losses via physical activity and debunking the notion that age-related changes such as falls, frailty, and functional decline are inevitable. Physiotherapists are the healthcare professionals who reverse or slow down age-related changes and prevent secondary aging from occurring. Physiotherapists are the health profession's experts in movement science, whose interventions primarily center around physical activity as medicine. Thus, physiotherapists function as pharmacists of physical activity and are well-positioned to prescribe the dosages needed for wellness promotion as well as disease prevention and management. This paper provides guidance from the perspective of the physiotherapist on exercise prescription most optimal and consumable for an older population.
    Keywords:  aging; behavior change; exercise; frailty; physical activity; physical therapy; physiotherapy
    DOI:  https://doi.org/10.3390/healthcare13070834
  30. Nat Mater. 2025 Apr 17.
      Stem cell therapy is a promising approach for tissue regeneration after traumatic injury, yet current applications are limited by inadequate control over the fate of stem cells after transplantation. Here we introduce a bioconstruct engineered for the staged release of growth factors, tailored to direct different phases of muscle regeneration. The bioconstruct is composed of a decellularized extracellular matrix containing polymeric nanocapsules sequentially releasing basic fibroblast growth factor and insulin-like growth factor 1, which promote the proliferation and differentiation of muscle stem cells, respectively. When applied to a volumetric muscle loss defect in an animal model, the bioconstruct enhances myofibre formation, angiogenesis, innervation and functional restoration. Further, it promotes functional muscle formation with human or aged murine muscle stem cells, highlighting the translational potential of this bioconstruct. Overall, these results highlight the potential of bioconstructs with orchestrated growth factor release for stem cell therapies in traumatic injury.
    DOI:  https://doi.org/10.1038/s41563-025-02212-y
  31. Phytomedicine. 2025 Mar 31. pii: S0944-7113(25)00350-2. [Epub ahead of print]141 156710
       BACKGROUND: Aging-related liver and brain damage caused by oxidative stress and inflammation significantly impacts health and quality of life. Natural bioactive compounds, such as 6'-O-caffeoylarbutin (CA), which is primarily distributed in Vaccinium species, have been studied for their antioxidant and anti-inflammatory properties. This study aims to investigate the protective effect on liver and brain damage induced by D-galactose (D-gal) in mice and to explore its potential molecular mechanisms.
    PURPOSE: This study aims to investigate the protective effects of CA on D-galactose (D-gal)-induced liver and brain damage in mice and to explore its potential molecular mechanisms.
    METHODS: CA was prepared from Vaccinium dunalianum and identified using UHPLC-ESI-HR-MS/MS. Molecular docking and network pharmacology analysis were performed to predict the binding of CA with SIRT1 and NF-κB1 targets. In vivo, a D-gal-induced aging mouse model was established to evaluate the biochemical, oxidative stress, and inflammatory parameters. The effects of CA on oxidative stress and inflammation were examined through enzymatic activity assays, cytokine level measurements, and histopathological analysis. Western blotting was used to validate the involvement of the SIRT1/NF-κB pathway.
    RESULTS: CA treatment significantly alleviated liver and brain damage in D-gal-induced mice by decreasing AChE, AST, and ALT activities, improving organ indices, and reducing histopathological alterations. CA enhanced antioxidant defense by increasing SOD, CAT, and T-AOC activities, elevating GSH levels, and decreasing MDA content. Furthermore, CA suppressed the inflammatory response by downregulating IL-6 and TNF-α levels. Mechanistically, CA inhibited NF-κB p65 phosphorylation and suppressed iNOS and COX-2 expression, likely via activation of the SIRT1 protein.
    CONCLUSION: This study demonstrates that CA protects against D-gal-induced oxidative stress and inflammation in liver and brain tissues via the SIRT1/NF-κB pathway, supporting its potential as a bioactive compound for preventing aging-related liver and brain damage.
    Keywords:  6′-O-caffeoylarbutin; SIRT1/NF-кB signalling pathway; inflammation; network pharmacology; oxidative stress
    DOI:  https://doi.org/10.1016/j.phymed.2025.156710
  32. Geroscience. 2025 Apr 12.
      Sarcopenia, defined as the progressive loss of skeletal muscle mass and function associated with ageing, has devastating effects in terms of reducing the quality of life of older people. Muscle ageing is characterised by muscle atrophy and decreased capacity for muscle repair, including a reduction in the muscle stem cell pool that impedes recovery after injury. Histone deacetylase 11 (HDAC11) is the newest member of the HDAC family and it is highly expressed in skeletal muscle. Our group recently showed that genetic deficiency in HDAC11 increases skeletal muscle regeneration, mitochondrial function and globally improves muscle performance in young mice. Here, we explore for the first time the functional consequences of HDAC11 deficiency in old mice, in homeostasis and during muscle regeneration. Aged mice lacking HDAC11 show attenuated muscle atrophy and postsynaptic fragmentation of the neuromuscular junction, but no significant differences in the number or diameter of myelinated axons of peripheral nerves. Maintenance of the muscle stem cell reservoir and advanced skeletal muscle regeneration after injury are also observed. HDAC11 depletion enhances mitochondrial fatty acid oxidation and attenuates age-associated alterations in skeletal muscle fatty acid composition, reducing drastically the omega-6/omega-3 fatty acid ratio and improving significantly the omega-3 index, providing an explanation for improved muscle strength and fatigue resistance and decreased mortality. Taken together, our results point to HDAC11 as a new target for the treatment of sarcopenia. Importantly, selective HDAC11 inhibitors have recently been developed that could offer a new therapeutic approach to slow the ageing process.
    Keywords:  Fatty acid oxidation; HDAC11; Muscle atrophy; Omega-6/omega-3 fatty acid ratio; Sarcopenia; Skeletal muscle regeneration
    DOI:  https://doi.org/10.1007/s11357-025-01611-y
  33. Toxicol Res (Camb). 2025 Apr;14(2): tfaf055
      Fine particulate matter (PM2.5) exposure is significantly linked to lung epithelial cell senescence, and autophagy dysfunction being a key contributor to the aging process. Although the anti-aging properties of ellagic acid (EA) are well-documented, its specific protective effect on PM2.5-induced lung epithelial cell senescence still needs to be studied in depth. To investigate the impacts of PM2.5 on autophagy and senescence in lung epithelial cells, 16HBE and A549 cells were exposed to PM2.5 suspension. Additionally, to explore the potential intervention effect of EA, cells were pretreated with EA before exposure to PM2.5 suspension. Cell morphology, proliferation, senescence-related markers, senescence-associated secretory phenotype (SASP), and autophagy-related markers were then assessed. Our results showed that the proliferation of 16HBE and A549 cells were inhibited and autophagy dysfunction and senescence were induced under PM2.5 exposure. However, pretreatment with EA can significantly improve the obstruction of autophagy flux caused by PM2.5, thereby effectively alleviating cell senescence. This study reveals the mechanism by which PM2.5 induces senescence in lung epithelial cells and confirms the protective role of ellagic acid in this process.
    Keywords:  PM2.5lung epithelial cells; autophagy; ellagic acid; senescence
    DOI:  https://doi.org/10.1093/toxres/tfaf055
  34. J Ethnopharmacol. 2025 Apr 13. pii: S0378-8741(25)00491-X. [Epub ahead of print] 119807
       ETHNOPHARMACOLOGICAL RELEVANCE: Aging contributes to various pathologies, including kidney injury, but the therapeutic potential of natural drugs in these contexts remains inadequately assessed. The roots of Panax ginseng C.A. Meyer, a widely used traditional Chinese medicine, are reputed for their anti-aging properties and life-prolonging effects, yet their specific medicinal components and mechanisms of action require further exploration.
    AIM OF STUDY: This study compared the pharmacological effects of ginsenoside Rg2 (Rg2), 20(S)-protopanaxatriol (PPT) and arginyl-fructosyl glucose (AFG) on aging-related kidney injury, aiming to identify their relative efficacy and potential mechanisms of action.
    MATERIALS AND METHODS: SAMP8 mice, which exhibit an accelerated aging phenotype, were treated daily with Rg2, PPT or AFG for eight weeks. Kidney function markers were evaluated, and histopathological analysis was performed. Additionally, mRNA and protein expression levels were analyzed using Real-time qPCR and western blot methods to investigate the involvement of IGF-1/mTOR, PI3K/AKT and MAPK/ERK signaling pathways.
    RESULTS: Rg2, PPT and AFG all significantly improved kidney function and aging markers, ameliorated histological changes, and exhibited anti-inflammatory, antioxidant and anti-apoptotic effects. Among all compounds, Rg2 had the most significant effect on basic renal function indicators. In addition, Rg2 and PPT significantly affected AMPK family proteins, mTOR and IGF-1 transcription factors, highlighting their regulatory activities through insulin /IGF-1 and mTOR signaling pathways, and AFG significantly regulates PI3K/AKT signaling pathways.
    CONCLUSION: The findings indicate that Rg2, PPT and AFG may prevent aging-related kidney diseases by targeting IGF-1/mTOR and PI3K/AKT signaling pathway. These results highlight their potential for further investigation to treat aging-related kidney diseases.
    Keywords:  AFG; PPT; Rg2; aging; kidney injury; mitochondrial dysfunction
    DOI:  https://doi.org/10.1016/j.jep.2025.119807
  35. Antioxidants (Basel). 2025 Feb 26. pii: 272. [Epub ahead of print]14(3):
      Currently, nutraceuticals and functional food/cosmeceutical sectors are seeking natural molecules to develop various types of phytopharmaceutical products. Flavonoids have been reported in antioxidant and many medical/pharmacological activities. Monochoria angustifolia or Siam violet pearl medicinal plant is the newest species of the genus Monochoria C. Presl, which have long been consumed as food and herbal medicines. Though previous work showed that apigenin-7-O-glucoside is the most abundant antioxidant phytochemical found in this medicinal plant, the report on anti-aging activity is still lacking and needs to be filled in. The objective of this work is to explore anti-aging capacities of the most abundant antioxidant phytochemical reported in this plant using both in silico and in vitro assessments. In addition, pharmacokinetic properties were predicted. Interestingly, the results from both in silico and in vitro analysis showed a similar trend that apigenin-7-O-glucoside is a potential anti-aging agent against three enzymes. The pharmacokinetic properties, such as adsorption, distribution, metabolism, excretion and toxicity (ADMET), of this compound are also provided in this work. The current study is also the first report on anti-aging properties of this Thai medicinal plant. However, the safety and efficacy of future developed products from this compound and clinical study should be determined in the future.
    Keywords:  Monochoria angustifolia; anti-aging; flavone; flavonoids; medical benefits; medicinal plants; molecular modeling; pharmacological activity
    DOI:  https://doi.org/10.3390/antiox14030272
  36. Int J Nanomedicine. 2025 ;20 4571-4587
       Introduction: Topical application of 17β-estradiol (E2) has been shown to improve various hallmark features of skin aging, including enhancing skin elasticity and hydration, reducing wrinkles, and promoting collagen synthesis. However, the role of estrogen in UVB-induced photoaging of the skin remains unclear. Furthermore, E2's clinical application is limited by issues such as bioavailability and potential adverse effects. Therefore, this study aims to explore the role of E2 in UVB-induced skin photoaging and to prepare a gold (Au)@mesoporous polydopamine (mPDA)-hyaluronic acid (HA)/carboxymethyl chitosan (CMCS) nanoparticle composite hydrogel (Au/E2@mPDA-HCG) for the treatment of skin photoaging.
    Methods: This study successfully fabricated mPDA with a well-defined mesoporous structure and incorporated Au NPs into the mesopores of mPDA using an in situ growth method, thereby constructing Au@mPDA NPs loaded with E2. Subsequently, the Au/E2@mPDA NPs were embedded into a HA/CMCS hydrogel to develop the Au/E2@mPDA-HCG nanoparticle composite hydrogel. The composite hydrogel was characterized through in vitro and in vivo experiments, and its efficacy in improving skin photoaging was evaluated.
    Results: This study revealed that estrogen deficiency significantly exacerbates UVB-induced skin photoaging, likely through mechanisms closely associated with increased oxidative stress and reduced collagen production. Moreover, the Au/E2@mPDA-HCG nanoparticle composite hydrogel demonstrated favorable morphological characteristics and biocompatibility. In vitro and in vivo experimental results indicated that this composite hydrogel effectively enhanced the therapeutic efficacy of E2 in treating skin photoaging, as evidenced by its significant mitigation of oxidative stress and inflammatory responses, along with the promotion of collagen synthesis.
    Conclusion: In conclusion, this study suggests that the combination of E2 with Au@mPDA@HCG nanocomposite hydrogel offers a promising therapeutic strategy for UVB-induced skin photoaging.
    Keywords:  Au nanoparticle; estrogen; hyaluronic acid /carboxymethyl chitosan hydrogel; mesoporous polydopamine; skin photoaging
    DOI:  https://doi.org/10.2147/IJN.S511388