bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2025–04–13
38 papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño



  1. Nat Commun. 2025 Apr 08. 16(1): 3340
      Longevity research aims to extend the healthspan while minimizing the duration of disability and morbidity, known as the sickspan. Most longevity interventions in model organisms extend healthspan, but it is not known whether they compress sickspan relative to the lifespan. Here, we present a theory that predicts which interventions compress relative sickspan, based on the shape of the survival curve. Interventions such as caloric restriction that extend mean lifespan while preserving the shape of the survival curve, are predicted to extend the sickspan proportionally, without compressing it. Conversely, a subset of interventions that extend lifespan and steepen the shape of the survival curve are predicted to compress the relative sickspan. We explain this based on the saturating-removal mathematical model of aging, and present evidence from longitudinal health data in mice, Caenorhabditis elegans and Drosophila melanogaster. We apply this theory to identify potential interventions for compressing the sickspan in mice, and to combinations of longevity interventions. This approach offers potential strategies for compressing morbidity and extending healthspan.
    DOI:  https://doi.org/10.1038/s41467-025-57807-5
  2. Aging Cell. 2025 Apr 08. e70058
      Dietary restriction (DR) is a well-established method for extending lifespan across various species, including C. elegans. Among the different DR regimens, axenic dietary restriction (ADR), in which worms are grown in a nutrient-rich sterile liquid medium, yields the most powerful lifespan extension. However, the molecular mechanisms underlying this longevity phenotype remain largely unexplored. Through a pilot screen of candidate genes, we identified the proprotein convertase BLI-4 as a crucial factor in neurons for modulating lifespan under ADR conditions. BLI-4's role appears to be specific to ADR, as it does not significantly impact longevity under other DR regimens. We further explored the involvement of different bli-4 isoforms and found that isoforms b, f, i and j redundantly contribute to the ADR-mediated lifespan extension, while the bli-4d isoform is mainly involved in development. Proteomics analysis revealed that the loss of BLI-4 function under ADR conditions specifically downregulates GOLG-2, involved in Golgi complex organization. This gene also partially mediates the longevity effects of BLI-4 under ADR conditions. Our findings highlight the importance of neuronal BLI-4 and its downstream targets in regulating lifespan extension induced by ADR in C. elegans.
    Keywords:   Caenorhabditis elegans ; BLI‐4; axenic dietary restriction (ADR); longevity; neuropeptide signaling; proprotein convertase; proteomics
    DOI:  https://doi.org/10.1111/acel.70058
  3. Res Sq. 2025 Mar 28. pii: rs.3.rs-6173768. [Epub ahead of print]
      Biological aging drives cellular dysfunction and human disease, yet studying human-specific aging dynamics remains challenging due to limited experimental platforms. Here we show that long-term post-mitotic culture of human fibroblasts authentically recapitulates and accelerates in-vivo aging signatures. Longitudinal paired transcriptomic-epigenetic analyses revealed that in-vitro aging mirrors in-vivo primary fibroblasts aging, with concordant transcriptional aging pathways and accelerated epigenetic clock aging patterns. Direct neuronal conversion of pre-aged fibroblasts preserved biological age, enabling pseudo-longitudinal modeling of neuronal aging. Single-cell transcriptomics revealed a time-dependent increase in age-heterogeneity, reflecting in-vivo observations and revealing heterogeneity driven by the variable loss of transcriptional programs. Using this accelerated aging platform, we evaluated anti-aging compounds: Metformin broadly halted transcriptomic and epigenetic aging, while Rapamycin showed limited efficacy. These findings align with clinical evidence, demonstrating our platform's capacity to predict therapeutic anti-aging efficacy with molecular resolution. This system advances our understanding of aging mechanisms and facilitates the development of interventions against age-related diseases.
    DOI:  https://doi.org/10.21203/rs.3.rs-6173768/v1
  4. J Invest Dermatol. 2025 Apr 08. pii: S0022-202X(25)00395-1. [Epub ahead of print]
      Skin tissue, which consists of epidermal, dermal, and hypodermal cells, plays an important role in biological defense and physical appearance. External and internal stresses occurring with aging disrupt skin homeostasis, promoting development of phenotypes associated with aging. While many studies of skin aging focus on the dermis, potential epidermal changes have largely remained uncharacterized. Here, we demonstrate that epidermal cells do not exhibit cellular senescence phenotypes with aging but instead show age-related decreases in mitochondrial number. We also found that mice lacking mitochondrial transcription factor A (TFAM) in epidermal cells exhibit delayed hair regrowth and impaired wound healing by middle age resembling changes seen in skin of aged mice. Furthermore, middle-aged epidermis-specific TFAM-deficient mice exhibited obesity, suggesting that impaired fatty acid metabolism in epidermal cells resulting from mitochondrial decline may lead to obesity. These findings overall suggest that mitochondrial decline occurs as a primary event in epidermal aging, and that anti-aging strategies to enhance activity or number of epidermal mitochondria could antagonize both skin-aging phenotypes and age-related metabolic disease.
    Keywords:  aging; mitochondria; obesity
    DOI:  https://doi.org/10.1016/j.jid.2025.03.028
  5. Actas Dermosifiliogr. 2025 Apr 04. pii: S0001-7310(25)00221-2. [Epub ahead of print]
      Skin aging is a complex, continuous, multifactorial process resulting from cumulative morphological and functional changes in the skin over time. This happens because of 2 processes: intrinsic and extrinsic skin aging. Intrinsic skin aging occurs naturally over time and reflects each person's genetic makeup, or heredity. Extrinsic skin aging, on the other hand, is due to exposomal factors, such as solar radiation, air pollution, tobacco or nutrition, being the first 2 the most important of all. Exposure to air pollutants, primarily gases such as ground-level ozone and particulate matter, can accelerate the process via 4 key mechanisms: reactive oxygen species generation, inflammation, skin microbiome disruption, and aryl hydrocarbon receptor activation. Regarding solar radiation, all wavelengths reaching the Earth's surface have an impact on the skin, having a synergistic effect with air pollution ("photo-pollution"). Here, we discuss this phenomenon and mitigation strategies, including sunscreens, cosmetics with film-forming plus antioxidant ingredients, and oral supplementation.
    Keywords:  Envejecimiento de la piel; Skin aging; air pollution; anti-pollution; anticontaminación; contaminación del aire; exposoma; exposome; radiación solar; solar radiation
    DOI:  https://doi.org/10.1016/j.ad.2025.04.005
  6. Aging Cell. 2025 Apr 07. e70050
      Aging is an inevitable biological process, driven in part by increased oxidative stress, which accelerates cellular damage and contributes to immune system dysfunction. Therefore, targeting oxidative stress has emerged as a potential strategy. Pyrroloquinoline quinone (PQQ), a potent antioxidant, has demonstrated significant efficacy in reducing oxidative stress and modulating immune responses, making it a promising therapeutic candidate. In this study, we investigated the effects of aging on the hematopoietic immune system (HIS) through single-cell RNA sequencing (scRNA-seq) of spleen and bone marrow cells in murine models. Our results revealed widespread age-related inflammation and oxidative stress within immune cell populations. Notably, long-term PQQ supplementation improved physiological parameters and reduced blood inflammatory factors levels in aged mice. Subsequent scRNA-seq analysis demonstrated that PQQ supplementation effectively reduced oxidative stress levels across various HIS cell types and reversed aging-related phenotypes, such as inflammatory responses and immunosenescence. Additionally, PQQ reversed aging-induced disrupted signaling and restored immune homeostasis, particularly in B cells and hematopoietic stem cells (HSCs). Importantly, we identified critical molecular targets, including ASPP1, which mediates PQQ's anti-apoptotic effects in B cells, and Yy1 and CD62L, which were upregulated by PQQ to restore HSCs self-renewal and differentiation potential. Furthermore, the machine learning program and experimental validation demonstrated the senolytic and senomorphic effects of PQQ in vivo and vitro. These findings underscore PQQ's potential not only in mitigating oxidative stress but also in restoring immune homeostasis and promoting cellular regeneration, highlighting its therapeutic potential in addressing immune aging and improving physiological function.
    Keywords:  aging; hematopoietic immune system; oxidative stress; pyrroloquinoline quinone; senescent cells
    DOI:  https://doi.org/10.1111/acel.70050
  7. Mech Ageing Dev. 2025 Apr 06. pii: S0047-6374(25)00032-6. [Epub ahead of print] 112056
      The selective eradication of senescent cells using senolytic compounds represents a promising strategy to treat senescence-associated diseases like aging and cancer. However, many senolytics may cause systemic toxicity. Magkouta et al., writing in Nature Aging, introduced mGL392, an advanced senolytic platform utilizing a lipofuscin-binding domain scaffold conjugated with a senolytic drug (e.g., dasatinib). mGL392 effectively eliminates senescent cells in vitro and in vivo, reducing tumor size in melanoma models while minimizing systemic toxicity. Compared to existing senolytics, it offers improved specificity, reducing off-target effects. This innovation presents a safer and more effective approach for treating senescence-related diseases.
    Keywords:  aging and cancer; cellular senescence; senescent cells eradication; senolytic platform
    DOI:  https://doi.org/10.1016/j.mad.2025.112056
  8. Biogerontology. 2025 Apr 04. 26(2): 88
      Skeletal muscle aging, characterized by progressive declines in muscle mass and strength, correlates with reduced quality of life and increased mortality. Resistance exercise is known to be critical for maintaining skeletal muscle health. This study investigated the effects of aging and resistance exercise on muscle strength, physiological properties, longevity proteins, and telomere length in mice. Twenty-eight-week-old senescence-accelerated mouse prone 8 (SAMP8) mice were used as a model for muscle aging, with senescence-accelerated mouse resistant 1 (SAMR1) mice serving as healthy controls. The mice underwent a 12-week regimen of ladder-climbing training, a form of resistance exercise, performed three days per week. After the training, muscle strength and muscle weight were measured. Levels of the longevity proteins adenosine monophosphate-activated kinase (AMPK), mammalian target of rapamycin (mTOR), and sirtuin 1 (SIRT1) were assessed via western blotting, and telomere length was evaluated by qPCR. SAMP8 mice exhibited significantly lower muscle mass and strength than SAMR1 mice, while resistance exercise attenuated these deficits in SAMP8 mice. SAMP8 mice showed elevated AMPK phosphorylation and SIRT1 levels compared to SAMR1 mice; resistance exercise normalized AMPK phosphorylation levels to approximate those of SAMR1 mice. mTOR activity was significantly reduced in SAMP8 mice but tended to be restored by resistance exercise. Telomere length remained unchanged in SAMP8 mice after resistance exercise compared to their sedentary controls. In conclusion, aging reduces muscle function and disrupts levels of longevity proteins. Resistance exercise mitigates these effects by improving muscle function and restoring molecular balance.
    Keywords:  Longevity proteins; Muscle aging; Resistance exercise; Sarcopenia; Telomere length
    DOI:  https://doi.org/10.1007/s10522-025-10234-x
  9. J Biosci. 2025 ;pii: 20. [Epub ahead of print]50
      The insulin/IGF-I-like signaling (IIS) pathway is a highly conserved signaling cascade that plays a crucial role in regulating longevity across species. Given its significance in aging, identifying novel kinases interacting with the IIS pathway can provide deeper insights into the mechanisms governing longevity. In this study, we performed a targeted RNAi screening of the Caenorhabditis elegans kinome, using dauer formation as a phenotypic readout. We identified several known and novel kinase modulators of the IIS pathway. These hits were enriched with both previously documented and undocumented lifespan regulators. Thermotolerance assays revealed mixed trends, with some kinase inhibitions increasing while others decreasing protection against thermal stress. We observed a positive correlation between thermotolerance and lifespan extension, as well as between dauer formation and lifespan extension, with thermotolerance proving to be a better predictor of longevity. Our findings offer a valuable resource for researchers exploring the IIS pathway and highlight novel, unannotated kinases as potential new therapeutic targets for aging interventions.
  10. J Food Drug Anal. 2025 Mar 31. 33(1): 1-12
      Apples, a ubiquitous and beloved fruit, harbor a treasure trove of bioactive compounds, with apple polyphenols (APs) taking center stage. This review delves into the latest scientific advancements illuminating the anti-cancer and anti-aging properties of APs. We dissect the intricate mechanisms by which APs combat cancer initiation, progression, and metastasis, highlighting their prowess in inducing apoptosis, inhibiting angiogenesis, and modulating cell signaling pathways. Furthermore, we explore the multifaceted ways APs combat aging, including their potent antioxidant and anti-inflammatory actions, DNA protective effects, and ability to modulate cellular processes like autophagy and metabolism. This comprehensive review underscores the therapeutic promise of APs in promoting healthy aging and combating age-related diseases like cancer.
    DOI:  https://doi.org/10.38212/2224-6614.3539
  11. Phytomedicine. 2025 Apr 01. pii: S0944-7113(25)00354-X. [Epub ahead of print]141 156714
      Silicosis, an age-related disease, is still a heavy burden on global occupational health. Emerging evidence has revealed that targeting senescent cells may be a promising therapeutic strategy for silicosis. This study was designed to investigate the novel function of Bazibushen (BZBS), a known anti-aging drug, in improving silica-induced lung fibrosis. We first confirmed the accumulation of senescent fibroblasts in the fibrotic regions of silicotic lungs. In both young (6-8 weeks) and aged (12 months) silicotic mice, BZBS exhibited anti-fibrosis and anti-senescence effects. Results of in vitro experiments showed the ability of BZBS to block the expression of p21, fibrotic markers, and senescence-associated secretory phenotype factors. Furthermore, BZBS was observed to attenuate mitochondrial dysfunction in senescent fibroblasts through FOXO1/PINK1/Parkin signaling. Collectively, these results indicated BZBS as a potential anti-fibrosis agent, which exerted its role through maintaining mitochondrial homeostasis in senescent fibroblasts.
    Keywords:  Bazibushen; Cellular senescence; Fibroblasts; Mitochondrial homeostasis; Silicosis
    DOI:  https://doi.org/10.1016/j.phymed.2025.156714
  12. Int J Nanomedicine. 2025 ;20 4051-4067
       Background: Skin aging is the primary external manifestation of human aging, and long-term exposure to ultraviolet radiation is the leading cause of photoaging, which can lead to actinic keratosis and skin cancer in severe cases. Traditional treatments may pose safety risks and cause side effects. As an emerging research direction, plant-derived exosome-like nanoparticles (PDNPs) show promise in combating aging. Aloe vera, known for its natural active ingredients that benefit the skin, aloe-derived exosome-like nanoparticles (ADNPs) have not yet been studied for their potential in delaying skin aging.
    Methods: In this study, nanoparticles were isolated from two different sites, aloe vera gel and aloe vera rind (gADNPs and rADNPs), and characterized by TEM, SEM, AFM, NTA and BCA. The effects were evaluated by constructing in vitro and in vivo models and using RT-qPCR, immunofluorescence, and histopathological analysis.
    Results: The results first revealed the exceptional anti-aging effects of ADNPs. We found that ADNPs promoted the nuclear translocation of Nrf2, alleviated oxidative stress and DNA damage induced by UV exposure, and inhibited the elevation of β-gal and SASP. In vivo, ADNPs reduced MDA and SOD levels in mouse skin tissue and delayed skin photoaging. Moreover, safety assessments confirmed the excellent biocompatibility of ADNPs.
    Conclusion: ADNPs delay skin photoaging through the Nrf2/ARE pathway, holding potential clinical application value, and may provide new therapeutic strategies for future medical cosmetology and skin disease prevention.
    Keywords:  aloe vera; anti-aging; antioxidants; cellular senescence; nanoparticles; skin photoaging
    DOI:  https://doi.org/10.2147/IJN.S510352
  13. Drug Target Insights. 2025 Jan-Dec;19:19 18-30
       Background: Withania somnifera is among the most widely prescribed medicinal plants in traditional Indian medicine. Hydroalcoholic extract of the roots of this plant was investigated for its effects on the overall health and lifespan of the model worm Caenorhabditis elegans.
    Methods: The extract's effect on worm lifespan and fertility was observed microscopically. Worm motility was quantified through an automated worm tracker. The metabolic activity of the worms was captured using the Alamar Blue® assay. Differential gene expression in extract-treated worms was revealed through a whole transcriptome approach.
    Results: Extract-exposed gnotobiotic worms, in the absence of any bacterial food, registered longer lifespan, higher fertility, better motility, and metabolic activity. Whole transcriptome analysis of the extract-treated worms revealed the differential expression of the genes associated with lifespan extension, eggshell assembly and integrity, progeny formation, yolk lipoproteins, collagen synthesis, cuticle molting, etc. This extract seems to exert its beneficial effect on C. elegans partly by triggering the remodeling of the developmentally programmed apical extracellular matrix (aECM). Differential expression of certain important genes (cpg-2, cpg-3, sqt-1, dpy-4, dpy-13, and col -17) was confirmed through PCR assay too. Some of the differently expressed genes (gfat-2, unc-68, dpy-4, dpy -13, col-109, col-169, and rmd-1) in worms experiencing pro-health effect of the extract were found through co-occurrence analysis to have their homologous counterpart in humans.
    Conclusions: Our results validate the suitability of W. somnifera extract as a nutraceutical for healthy aging.
    Keywords:  Caenorhabditis elegans; Fertility; Healthspan; Healthy aging; Longevity; Network analysis; Nutraceutical; Withania somnifera root; Worm transcriptome
    DOI:  https://doi.org/10.33393/dti.2025.3368
  14. Stem Cell Res Ther. 2025 Apr 06. 16(1): 167
      Neurodegenerative diseases including Alzheimer's and Parkinson's disease are age-related disorders which severely impact quality of life and impose significant societal burdens. Cellular senescence is a critical factor in these disorders, contributing to their onset and progression by promoting permanent cell cycle arrest and reducing cellular function, affecting various types of cells in brain. Recent advancements in regenerative medicine have highlighted "R3" strategies-rejuvenation, regeneration, and replacement-as promising therapeutic approaches for neurodegeneration. This review aims to critically analyze the role of cellular senescence in neurodegenerative diseases and organizes therapeutic approaches within the R3 regenerative medicine paradigm. Specifically, we examine stem cell therapy, direct lineage reprogramming, and partial reprogramming in the context of R3, emphasizing how these interventions mitigate cellular senescence and counteracting aging-related neurodegeneration. Ultimately, this review seeks to provide insights into the complex interplay between cellular senescence and neurodegeneration while highlighting the promise of cell-based regenerative strategies to address these debilitating conditions.
    Keywords:  Cell-based therapy; Neurodegenerative diseases; Rejuvenation; Reprogramming; Senescence
    DOI:  https://doi.org/10.1186/s13287-025-04285-7
  15. Biomol Biomed. 2025 Apr 01.
      Platelet factor 4 (PF4), a platelet-derived chemokine found in the blood, has been identified as a critical factor in modulating the rejuvenation of the aged brain. Increasing evidence suggests that PF4 secretion is a prerequisite for the cognitive benefits associated with young blood transfusion, the longevity factor klotho, and exercise. Systemic administration of exogenous PF4 has been shown to reduce circulating pro-aging immune factors and restore peripheral immune function in the aged brain by mitigating age-related hippocampal neuroinflammation, promoting molecular changes in synaptic plasticity, and improving cognitive function in aged mice. Clinically, reduced serum PF4 levels have been significantly associated with cognitive decline and core pathological biomarkers in Alzheimer's disease. Mechanistically, the chemokine receptor CXCR3 partially mediates the cellular, molecular, and cognitive benefits of systemic PF4 administration in the aged brain. However, several critical questions remain, including the potential role of PF4 in blood-brain communication, its interaction with neurotransmitters and neuropharmacological processes, and how these findings might be translated into clinical practice. Further detailed studies are needed to validate and expand upon these insights for therapeutic application.
    DOI:  https://doi.org/10.17305/bb.2025.11960
  16. Aging Biol. 2024 Feb 20. 1(1): 20240022
      Despite immense potential as anti-aging interventions, applications of current senolytics are limited due to low sensitivity and specificity. We demonstrate the specific loss of complex I-linked coupled respiration and the inability to maintain mitochondrial membrane potential upon respiratory stimulation as a specific vulnerability of senescent cells. Further decreasing the mitochondrial membrane potential of senescent cells with a mitochondrial uncoupler synergistically enhances the in vitro senolytic efficacy of BH3 mimetic drugs, including Navitoclax, by up to two orders of magnitude, whereas non-senescent cells remain unaffected. Moreover, a short-term intervention combining the mitochondrial uncoupler BAM15 with Navitoclax at a dose two orders of magnitude lower than typically used rescues radiation-induced premature aging in an in vivo mouse model, as demonstrated by reduced frailty and improved cognitive function for at least eight months. Our study shows compromised mitochondrial functional capacity is a senescence-specific vulnerability that can be targeted by mild uncoupling in vitro and in vivo.
    DOI:  https://doi.org/10.59368/agingbio.20240022
  17. J Mol Cell Cardiol. 2025 Apr 08. pii: S0022-2828(25)00063-X. [Epub ahead of print]
      Endothelial aging is an independent risk factor of cardiovascular diseases, and this study aims to explore the mechanism of endothelial aging. We first applied two animal aging models and two cellular aging models to observe the characteristics of senescent endothelium at the morphological, functional, and molecular levels. It was confirmed that the aging of endothelial cells was accompanied by activation of Nod like receptor protein 3 (NLRP3) inflammasome pathway, reduced the levels of hydrogen sulfide (H2S) and sirtuin2 (SIRT2) activity. Endothelial specific knockout of cystathionine-γ-lyase (CSE) led to premature aging of blood vessels, and excessive activation of the SIRT2/NLRP3 inflammasome. Finally, H2S supplementation improved vascular and endothelial cell function, normalized inflammatory cytokine levels, and thereby reversed endothelial aging through SIRT2/NLRP3 mediated pathway. In this study, we found that the decrease in SIRT2 activity in aging endothelial cells increased the level of NLRP3 inflammasome and H2S inhibited inflammation to improve endothelial aging through the SIRT2/NLRP3 pathway. This provided H2S could be a new target for improving endothelial aging, and offered new strategies for defending human aging.
    Keywords:  Endothelial senescence; Hydrogen sulfide; Inflammation; NLRP3; Sirtuin2
    DOI:  https://doi.org/10.1016/j.yjmcc.2025.04.005
  18. mSystems. 2025 Apr 08. e0166524
      Disruption of aryl hydrocarbon receptor (AhR) signaling and aberrant tryptophan metabolism have been shown to be highly associated with aging and age-related disorders. However, the underlying molecular mechanisms by which the AhR-mediated signaling pathway contributes to the aging process remain largely unknown. In this study, we find that aged Drosophila exhibits markedly reduced tryptophan metabolism leading to impaired AhR ligands, especially indole acetic acid (IAA), compared with their young controls. Supplementation with IAA, produced from Lactobacillus spp., dose-dependently extends the lifespan of Drosophila and improves healthy aging with resistance to starvation and oxidative stress. Mechanistically, activation of AhR by IAA markedly enhances Sirt2 activity by binding to its promoter, thereby inhibiting downstream TOR signaling and related fatty acid and amino acid metabolism. Both Ahr and Sirt2 mutant flies with IAA supplementation display a negligible lifespan extension, suggesting that AhR-mediated Sirt2 signaling contributes to lifespan extension in flies upon IAA supplementation. From the perspective of host metabolism, IAA supplementation significantly increases unsaturated fatty acids (UFAs) in aged flies, which are regarded to be beneficial for healthy status. These findings provide new insights into the physiological functions of AhR involved in the aging process by mediating Sirt2 signaling.
    IMPORTANCE: Disruption of aryl hydrocarbon receptor (AhR) signaling and aberrant tryptophan metabolism contribute to aging and age-related disorders, but the underlying molecular mechanisms are largely unknown. Using multiomics analyses combined with biochemical assays, this study reveals that AhR activation by indole acetic acid (IAA) effectively extends the lifespan accompanied by improved healthy aging in Drosophila via the AhR-Sirt2 pathway.
    Keywords:  Aging; AhR; Drosophila; Sirt2
    DOI:  https://doi.org/10.1128/msystems.01665-24
  19. Eur J Pharm Sci. 2025 Apr 09. pii: S0928-0987(25)00097-1. [Epub ahead of print] 107098
      Biological ageing is a time-dependent process that has implications for health and disease. Cellular senescence is a key driver in ageing and age-related diseases. Senotherapeutic agents have been shown to slow biological ageing by eliminating senescent mammalian cells. Given the increasing awareness of the gut microbiome in regulating human health, this study aimed to investigate the effects of senotherapeutic agents as pharmacological interventions on the human gut microbiota. In this study, the bidirectional effects of four senotherapeutic agents, quercetin, fisetin, dasatinib, and sirolimus, with the gut microbiota sourced from healthy human donors were investigated. The results revealed that quercetin was completely biotransformed by the gut microbiota within six hours, while dasatinib was the most stable of the four compounds. Additionally, metagenomic analysis confirmed that all four compounds increased the abundance of bacterial species associated with healthy ageing (e.g., Bacteroides fragilis, Bifidobacterium longum, and Veillonella parvula), and decreased the abundance of pathogenic bacteria primarily associated with age-related diseases (e.g., Enterococcus faecalis and Streptococcus spp.). The findings from this study provide a comprehensive understanding of the pharmacobiomics of senotherapeutic interventions, highlighting the potential of microbiome-targeted senolytics in promoting healthy ageing.
    Keywords:  Anti-ageing; Dasatinib; Fisetin; Flavonoids; Gut bacteria; Quercetin; Senolytics; Senotherapeutics; Sirolimus; senescent cell
    DOI:  https://doi.org/10.1016/j.ejps.2025.107098
  20. Front Pharmacol. 2025 ;16 1526107
      The incidence of intervertebral disc degeneration (IDD) is increasing year by year, while the age of onset of IDD is decreasing year by year. For the individuals affected by IDD, an alternative treatment to surgery is required. IDD is thought to be related to nucleus pulposus (NP) cell senescence and inflammation. Therefore, inhibition of NP cell inflammation and senescence may counteract IDD. We screened 20 small-molecule drugs to compare their anti-inflammatory effects, and finally selected homoplantaginin (HPG) as a treatment regimen. HPG is an extract of Salvia miltiorrhiza with anti-inflammatory properties. The objective of this research was to investigate if HPG could have a therapeutic effect on IDD through its anti-inflammatory or anti-aging effects. We identified the appropriate concentration of HPG in primary NP cell cultures and demonstrated that it inhibited inflammatory pathway activation and reduced the senescence phenotype of NP cells in vitro. And in vivo, the therapeutic effect of HPG on caudal disc degeneration was confirmed consistently. In conclusion, our findings suggest that HPG can alleviate the degeneration in the pathogenesis of IDD and that it has a potential effect in the treatment of IDD.
    Keywords:  homoplantaginin; inflammation; intervertebral disc degeneration; nucleus pulposus cell; senescence
    DOI:  https://doi.org/10.3389/fphar.2025.1526107
  21. J Craniofac Surg. 2025 Apr 07.
      The aim of this study was to analyze the novella "The Last Revolt (La dernière révolte)" through the lens of anti-aging and plastic surgery. Bernard Werber's "The Last Revolt" is a dystopian novella that portrays a future where society imprisons elderly population in specialized centers. The story focuses on Fred and his group of rebels, the White Foxes, who challenge this oppressive system. It examines themes of gerontophobia, societal rejection of aging, and the fight for dignity and freedom. "Foxes then disguised themselves as 'young people', dyed their hair and provided themselves with false papers presenting themselves as children 'taken with remorse', who had come at the end of the period of reflection to recover their ancestors. Little by little, faced with such a resurgence of repentants, the authorities became intrigued and this sowed doubt. From then on, anyone presenting themselves to take back their parents was required to first show their hands. These always betray the age of their owner." Foxes underscores society's obsession with youthfulness as a key aspect of identity and value. Their subsequent failure, attributed to the appearance of wrinkles on their hands, highlights the pervasive societal fixation on aging signs. This situation suggests a world where age-related characteristics are inescapable markers of exclusion. It suggests a burgeoning market for hand rejuvenation techniques, such as fillers or laser treatments, which are gaining popularity. It underscores the rising demand for aesthetic procedures targeting areas of the body that are frequently ignored yet can still reveal one's age.
    Keywords:  Aging; literature; modern; plastic; social norms; surgery
    DOI:  https://doi.org/10.1097/SCS.0000000000011323
  22. J Drugs Dermatol. 2025 Apr 01. 24(4): 366-370
      The Transient Receptor Potential Vanilloid 1 (TRPV1) protein, originally recognized for its role in modulating peripheral sensory neurons and transmitting pain and itch signals, has been increasingly implicated in various dermatological processes. TRPV1 is widely expressed in skin cells, including keratinocytes, fibroblasts, and mast cells, making it a promising target for treating inflammatory skin diseases, skin sensitivity, wound healing, and aging. Activation of TRPV1 by environmental stressors, such as heat and ultraviolet (UV) exposure, induces pro-inflammatory responses and contributes to the degradation of collagen, exacerbating conditions like chronic itch, atopic dermatitis, and dermatoheliosis. This study evaluates the effectiveness of topical formulations containing a sea anemone biomimetic peptide (SABMP), a TRPV1 antagonist, in improving skin texture, elasticity, hydration, and rejuvenation. Clinical trials involved participants with self-perceived sensitive skin, who applied the test formulations for 4 weeks. Results demonstrated significant improvements in skin texture, elasticity, and reductions in erythema and fine lines, highlighting the potential of TRPV1-targeting peptides as an alternative to conventional treatments like retinoids and Vitamin C, particularly for individuals with sensitive skin. The study underscores the clinical utility of TRPV1 antagonism in skin care, offering a novel approach to managing skin sensitivity and aging. These findings suggest that TRPV1-targeting peptides can provide a safe and effective treatment modality for enhancing skin quality and addressing conditions such as atopic dermatitis, rosacea, and acne. J Drugs Dermatol. 2025;24(4):366-371. doi:10.36849/JDD.8680.
    DOI:  https://doi.org/10.36849/JDD.8680
  23. Front Pharmacol. 2025 ;16 1498358
       Introduction: Sheep placenta extract (SPE) is a representative traditional medicinal substance that exhibits multiple experimentally validated physiological properties, including anti-aging effects, wound healing acceleration, antioxidant activity, and anti-inflammatory mechanisms. However, the mechanism by which SPE influences the delay of aging is still not yet clear.
    Methods: Exploring the effects of sheep placenta extract on D-gal induced senescence in a mouse model of aging by macrogenomics and metabolomics.
    Results: In the serum of aging mice treated with SPE, the levels of antioxidant function such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were notably higher compared to those in the blank group, whereas malondialdehyde (MDA) levels decreased. We revealed that SPE alleviated the changes in gut microbiota caused by aging in mice, with a significant decrease in the Firmicutes/Bacteroidetes (F/B) ratio in the gut. Furthermore, Akkermansia muciniphila (A. muciniphila), which is known for its regulating immune response and potential anti-aging effects, showed a significant increase of 1177.94%. The analysis of UHPLC-QE-MS combined with orthogonal partial least squares discriminant analysis (OPLS-DA) screening of differential metabolites in mouse serum metabolic profiles revealed a significant upregulation of cis-5,8,11,14,17-eicosapentaenoic acid (EPA) and triptolide in serum metabolites, following SPE treatment, which are commonly believed to have immunosuppressive, anti-inflammatory, anti-proliferative, and anti-tumor effects.
    Discussion: The role of SPE in ameliorating aging may be associated with the increased abundance of A. muciniphila in the gut microbiota and the accumulation of two metabolites, EPA and triptolide, in the serum.
    Keywords:  D-galactose; anti-aging; antioxidant; gut microbiota; sheep placenta extract
    DOI:  https://doi.org/10.3389/fphar.2025.1498358
  24. Arch Pharm Res. 2025 Apr 10.
      Antioxidants are organic molecules that scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS), thereby maintaining cellular redox balance in living organisms. The human body synthesizes endogenous antioxidants, whereas humans obtain exogenous antioxidants from other organisms such as plants, animals, fungi, and bacteria. This review primarily focuses on the antioxidant potential of natural metabolites and extracts from five major bacterial phyla, including the well-studied Actinobacteria and Cyanobacteria, as well as less-studied Bacteroides, Firmicutes, and Proteobacteria. The literature survey revealed that the metabolites and the extracts with antioxidant activity can be obtained from bacterial cells and their culture supernatants. The metabolites with antioxidant activity include pigments, phycobiliproteins, polysaccharides, mycosporins-like amino acids, peptides, phenolic compounds, and alkaloids. Both metabolites and extracts demonstrate in vitro antioxidant capacity through radical-scavenging, metal-reducing, and metal-chelating activity assays. In in vivo models, they can scavenge ROS and RNS directly and/or indirectly eliminate them by enhancing the activities of antioxidant enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase. Due to their antioxidant activities, they may find applications in the cosmetic industry as anti-aging agents for the skin and in medicine as drugs or supplements for combating oxidative stress-related disorders, such as neurodegenerative diseases and diabetes. The literature survey also elucidated that some metabolites and extracts with antioxidant activity also exhibited strong antimicrobial properties. Therefore, we consider that they may have future applications in the treatment of infectious diseases, the preparation of pathogen-free healthy foods, and the extension of food shelf life.
    Keywords:   Actinobacteria ; Cyanobacteria ; Proteobacteria ; Exogenous antioxidants; Natural metabolites; Oxidative stress
    DOI:  https://doi.org/10.1007/s12272-025-01541-5
  25. Res Sq. 2025 Mar 26. pii: rs.3.rs-6081213. [Epub ahead of print]
      Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron degeneration in the primary motor cortex (PMC) and spinal cord. Aging is a key factor in ALS onset and progression, with evidence suggesting that biological aging-a process involving cellular decline- far outpaces chronological aging in ALS. This promotes senescent cell accumulation-marked by irreversible cell-cycle arrest, impaired apoptosis, and chronic inflammation-disrupting tissue homeostasis and impairing neuronal support functions. Thus, targeting senescence presents a novel therapeutic strategy for ALS. Here, we investigated the senolytic combination Dasatinib and Quercetin (D&Q) in TDP-43 Q331K ALS mice. D&Q improved neuromuscular function and reduced plasma neurofilament light chain, a biomarker of axonal damage. The most pronounced improvement was the improved cortical excitability, accompanied by reductions in senescence and TDP-43 in the PMC. These findings highlight the potential of senolytics to mitigate ALS-related dysfunction, supporting their viability as a therapeutic strategy. *Jose A. Viteriab, Nathan R. Kerrab, and Charles D. Brennana are co-first authors.
    DOI:  https://doi.org/10.21203/rs.3.rs-6081213/v1
  26. Cells. 2025 Mar 27. pii: 499. [Epub ahead of print]14(7):
      Cellular senescence is an irreversible state of cell cycle arrest. Senescent cells (SCs) accumulate in the body with age and secrete harmful substances known as the senescence-associated secretory phenotype (SASP), causing chronic inflammation; at the same time, chronic inflammation leads to a decrease in immune system function, known as immunosenescence, which further accelerates the aging process. Cellular senescence and immunosenescence are closely related to a variety of chronic diseases, including cardiovascular diseases, metabolic disorders, autoimmune diseases, and neurodegenerative diseases. Studying the mechanisms of cellular senescence and immunosenescence and developing targeted interventions are crucial for improving the immune function and quality of life of elderly people. Here, we review a series of recent studies focusing on the molecular mechanisms of cellular senescence and immunosenescence, the regulation of aging by the immune system, and the latest advances in basic and clinical research on senolytics. We summarize the cellular and animal models related to aging research, as well as the mechanisms, strategies, and future directions of aging interventions from an immunological perspective, with the hope of laying the foundation for developing novel and practical anti-aging therapies.
    Keywords:  SASP; aging; cellular senescence; immunosenescence; senolytic
    DOI:  https://doi.org/10.3390/cells14070499
  27. Dermatol Reports. 2025 Apr 11.
      Skin aging is characterized by loss of elasticity, wrinkles, and textural changes. Treatments range from non-invasive options, such as alpha-hydroxy acids and retinoic acid, to invasive procedures like chemical peels and laser therapies. Plasma radiofrequency (PRF) offers a minimally invasive solution with a favorable balance of efficacy and tolerability. This study assessed the clinical and microscopic outcomes of combining PRF ablation with a galenic cream containing 5% resorcinol in Nourivan™ Antiox for facial skin aging. Forty-one patients with visible signs of aging underwent a single PRF session followed by weekly applications of a 5% resorcinol cream for six weeks. Outcomes were evaluated using digital photography and line-field confocal optical coherence tomography (LC-OCT) at baseline, three months, and six months. Primary endpoints included wrinkle reduction and texture improvement; secondary endpoints included adverse effects and patient satisfaction. At six months, 92% of patients showed significant wrinkle reduction and improved collagen organization in LC-OCT images. Skin texture improvements were reported by 85% of patients. Adverse effects, such as mild erythema and peeling, were transient and resolved without discontinuation. PRF ablation combined with 5% resorcinol cream is an effective and well-tolerated treatment for facial skin aging, offering significant improvements in skin texture and appearance. Further research is needed to confirm these findings and explore long-term effects.
    DOI:  https://doi.org/10.4081/dr.2025.10342
  28. J Cosmet Dermatol. 2025 Apr;24(4): e70169
       OBJECTIVE: As the body's largest organ, the skin plays a crucial role in defending against external stressors. Skin characteristics change with age, decreasing skin barrier integrity and compromising skin and body health. This study aimed to investigate the potential of a topical formulation containing OS-01 (a.k.a. Peptide 14), a senotherapeutic peptide, to counteract age-related skin changes and their systemic consequences.
    METHODS: A randomized, double-blinded clinical trial involving 60 female volunteers aged 60-90 was conducted over 12 weeks. Participants received either an OS-01 topical formulation or a commercially available moisturizer control formulation. Skin parameters, subjective perceptions, and circulating cytokine levels were assessed. Skin instrumental analysis included transepidermal water loss (TEWL), skin hydration, and pH measurements.
    RESULTS: Participants treated with the OS-01 topical formulation displayed significantly improved skin barrier function and hydration compared to the control group. Participant perceptions aligned with objective findings: after 12 weeks, 70% of participants in the OS-01 group noticed an improvement in general skin appearance versus 42% for the control group. The systemic levels of proinflammatory cytokines tended to normalize, with a significant decrease in IL-8 in the blood analysis of participants from the OS-01 group. On the other hand, the control group demonstrated an increase in a few circulating cytokines, particularly TNF-ɑ and IFN-γ. Moreover, GlycanAge analysis measuring participants' biological age suggested the slowing of systemic aging in the group treated with the OS-01 topical formulation.
    CONCLUSION: The study suggests that the OS-01 formulation can impact skin health by improving the skin barrier function, potentially influencing systemic inflammation and biological age. In conclusion, the study supports that targeting skin health may contribute to better longevity outcomes, underscoring the skin's pivotal role in systemic aging and supporting an integrated approach to health management.
    Keywords:  clinical trial; inflammation; senescence; skin aging; skin barrier function
    DOI:  https://doi.org/10.1111/jocd.70169
  29. MicroPubl Biol. 2025 ;2025
      Neopterin, a byproduct of tetrahydrobiopterin synthesis, is commonly used as a biomarker for immune system activation. In addition to its role in immune responses, neopterin levels are known to increase with age. Its impact on longevity, however, remains unclear. Here, we demonstrate that neopterin supplementation extends lifespan in Caenorhabditis elegans . Additionally, neopterin shows moderate activation of the mitochondrial unfolded protein response (UPR mt ), and that the neopterin-mediated lifespan extension is dependent on ATFS-1 , the primary transcription factor regulating UPR mt . These findings highlight the need for further investigation into the biological functions and health-promoting effects of neopterin.
    DOI:  https://doi.org/10.17912/micropub.biology.001543
  30. J Enzyme Inhib Med Chem. 2025 Dec;40(1): 2488821
      Skin ageing is a complex physiological process primarily characterised by the deepening of wrinkles and the sagging of the skin. Collagen is essential for maintaining skin elasticity and firmness. As skin ages, it experiences structural and functional changes in collagen, including a decrease in collagen synthesis and an increase in collagen hydrolysis. Thus, promoting collagen synthesis represents a practical strategy for mitigating skin ageing. This review systematically described the functions, classifications and biosynthesis process of collagen, as well as its role in skin ageing. Additionally, the major signalling pathways and targets associated with collagen synthesis were also discussed. More importantly, the review provided a detailed summary of natural products with collagen synthesis-promoting effects and highlighted small molecule compounds with potential anti-ageing activity, especially PPARδ agonists. The relevant content offers potential targets and lead compounds for the development of anti-skin ageing therapies.
    Keywords:  Collagen; PPARδ agonist; drug discovery; natural product; skin ageing
    DOI:  https://doi.org/10.1080/14756366.2025.2488821
  31. Clin Exp Hypertens. 2025 Dec;47(1): 2487891
      Aging-related diseases, which are associated with the senescence of endothelial progenitor cells (EPCs), are consistently accompanied by elevated levels of circulating trimethylamine-N-oxide (TMAO), a marker predictive of poor prognosis. Lycopene (Lyc) deficiency has been demonstrated to be linked to these age-related diseases. The AMPK/SIRT1 pathway plays a pivotal role in cellular senescence. In this study, we hypothesize that lycopene could mitigate TMAO-induced EPCs senescence, with involvement of the AMPK/SIRT1 pathway. EPCs were subjected to treatment with TMAO, Lyc, small interfering RNA targeting AMP-activated protein kinase (siAMPK), or sirtin-1 (siSIRT1). The biological functions of EPCs were evaluated through, CCK-8, transwell and tube formation assays, while their senescence was assessed via SA-β-gal activity assay and Western blotting. ROS generation was measured using dichlorodihydrofluorescein diacetate staining. TMAO-induced suppression of EPCs' functionality was alleviated by Lyc, but this effect was reversed by siAMPK and siSIRT1. TMAO increased SA-β-gal-positive cell number and ROS production, while reducing the expression of AMPK and SIRT1. These effects were attenuated by Lyc. However, the protective effects were diminished by siAMPK and siSIRT1. In conclusion, Lyc ameliorates TMAO-induced EPCs senescence through the AMPK/SIRT1 pathway.
    Keywords:  AMPK/SIRT1 pathway; Lycopene; endothelial progenitor cells; senescence; trimethylamine-N-oxide
    DOI:  https://doi.org/10.1080/10641963.2025.2487891
  32. Front Physiol. 2025 ;16 1565270
      Cognition broadly refers to the ability to perform mental processes such as learning and memory, attention, emotional awareness, and higher-order thinking. Cognitive deficits can result from the normal aging process or other factors such as disease progression or injury. While the exact etiology is not fully understood, emerging evidence suggests that enhanced inflammatory and oxidative stress processes during aging can dramatically decrease cognitive function in older adults, as well as contribute to the onset and progression of neurocognitive disorders. Current treatments for neurocognitive disorders have limited efficacy and typically focus on symptom attenuation rather than targeting intrinsic pathophysiology. With the rising aging population, there is a critical need to identify novel treatment approaches that target the underlying inflammatory and oxidative mechanisms contributing to neurocognitive disorders. In this regard, the renin-angiotensin system (RAS) may provide an ideal target, as this hormonal system has been implicated in the regulation of inflammatory and oxidative responses to impact cognitive functions. While most research to date has focused on the deleterious role of angiotensin (Ang) II pathways in age-related cognitive decline and neurocognitive disorders, more recent evidence has examined the potential for targeting Ang-(1-7), a protective hormone of the RAS, to counteract these effects. This review highlights emerging evidence showing that activation of Ang-(1-7) pathways reduces inflammation and oxidative stress and may provide a novel target to improve cognitive function and elicit neuroprotection, in the context of both aging and neurocognitive disorders.
    Keywords:  aging; brain; cognition; inflammation; renin-angiotensin system
    DOI:  https://doi.org/10.3389/fphys.2025.1565270
  33. Biomater Res. 2025 ;29 0180
      UVR-related skin damage is common in daily life. Excessive sunlight exposure, particularly in response to ultraviolet B (UVB) radiation, can have adverse effects on the skin and can even induce photosensitive skin diseases and skin malignancies. UVB exposure leads to the production of reactive oxygen species (ROS) in the skin, resulting in cell damage and inflammation. Furthermore, it directly inhibits the synthesis of collagen in skin fibroblasts, contributing to collagen degradation and subsequently causing skin aging, wrinkles, and erythema. To address this issue, our study introduces a biomaterial-based treatment plan for repairing UVB-induced photodamaged skin. We designed a sodium hyaluronate microneedle patch containing a hardystonite bioceramic (ZnCS/MN) with anti-ROS/inflammation/collagen degradation functions to deliver bioactive Zn2+ and SiO3 2- ions in situ to photodamaged skin areas. In addition, the cytological mechanism of ZnCS action was explored to explore the possibilities of its application in more areas. This study reveals the therapeutic potential of ZnCS for a variety of negative effects caused by photodamage. Owing to its advantages in preparation, storage, and transportation, ZnCS/MN has shown promise for clinical application in treating photodamaging.
    DOI:  https://doi.org/10.34133/bmr.0180
  34. J Cosmet Dermatol. 2025 Apr;24(4): e70117
       INTRODUCTION: Hyaluronic acid (HA)-based formulations could have remarkable efficacy in treating a wide range of skin defects, including skin aging. The purpose of the study was the evaluation of the clinical safety and efficacy of a high and low molecular weight HA hybrid complex injection for skin rejuvenation.
    METHOD: In this single-arm, before-and-after clinical study, 20 subjects with wrinkled, dry, or rough skin were enrolled. They received two treatment sessions, each of 2 mL of stabilized high- and low-molecular-weight HA through intradermal injections in five bioaesthetic points with an interval of 4 weeks. Efficacy assessment measures included biophysical and sonographic parameters and the Global Aesthetic Improvement Scale (GAIS) score. Pain assessment, safety profile, and subject satisfaction were also reported.
    RESULTS: A significant improvement in skin firmness was demonstrated in both follow-up visits. The Transepidermal water loss (TEWL) and the dermis ecodensity improved significantly in the first follow-up visit. A statistically significant increase in the dermis thickness was seen in the second follow-up visit. The median GAIS score indicated an average improvement of 51%-75%. The median overall satisfaction score was 7 and 6 in the first and second follow-up visits. No important side effects were observed. The average pain VAS score was 2 out of 10.
    CONCLUSION: This new HA-based formulation is a safe and efficient treatment option to restore the vitality and turgidity of the skin.
    TRIAL REGISTRATION: ClinicalTrials.gov identifier: IRCT20150101020514N17 with ethics code IR.TUMS.TIPS.REC.1401.083.
    Keywords:  TEWL; dermis density; dermis thickness; elasticity; high and low molecular weight; hyaluronic acid; hydration
    DOI:  https://doi.org/10.1111/jocd.70117
  35. J Biol Chem. 2025 Apr 09. pii: S0021-9258(25)00349-7. [Epub ahead of print] 108500
      The complement system plays an important role in bone growth during physiological development and skeletal homeostasis. However, the specific impact of the complement C3a receptor (C3aR) on age-related bone loss remains unclear. In this study, we found that C3aR expression increased with age and was the same as that of the senescent molecules p53, p21 and p16 in control mice. Knockdown of C3aR reduced the expression of senescence markers and significantly ameliorated bone senescence. Notably, C3aR knockdown in mice effectively reversed age-induced bone loss, which was characterized by an increase in the number of osteoblasts and a decrease in the number of osteoclasts. In an in vitro model of D-gal-induced senescence, increased expression of C3aR correlated with increased expression of senescence markers such as p53, p21, and p16. Treatment with a C3aR antagonist (JR14a) successfully attenuated the expression of these markers of cellular senescence and reduced the proportion of late apoptotic cells. Mechanistically, JR14a treatment mitigated D-gal-mediated inhibition of osteoblastic differentiation in preosteoblasts through activation of the YAP1/β-catenin signalling pathway. In D-gal-induced aging mouse model, treatment with JR14a ameliorates bone microarchitecture and bone loss. In summary, these studies revealed a role for C3aR in regulating bone homeostasis, suggesting that targeting C3aR may be a promising therapeutic strategy for the treatment of age-related osteoporosis.
    Keywords:  Age-related bone loss; Bone homeostasis; C3aR; JR14a
    DOI:  https://doi.org/10.1016/j.jbc.2025.108500
  36. J Nanobiotechnology. 2025 Apr 10. 23(1): 287
      This study investigates how miR-146a-5p, found in adipose tissue-derived small extracellular vesicles (sEV), influences mitochondrial autophagy and its impact on delaying skeletal muscle aging through the targeting of Fbx32. The findings highlight miR-146a-5p as crucial in skeletal muscle development and aging, influencing autophagy, apoptosis, differentiation, and proliferation, collectively impacting muscle atrophy. In C2C12 cells, miR-146a-5p mimics decreased apoptosis, autophagy, and reactive oxygen species (ROS) levels, while enhancing ATP production; conversely, miR-146a-5p inhibitors had the opposite effects. Furthermore, miR-146a-5p-enriched sEV from adipose tissue alleviated skeletal muscle atrophy in aged mice and promoted muscle fiber growth and repair by regulating mitochondrial autophagy and apoptosis. Mechanistically, miR-146a-5p modulated mitochondrial autophagy in myoblasts by targeting Fbx32 and impacting the FoxO3 signaling pathway. This led to a notable decrease in apoptosis-related gene expression, reduced ROS production, and elevated ATP levels. In conclusion, miR-146a-5p derived from WAT-sEV modulates myoblast autophagy, apoptosis, ROS, and differentiation through the Fbx32/FoxO3 signaling axis. This work presents a novel molecular target and theoretical framework for delaying skeletal muscle aging and developing therapies for skeletal muscle-related disorders.
    Keywords:  Aging; Fbx32; Mitochondrial autophagy; miR-146a-5p; sEV
    DOI:  https://doi.org/10.1186/s12951-025-03367-1