bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2025–04–27
forty-one papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño



  1. Int J Biol Macromol. 2025 Apr 19. pii: S0141-8130(25)03872-3. [Epub ahead of print]310(Pt 3): 143320
      Natural polysaccharides, a class of biological macromolecules found in nature, have recently attracted considerable interest owing to their notable anti-aging capabilities. This article provides a comprehensive review of the intricate mechanisms through which natural polysaccharides combat aging, as well as their applications in addressing skin aging. Primarily, these polysaccharides manifest their anti-aging effects via diverse pathways, such as antioxidation, gut microbiota regulation, metabolic modulation, and immune system regulation. The anti-aging efficacy of natural polysaccharides is intrinsically linked to their structure-activity relationships, with critical determinants including molecular weight, monosaccharide composition, and chemical architecture. Polysaccharides with lower molecular weights typically demonstrate enhanced biological activity, whereas specific monosaccharide configurations and chemical modifications can markedly augment their anti-aging potential. The utilization of natural polysaccharides in skin aging holds significant promise, offering benefits such as anti-aging, wrinkle reduction, anti-glycation, and the facilitation of skin regeneration. In conclusion, this article synthesizes the advancements in research on natural polysaccharides within the anti-aging sector and forecasts future trajectories, to establish a robust foundation for the innovation of new polysaccharide-derived anti-aging formulations.
    Keywords:  Anti-aging; Natural polysaccharides; Structure-activity relationships
    DOI:  https://doi.org/10.1016/j.ijbiomac.2025.143320
  2. J Adv Res. 2025 Apr 22. pii: S2090-1232(25)00271-1. [Epub ahead of print]
       INTRODUCTION: Frailty is characterized by an increased vulnerability to disease and physical debilitation due to a decline in the body's capacity to maintain homeostasis during aging. Therefore, effective management of frailty is crucial for promoting health. Although the role of niclosamide (NIC), an autophagy promoter, has been studied for the treatment of cancer, infectious diseases, and metabolic disorders, no research has focused on its effects on aging.
    OBJECTIVES: In this study, we aimed to evaluate the effects of NIC on the aging process and assess its potential as a novel anti-aging therapeutic agent.
    METHODS: We evaluated the effects of NIC on frailty, physical function, and metabolic function using Caenorhabditis elegans (C. elegans) and aging mouse models. NIC effectiveness was assessed using behavioral experiments, histological analysis, and molecular biological analysis.
    RESULTS: We identified NIC as a compound that enhanced exercise capacity and metabolism, thereby alleviating frailty. Briefly, NIC extended the lifespan and improved frailty-related phenotypes in C. elegans, and effectively ameliorated frailty in aging mice, particularly in muscle aging. Additionally, NIC treatment suppressed the muscle atrophy-related ubiquitin-proteasome system induced by mammalian target of rapamycin complex 1 (mTORC1) hyperactivation, while enhancing autophagic flux, another aspect of proteostasis. Furthermore, mRNA-seq analysis revealed that NIC improved metabolism-related functions.
    CONCLUSION: Collectively, these findings suggest that NIC is a promising novel candidate for the prevention of frailty.
    Keywords:  Aging; Caenorhabditis elegans; Health span; Longevity; Sarcopenia; Skeletal muscle
    DOI:  https://doi.org/10.1016/j.jare.2025.04.027
  3. Mol Biol Rep. 2025 Apr 22. 52(1): 410
      Drug repurposing is the process of using currently approved drugs for a novel treatment or medical condition for which it was not previously indicated. Despite promising preclinical and clinical results, most of the newly designed senotherapeutic agents synthesized have limited clinical utility due to individual and organ-specific variations in aging phenotype and adverse side effects. All these limitations indicate that further clinical research is required to determine the effectiveness of repurposed senotherapeutic drug interventions, such as metformin, for age-related diseases. Metformin exerts diverse senotherapeutic effects on various aging tissues at different metabolic conditions. Although not exhibiting senolytic properties, metformin has effectively suppressed cellular senescence and senescence-associated secretory phenotype (SASP) in age-related diseases (ARDs). Targeting specific SASP-related signaling pathways with metformin may offer new therapeutic benefits to alleviate the detrimental effects of senescent cells accumulated in most common ARDs in the elderly. Metformin was also the first drug evaluated for its senescence-targeting effects in a large clinical trial named "Targeting Aging with Metformin (TAME)". In this review, we critically evaluate the literature to highlight senotherapeutic mechanisms in which metformin can be therapeutically repurposed for the prevention and treatment of ARDs.
    Keywords:  Age-related disorders; Cancer; Metformin; Senescence; Senoblocker; Senoreverser; Senotherapeutic; TAME
    DOI:  https://doi.org/10.1007/s11033-025-10524-0
  4. Front Pharmacol. 2025 ;16 1559584
      Introduction: Aging is associated with significant metabolic alterations that contribute to cellular senescence and age-related functional decline. As individuals age, an increased prevalence of oral diseases and a gradual decline in oral functions are observed. However, the metabolic shifts underlying oral mucosal aging remain unexplored. Methods: We initially conducted histological analyses on the tongues from young (4-week-old), adult (4-month-old) and old (20-month-old) C57BL/6 mice to identify age-related alterations in the tongue mucosa. Subsequently, metabolomics analysis was performed to characterize metabolic profiles of mouse tongues across these age groups and identify metabolic biomarkers of oral mucosal aging. Then we validate the anti-senescence effect of carnosine and investigate its underlying mechanisms using a tert-butyl hydroperoxide (tBHP)-induced cellular senescence model in vitro. Finally, metabolomics analyses of human saliva and blood were conducted to explore associations between carnosine levels and systemic aging. Results: Compared to young and adult mice, we observed epithelial atrophy and an accumulation of senescent cells in the tongue mucosa of old mice. After that, we found significant differences in the metabolic profiles among the young, adult, and old mouse tongues. Carnosine was identified as a potential biomarker of oral mucosal aging, as its levels declined significantly with age. Consistently, carnosine synthase 1 (CARNS1) activity decreased, and carnosinase 2 (CNDP2) activity increased with age in the tongue mucosa. Furthermore, carnosine protected oral epithelial cells from tBHP-induced cellular senescence by reducing oxidative stress, mitigating DNA damage, and downregulating Nrf2/HO-1 pathway. In humans, salivary and blood carnosine levels also declined with age and were significantly associated with age-related diseases. Discussion: Our findings reveal dynamic metabolic reprogramming during natural oral mucosal aging and highlight the dual role of carnosine as both an aging biomarker and a therapeutic target for combating age-related mucosal degeneration. These insights support the development of novel carnosine-based interventions to preserve oral mucosal function, prevent age-related oral diseases, and improve oral health in the aging population, thereby advancing healthy aging.
    Keywords:  aging; carnosine; metabolomics; oral mucosa; senescence
    DOI:  https://doi.org/10.3389/fphar.2025.1559584
  5. Chin Herb Med. 2025 Apr;17(2): 279-291
      Natural polyphenols are a group of components widely found in traditional Chinese medicines and have been demonstrated to delay or prevent the development of aging and age-related diseases in recent years. As far as we know, the studies of natural polyphenols in aging and aging-related diseases have never been extensively reviewed. In the present paper, we reviewed recent advances of natural polyphenols in aging and common age-related diseases and the current technological methods to improve the bioavailability of natural polyphenols. The results showed that natural polyphenols have the potential to prevent or treat aging and common age-related diseases through multiple mechanisms. Nanotechnology, structural modifications, and matrix processing could provide strong technical support for the development of natural polyphenols to prevent or treat aging and age-related diseases. In conclusion, natural polyphenols have important potential in the prevention and treatment of aging and age-related diseases.
    Keywords:  aging; cancer; cardiovascular disease; natural polyphenols; neurodegenerative diseases
    DOI:  https://doi.org/10.1016/j.chmed.2024.09.001
  6. Cells. 2025 Apr 21. pii: 619. [Epub ahead of print]14(8):
      A significant increase in life expectancy worldwide has resulted in a growing aging population, accompanied by a rise in aging-related diseases that pose substantial societal, economic, and medical challenges. This trend has prompted extensive efforts within many scientific and medical communities to develop and enhance therapies aimed at delaying aging processes, mitigating aging-related functional decline, and addressing aging-associated diseases to extend health span. Research in aging biology has focused on unraveling various biochemical and genetic pathways contributing to aging-related changes, including genomic instability, telomere shortening, and cellular senescence. The advent of induced pluripotent stem cells (iPSCs), derived through reprogramming human somatic cells, has revolutionized disease modeling and understanding in humans by addressing the limitations of conventional animal models and primary human cells. iPSCs offer significant advantages over other pluripotent stem cells, such as embryonic stem cells, as they can be obtained without the need for embryo destruction and are not restricted by the availability of healthy donors or patients. These attributes position iPSC technology as a promising avenue for modeling and deciphering mechanisms that underlie aging and associated diseases, as well as for studying drug effects. Moreover, iPSCs exhibit remarkable versatility in differentiating into diverse cell types, making them a promising tool for personalized regenerative therapies aimed at replacing aged or damaged cells with healthy, functional equivalents. This review explores the breadth of research in iPSC-based regenerative therapies and their potential applications in addressing a spectrum of aging-related conditions.
    Keywords:  aging-related diseases; cellular reprogramming; induced pluripotent stem cells; personalized therapies; regenerative medicine
    DOI:  https://doi.org/10.3390/cells14080619
  7. Adv Sci (Weinh). 2025 Apr 23. e2412950
      Cellular senescence is a cell fate triggered by stressful stimuli and displays a hypersecretory feature, the senescence-associated secretory phenotype (SASP). Senescent cell burden increases with aging and contributes to age-related organ dysfunction and multiple chronic disorders. In this study, a large scale screening of a natural product library for senotherapeutic candidates is performed. Apigenin, a dietary flavonoid previously reported with antioxidant and anti-inflammatory activities, exhibits capacity for targeting senescent cells as a senomorphic agent. This compound blocks the interactions between ATM/p38MAPK and HSPA8, preventing the transition of an acute stress-associated phenotype (ASAP) toward the SASP. Mechanistically, apigenin targets peroxiredoxin 6 (PRDX6), an intracellular redox-active molecule, suppressing the iPLA2 activity of PRDX6 and disrupting downstream reactions underlying SASP development. Apigenin reduces the severity of cancer cell malignancy promoted by senescent stromal cells in culture, while restraining chemoresistance when combined with chemotherapy in anticancer regimens. In preclinical trials, apigenin improves the physical function of animals with a premature aging-like state, alleviating physical frailty and cognitive impairment. Together, the study demonstrates the feasibility of exploiting a natural compound with senomorphic capacity to achieve geroprotective effects by modulating the SASP, thus providing a baseline for future exploration of natural agents for alleviating age-related conditions.
    Keywords:  SASP; aging; apigenin; cellular senescence; senomorphics
    DOI:  https://doi.org/10.1002/advs.202412950
  8. Aging Cell. 2025 Apr 22. e70060
      Analysis of existing lifespan-extending geroprotective compounds suggested that polypharmacological compounds are the most effective geroprotectors, specifically those that bind multiple biogenic amine receptors. To test this hypothesis, we used graph neural networks to predict polypharmacological geroprotectors and evaluated them in Caenorhabditis elegans. Over 70% of the selected compounds extended lifespan, with effect sizes in the top 5% compared to all geroprotectors recorded in the DrugAge database. Thus, our study reveals that rationally designing polypharmacological compounds enables the design of geroprotectors with exceptional efficacy.
    Keywords:  Chemprop; GPCRs; aging; artificial intelligence; drug discovery; geroprotector; longevity; machine learning; polypharmacology
    DOI:  https://doi.org/10.1111/acel.70060
  9. Aging Cell. 2025 Apr 24. e70071
      Extracellular vesicles (EVs) are secreted by most cell types, transmitting crucial signaling molecules like proteins, small RNAs, and DNA. We previously demonstrated that EVs from murine and human mesenchymal stem cells (MSCs) functioned as senomorphics to suppress markers of senescence and the inflammatory senescence-associated secretory phenotype (SASP) in cell culture and in aged mice. Here we demonstrate that EVs from additional types of human adult stem cells and embryonic progenitor cells have a senomorphic activity. Based on their miRNA profiles showing prevalence in stem cell EVs versus nonstem cell EVs and the number of age-related genes targeted, we identified eight miRNAs as potential senomorphic miRNAs. Analysis of these miRNAs by transfection into etoposide-induced senescent IMR90 human fibroblasts revealed that each of the miRNAs alone regulated specific senescence and SASP markers, but none had complete senomorphic activity. Evaluation of ~300 combinations of miRNAs for senotherapeutic activity identified a senomorphic cocktail of miR-181a-5p, miR-92a-3p, miR-21-5p, and miR-186-5p that markedly reduced the expression of p16INK4a, p21Cip1, IL-1β, and IL-6 and the percentage of SA-ß-gal-positive cells. Transcriptome analysis identified multiple pathways affected by the miRNA cocktail, including cellular senescence and inhibition of PCAF and HIPK2 in the p53 signaling pathway. Finally, treatment of aged mice with liposomes containing the four miRNA cocktail suppressed markers of senescence and inflammation in multiple tissues. These studies suggest that EVs derived from stem cells suppress senescence and inflammation, at least in part, through miRNAs and that a senomorphic miRNA cocktail could be used to target senescence and inflammation to extend health span.
    Keywords:  aging; antiaging; cellular senescence; molecular biology of aging; senescence
    DOI:  https://doi.org/10.1111/acel.70071
  10. Biogerontology. 2025 Apr 21. 26(3): 96
      Mesenchymal stem cells (MSCs) and blood plasma/MSC-derived extracellular vesicles (EVs) offer promising tools to promote longevity and treat age-related diseases. MSCs have low immunogenicity and tumorigenicity, and their efficacy is relatively independent of the donor age in humans (but not in rodents). Systemic administration of MSCs and stem cell/blood-derived EVs modified the omic profiles of various organs of aged rodents towards the young ones. The application of EVs appears to be even more beneficial than MSCs. Remarkably, over 70% of microRNAs, which are over-presented in ESC-derived EVs, were found to target longevity-associated genes. Along with MSCs, other types of stem cells were reported to display health- and lifespan-extending effects. Pluripotent Muse cells, a specific subpopulation of MSCs, which possess a number of unique features, could be particularly relevant for promoting healthspan. The rejuvenation potential of MSCs, EVs, and Muse cells warrants further investigation in both animal models and clinical trials, using aging clocks for biological age determination as one of the endpoints.
    Keywords:  Aging signatures; Cell therapy; Extracellular vesicles; Longevity; MSCs; Stem cells
    DOI:  https://doi.org/10.1007/s10522-025-10240-z
  11. Mar Drugs. 2025 Apr 11. pii: 165. [Epub ahead of print]23(4):
      Aging is a natural process resulting in the progressive impairment of multiple functions in the human body, leading to a decline in cellular functionality and the development of aging-related diseases. External stress factors, such as ultraviolet (UV) radiation, pollution, and toxin exposure, increase oxidative stress, damage cellular repair mechanisms, and speed up aging processes. With the rise in the world's aging population, there are enlarged demands for the use of sustainable natural products in food, nutrient supplements and cosmetics that can slow down aging and prolong healthy life and longevity. Algae, including both macroalgae and microalgae, have been recognised as a source of valuable proteins, amino acids, fatty acids, vitamins, and minerals useful for human consumption and medical applications. With increasing demands for nutraceutical and pharmaceutical bioproducts from environmentally friendly resources, the biotechnological industry, over recent decades, has had to provide new, advanced solutions using modern high-throughput omics technologies. The application of proteomics in the area of discoveries of natural products with anti-aging properties has become more popular for wide industry applications. New proteomics profiling provides a better understanding of changes occurring in protein and peptide content, their structure, function and interactions, as well as the regulatory processes and molecular pathways. Mass spectrometry-based proteomics has been used for a wide range of applications including protein identification, characterisation, as well as quantification of proteins within the proteome and sub-proteome. The application of chemical proteomics facilitated the identification of natural products approach and included the synthesis of probes and target fishing, allowing the advanced identification of proteins of interest. This review focuses on marine macro- and microalgal anti-aging compounds and novel proteomics approaches, providing recent experimental evidence of their involvement in anti-aging processes that should facilitate their use in innovative approaches and sustainable biotechnological applications.
    Keywords:  algae; anti-aging; bioactive compounds; proteomics; skin care
    DOI:  https://doi.org/10.3390/md23040165
  12. Int J Biol Macromol. 2025 Apr 21. pii: S0141-8130(25)03934-0. [Epub ahead of print] 143382
      Bletilla striata polysaccharide (BSP) is a natural bioactive compound known for its promising health benefits, including antioxidant, immunomodulatory, and anti-inflammatory effects. However, its potential in combating aging remains largely unexplored. This study aims to investigate the anti-aging effects of BSP in the Drosophila melanogaster model. The results show that BSP supplementation significantly extends the lifespan of flies in a concentration-dependent manner, with the most pronounced effects observed at a concentration of 3 mg/mL. Lifespan extension is associated with enhanced antioxidative capacities, as evidenced by increased SOD and CAT activities, and decreased MDA content. Additionally, BSP ameliorates age-related symptoms, including improved climbing ability and enhanced intestinal barrier function. Furthermore, BSP supplementation enhances resistance to H2O2-induced oxidative and starvation stresses, attenuates the lead (Pb)-induced toxicity, and delays the onset of Alzheimer's phenotypes in flies. RNA-Seq analysis reveals that BSP supplementation leads to the differential expression of 992 genes. KEGG pathway analysis highlights significant changes in metabolic pathways, including galactose metabolism, starch and sucrose metabolism, and carbon metabolism. Key genes such as Mal-A1, Amy-d, Men-b, Pgm-1, Mdh1, and Hex-C are downregulated, while CG32026, CG11291, and Ald2 are upregulated. These findings suggest BSP exhibits significant anti-aging and protective properties, making it a potential therapeutic agent.
    Keywords:  Alzheimer's disease; Anti-aging; Antioxidant; Bletilla striata polysaccharide; Drosophila melanogaster; Intestinal homeostasis; Oxidative stress
    DOI:  https://doi.org/10.1016/j.ijbiomac.2025.143382
  13. Aging Cell. 2025 Apr 21. e70068
      Senescent cells emerge with aging and injury. The contribution of senescent cells to DNA methylation age (DNAmAGE) in vivo is uncertain. Furthermore, stem cell therapy can mediate "rejuvenation", but how tissue regeneration controlled by resident stem cells affects whole tissue DNAmAGE is unclear. We assessed DNAmAGE with or without senolytics (BI01) in aged male mice (24-25 months) 35 days following muscle healing (BaCl2-induced regeneration versus non-injured). Young injured mice (5-6 months) without senolytics were comparators. DNAmAGE was decelerated by up to 68% after injury in aged muscle. DNAmAGE was modestly but further significantly decelerated by injury recovery with senolytics. ~1/4 of measured CpGs were altered by injury then recovery regardless of senolytics in aged muscle. Specific methylation changes caused by senolytics included differential regulation of Col, Hdac, Hox, and Wnt genes, which likely contributed to improved regeneration. Altered extracellular matrix remodeling using histological analysis aligned with the methylomic findings with senolytics. Without senolytics, regeneration had a contrasting effect in young mice and tended not to influence or modestly accelerate DNAmAGE. Comparing young to old injury recovery without senolytics using methylome-transcriptome integration, we found a more coordinated molecular profile in young and differential regulation of genes implicated in muscle stem cell performance: Axin2, Egr1, Fzd4, Meg3, and Spry1. Muscle injury and senescent cells affect DNAmAGE and aging influences the transcriptomic-methylomic landscape after resident stem cell-driven tissue reformation. Our data have implications for understanding muscle plasticity with aging and developing therapies aimed at collagen remodeling and senescence.
    Keywords:  DNAmAGE; aging; extracellular matrix; methylation clock; omics integration
    DOI:  https://doi.org/10.1111/acel.70068
  14. J Cosmet Dermatol. 2025 Apr;24(4): e70196
       BACKGROUND: Facial skin aging is a cumulative result of both intrinsic and extrinsic stressors. Chemical peels are commonly performed noninvasive skin rejuvenation procedures targeting these stressors. Innovation in chemical peels has remained limited, creating an opportunity for the industry to evolve with next-generation technology.
    AIMS: A novel topical antioxidant biostimulating treatment (ABT) was developed that utilizes a typical chemoexfoliation base as a vehicle to deliver a unique blend of antioxidant biostimulating acidic phytocompounds (ABAP). It was hypothesized that controlled delivery of ABAP could occur through a typical AHA/BHA chemical peel vehicle. These ABAPs, such as asiatic, ursolic, madecassic, and oleanolic acids, are known for skin rejuvenation in the papillary dermis.
    PATIENTS/METHODS: The ABT was tested in both ex vivo and in vivo settings to elucidate its mechanism of action and determine its efficacy and safety on 32 female subjects aged 38-60 years with Fitzpatrick skin types I-V.
    RESULTS: The ABT upregulated elastin and collagen after superficial wounding of the skin by over 25% when compared to untreated or vehicle controls. Clinical evaluation by an expert grader demonstrated that the ABT significantly improved fine lines, wrinkles, tactile laxity, and overall appearance after three ABT sessions. Clinical photography demonstrated an improvement in fine lines, wrinkles, skin smoothness, laxity, radiance, and overall appearance.
    CONCLUSIONS: The ABT developed with ABAP technology was efficacious in improving facial skin aging for skin rejuvenation and safe for all skin tones.
    Keywords:  aesthetic dermatology; antioxidant; collagen; elastin; skin rejuvenation
    DOI:  https://doi.org/10.1111/jocd.70196
  15. Biogerontology. 2025 Apr 25. 26(3): 97
      Vorinostat, a pan histone deacetylases (HDACs) inhibitor clinically approved for cutaneous T-cell lymphoma, exerts therapeutic effects by inducing tumor cell death and cycle arrest. Intriguingly, a previously unrecognized hormetic role of low-dose vorinostat in Caenorhabditis elegans. Subtoxic concentrations of vorinostat (1 μM) significantly extended lifespan, enhanced healthspan, and improved resistance to oxidative and heat stress, while ameliorating Aβ-induced paralysis. qPCR analysis demonstrated dose-dependent bidirectional regulation of stress-resistance genes (sod-3, hsp-16.2, skn-1, gst-4, act-1), with low doses of vorinostat upregulating these genes whereas higher doses (10 μM) exerted suppressive or neutral effects. Mechanistically, vorinostat-induced hormesis required functional SKN-1 signaling, as evidenced by its capacity to activate skn-1 and downstream targets (hsp-16.2, gst-4, act-1). Crucially, RNAi-mediated skn-1 knockdown completely abolished the pro-longevity and stress-resistant phenotypes. These findings establish vorinostat as a novel hormetin that enhances organismal resilience through SKN-1 pathway activation, providing new insights into HDAC inhibitor biology and aging intervention strategies.
    Keywords:  Hormetin, hormesis; Lifespan; SKN-1; Stress resistance; Vorinostat
    DOI:  https://doi.org/10.1007/s10522-025-10236-9
  16. Phytother Res. 2025 Apr 21.
      Vascular aging is a major contributor to age-related cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) induced early arterial aging and excessive senescent cells (SCs) burden in vessels. Inhibiting cellular senescence or eliminating SCs could effectively improve aging-related CVDs. Fisetin, a flavonoid extracted from cotinus coggygria scop, has shown potential in alleviating aging by clearing SCs. This study investigated the unexplored mechanisms and efficacy of fisetin in alleviating T2DM-related aortic aging. The T2DM mouse model was induced using a high-fat diet and low-dose streptozotocin injection. Chronic fisetin treatment's protective effects against aortic aging were assessed via senescence-associated beta-galactosidase (SA-β-Gal) staining, histopathology, and vasomotor function. RNA-sequencing and western blotting identified relevant signaling pathways and protein expression. Fisetin's effects on SCs and senescence-associated secretory phenotype (SASP) factors were evaluated through cell viability, apoptosis, and co-culture assays. Docking simulations suggested fisetin as a potential Phosphoinositide 3-kinase (Pi3k) inhibitor. In vivo, chronic fisetin treatment reduced aortic SCs burden, alleviating T2DM-related and natural aortic aging. In vitro, fisetin selectively induced apoptosis of senescent endothelial cells via regulating the Pi3k-Protein Kinase B (Akt)-B-cell lymphoma (Bcl)-2/Bcl-xl pathway and suppressed SASP and its detrimental effects. Furthermore, fisetin combined with metformin therapy showed superior anti-aging effects on T2DM-related aortic aging compared to metformin monotherapy. In conclusion, chronic fisetin treatment alleviates T2DM-related aortic aging via clearing the SCs burden and abrogating the SASP factors. Fisetin combined with metformin therapy might be a potential therapeutic strategy for T2DM-related CVDs.
    Keywords:  T2DM; aging; fisetin; senescence; senolytic
    DOI:  https://doi.org/10.1002/ptr.8507
  17. Cell Prolif. 2025 Apr 18. e70044
      As maternal age increases, the decline in oocyte quality emerges as a critical factor contributing to reduced reproductive capacity, highlighting the urgent need for effective strategies to combat oocyte aging. This study investigated the protective effects and underlying mechanisms of Echinacoside (ECH) on aging oocytes. ECH significantly improved cytoskeletal stability and chromosomal integrity, as demonstrated by restored spindle morphology and reinforced F-actin structures, essential for meiotic progression. It also preserved mitochondrial function by restoring membrane potential and dynamics, reducing ROS levels, and downregulating the DNA damage marker γ-H2AX, thereby alleviating oxidative stress and enhancing genomic stability. Furthermore, ECH promoted cellular homeostasis through modulation of lipid metabolism, autophagy and lysosomal function. Transcriptomic analyses identified GJA1 as a pivotal mediator of ECH's effects, validated through molecular docking and bio-layer interferometry. Functional studies showed that inhibiting GJA1 significantly reduced ECH's ability to enhance first polar body extrusion rates, mitochondrial function and antioxidant capacity, validating the critical role of the GJA1/SIRT1 pathway in combating oocyte aging. This study provides novel insights into the mechanisms of oocyte rejuvenation and highlights ECH as a promising therapeutic candidate for addressing age-related reproductive challenges.
    Keywords:  GJA1/SIRT1 pathway; cellular homeostasis; echinacoside; mitochondrial function; oocyte aging; oxidative stress
    DOI:  https://doi.org/10.1111/cpr.70044
  18. Gels. 2025 Apr 09. pii: 281. [Epub ahead of print]11(4):
      Hyaluronic acid (HA) is a linear, unbranched polysaccharide classified as a glycosaminoglycan. While HA is found in various tissues throughout the body, over half of its total proportion is found in the skin. The role of HA in the skin is complex and multifaceted. HA maintains proper hydration, elasticity, and skin firmness, serving as a key extracellular matrix (ECM) component. With age, HA production gradually decreases, leading to reduced water-binding capacity, drier and less elastic skin, and the formation of wrinkles. Additionally, HA plays an active role in the wound-healing process at every stage. This review summarizes the current background knowledge about the role of HA in skin aging and wound healing. We discuss the latest applications of HA in aging prevention, including anti-aging formulations, nutricosmetics, microneedles, nanoparticles, HA-based fillers, and skin biostimulators. Furthermore, we explore various HA-based dressings used in wound treatment, such as hydrogels, sponges, membranes, and films.
    Keywords:  hyaluronic acid; skin aging; wound healing
    DOI:  https://doi.org/10.3390/gels11040281
  19. J Appl Biomater Funct Mater. 2025 Jan-Dec;23:23 22808000251330974
      Oligopeptides, composed of 2-10 amino acid residues, are protein fragments with unique structural characteristics, including small molecular size, high biocompatibility, and modifiable functional groups. These features endow oligopeptides with excellent permeability, safety, and versatile biological activities, making them widely applicable in disease treatment, drug delivery, and skincare. In particular, oligopeptides have emerged as advanced ingredients in skincare, offering anti-aging, anti-wrinkle, and whitening effects by regulating key biological processes such as collagen synthesis, antioxidant defense, and melanin production. This review comprehensively discusses the structural properties, functional mechanisms, and diverse applications of oligopeptides and their derivatives, highlighting their potential in skin regeneration, rejuvenation, and anti-aging medicine. By providing insights into the latest advancements, this review aims to serve as a valuable reference for future research and development in oligopeptide-based therapeutics and skincare innovations.
    Keywords:  oligopeptides; rejuvenation; skin regeneration
    DOI:  https://doi.org/10.1177/22808000251330974
  20. BMC Res Notes. 2025 Apr 24. 18(1): 195
       OBJECTIVES: Increasing longevity and the growing elderly population necessitate a deeper understanding of aging mechanisms to prolong productive life and improve treatments for age-related diseases linked with cellular senescence. Mesenchymal stem cells (MSCs) are crucial for maintaining tissue homeostasis, but their physiological changes during senescence are not well understood. Growth differentiation factor 11 (GDF11) has emerged as a potential rejuvenation factor, enhancing MSC viability, mobility, and angiogenic functions, which improves outcomes in ischemic models and cardiac repair. This study aims to identify transcriptomic changes in young and senescent MSCs influenced by GDF11, highlighting its potential in MSC-based therapies.
    DATA DESCRIPTION: To evaluate transcriptomic changes induced by the potential geroprotective factor GDF11, we performed RNA sequencing on four groups of samples: 'young' MSCs (MmC-/GDF11-) and senescent MSCs (MmC+/GDF11-) without the addition of GDF11, as well as 'young' (MmC-/GDF11+) and senescent MSCs (MmC+/GDF11+) with the addition of GDF11. After 10 days of incubation, indexed cDNA libraries for Illumina sequencing were prepared from the samples, and the resulting cDNA library mix was subjected to NovaSeq 6000 sequencing. This paper describes the collection of 16 RNA sequencing samples comprising 4 sets of MSCs. FASTQ files from Illumina sequencing are available in the NCBI Gene Expression Omnibus.
    Keywords:  Cell senescence; GDF11; Geroprotectors; MSCs; Mesenchymal stem cells; RNA-sequencing; Transcriptome
    DOI:  https://doi.org/10.1186/s13104-025-07262-8
  21. Front Genome Ed. 2025 ;7 1558432
      CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) has emerged as a transformative genome-editing tool with significant therapeutic potential for age-related diseases, including Alzheimer's disease, Parkinson's disease, cardiovascular disorders, and osteoporosis. This study presents a bibliometric analysis of CRISPR-Cas9 research in age-related diseases, identifying key contributors, major research hotspots, and critical technological advancements. While promising applications have been demonstrated in gene repair, functional regulation, and molecular interventions, significant barriers persist, including off-target effects, low delivery efficiency, and limited editing in non-dividing cells. Ethical concerns over germline editing and gaps in long-term safety data further complicate clinical translation. Future directions emphasize the development of high-precision Cas9 variants, homology-directed repair-independent tools, and efficient delivery systems, alongside the establishment of international regulatory frameworks and multicenter clinical trials. These efforts are essential to fully realize the potential of CRISPR-Cas9 in addressing the global health challenges of aging.
    Keywords:  CRISPR-Cas9; age-related diseases; bibliometric analysis; gene therapy; genome editing
    DOI:  https://doi.org/10.3389/fgeed.2025.1558432
  22. PNAS Nexus. 2025 Apr;4(4): pgaf103
      Aging has been identified as a leading risk factor for many diseases, including neurodegenerative disorders. While cellular senescence has been linked to age-related neurodegenerative conditions, its involvement in peripheral stress-associated brain disorders is just beginning to be explored. In this study, we investigated the impact of senescent cells on peripheral stress-induced neuroinflammation using orthopedic surgery as a model. Our results demonstrate an increased accumulation of senescent cells and neuroinflammation in the aged mouse hippocampus following surgery. Intermittent treatment of the mice with the senolytic drugs dasatinib and quercetin (D/Q) showed a significant reduction in surgery-induced senescent cell burden. This reduction in senescent cell accumulation was correlated with reduced surgery-induced neuroinflammation, as evidenced by decreased glial cell activity. Consistent with these observations, we also observed reduced levels of proinflammatory senescence-associated secretory phenotype factors in circulation, following fracture surgery, in mice treated with D/Q. Overall, our findings underscore the pivotal role of cellular senescence in surgery-induced neuroinflammation and highlight the therapeutic potential of eliminating senescent cells as a potential strategy to manage peripheral stress-induced neuroinflammatory conditions.
    Keywords:  cellular senescence; inflammaging; neuroinflammation; orthopedic trauma; senolytics
    DOI:  https://doi.org/10.1093/pnasnexus/pgaf103
  23. Front Aging. 2025 ;6 1549453
      Aging is a complex biological process characterized by functional decline, reduced quality of life, and increased vulnerability to diseases such as type 2 diabetes, cardiovascular conditions, neurodegeneration, and cancer. Advances in medical technology have introduced the concept of aging therapies, with growth hormone (GH) and its primary mediator, insulin-like growth factor 1 (IGF-1), receiving considerable attention for their potential to counteract age-related physiological and metabolic changes. GH plays a multifaceted role in the human body, primarily influencing body composition by increasing muscle mass, reducing fat tissue, promoting bone formation, and regulating the metabolism of proteins, lipids, and glucose. Additional effects have been noted on endothelial function, cognitive performance, and circadian rhythms. This review examines the molecular mechanisms of GH in aging, its potential as an anti-aging therapy, and findings from clinical trials involving these hormones for this purpose. It also addresses the associated adverse effects, limitations, and controversies. While some studies report significant benefits, these therapies' long-term safety and efficacy in promoting healthy aging remain uncertain, highlighting the need for further research.
    Keywords:  aging; anti-aging treatments; human growth hormone; human growth hormone deficiency; insulin-like growth factor I
    DOI:  https://doi.org/10.3389/fragi.2025.1549453
  24. Front Pharmacol. 2025 ;16 1550357
       Background: The phenomenon of population aging presents a significant global challenge, with the aging population in China steadily increasing. As individuals progress in age, there is a gradual deterioration of human organs and systems, as well as a decline in the immune system, referred to as immunosenescence. Atractylodis macrocephalae rhizoma (BZ) has been historically used in China for its medicinal properties, including gastrointestinal improvement, immunomodulation, anti-aging, antioxidant effects, and anti-tumor effects. Nevertheless, there remains a gap in understanding the pharmacological and molecular mechanisms underlying its anti-immunosenescence effects.
    Methods: This study employed UPLC-ESI-MS and network pharmacology to create a network map of BZ ultrafine powder (BZU) and its aging targets. Enrichment analysis was then used to identify the primary mechanistic pathways underlying BZU's anti-immunosenescence effects. The primary components of BZU were quantitatively analyzed using high-performance liquid chromatography (HPLC). Naturally aging rats were used to examine the effects of different oral doses (0.25, 0.5, and 1 g/kg) of BZU over 5 weeks on aging performance, peripheral blood immunophenotyping and cell count, and splenic lymphocyte proliferation rate. To validate the findings of network pharmacology, quantitative RT-PCR, Western blotting, and immunofluorescence analyses were conducted.
    Results: Our analyses demonstrated that BZU improved various indicators of aging in naturally aging rats, such as increasing the number of voluntary activities, enhance grip strength and fatigue resistance, increasing the microcirculatory blood flow and improving hematological levels. The BZU administration enhanced T and B lymphocyte proliferation and significantly improved the lymphocyte-to-T cell subpopulation ratio. It can elevate serum IL-2 and IL-4 levels while reducing IL-6, IFN-γ and TNF-α levels in naturally aging rats. Finally, it increased CD3 protein expression in the spleen while decreasing protein levels of PI3K, p-AKT, IKKα/β, and NF-κB. It also decreased the mRNA expression of Pik3cg, Akt1, Pdk1 and Nfκb1.
    Conclusion: These findings suggest that BZU may enhance lymphocyte proliferation by inhibiting the PI3K/Akt/NF-κB signaling pathway, correcting immune cell imbalances, reducing inflammatory responses, and ultimately enhancing immune function and potentially delaying aging.
    Keywords:  Atractylodis macrocephalae rhizoma; PI3K/Akt/NF-κB; aged; immunosenescence; network pharmacology
    DOI:  https://doi.org/10.3389/fphar.2025.1550357
  25. Elife. 2025 Apr 23. pii: RP100737. [Epub ahead of print]13
      Neurodegenerative diseases are age-related disorders characterized by the cerebral accumulation of amyloidogenic proteins, and cellular senescence underlies their pathogenesis. Thus, it is necessary for preventing these diseases to remove toxic proteins, repair damaged neurons, and suppress cellular senescence. As a source for such prophylactic agents, we selected zizyphi spinosi semen (ZSS), a medicinal herb used in traditional Chinese medicine. Oral administration of ZSS hot water extract ameliorated Aβ and tau pathology and cognitive impairment in mouse models of Alzheimer's disease and frontotemporal dementia. Non-extracted ZSS simple crush powder showed stronger effects than the extract and improved α-synuclein pathology and cognitive/motor function in Parkinson's disease model mice. Furthermore, when administered to normal aged mice, the ZSS powder suppressed cellular senescence, reduced DNA oxidation, promoted brain-derived neurotrophic factor expression and neurogenesis, and enhanced cognition to levels similar to those in young mice. The quantity of known active ingredients of ZSS, jujuboside A, jujuboside B, and spinosin was not proportional to the nootropic activity of ZSS. These results suggest that ZSS simple crush powder is a promising dietary material for the prevention of neurodegenerative diseases and brain aging.
    Keywords:  aging; dementia; medicine; mouse; neurodegenerative disease; neuroscience; rejuvenation; senescence; traditional Chinese medicine
    DOI:  https://doi.org/10.7554/eLife.100737
  26. Front Pharmacol. 2025 ;16 1545585
       Background: Age-related decline in nicotinamide adenine dinucleotide (NAD+)-a central regulator of cellular metabolism, DNA repair, and immune homeostasis-is strongly associated with physiological dysfunction. Nicotinamide mononucleotide (NMN), a potent NAD+ precursor, shows promise in counteracting aging-related pathologies, particularly neurodegenerative decline.
    Methods: An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation. Behavioral outcomes (open field test, Morris water maze) were analyzed alongside oxidative stress markers (SOD, CAT, AGEs), inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10), and neurotransmitters (LC-MS/MS). Apoptotic activity (TUNEL, p16/p21), mitochondrial regulators (Sirt1, p-AMPK, PGC-1α), and intestinal barrier integrity (HE/AB-PAS staining) were evaluated. Sirt1 dependency was confirmed using inhibitor Ex527.
    Results: NMN restored locomotor activity and spatial memory in D-gal mice without altering body weight. Mechanistically, NMN synergistically attenuated oxidative stress and systemic inflammation, elevating antioxidant enzymes (SOD, CAT) and IL-10 while suppressing pro-inflammatory cytokines (TNF-α, IL-6) and AGEs. Cortical/hippocampal analyses revealed reduced apoptosis (TUNEL+ cells) and senescence markers (p16, p21), with enhanced mitochondrial function via Sirt1/AMPK/PGC-1α activation (Sirt1, p-AMPK). NMN concurrently preserved intestinal mucosal architecture, mitigating D-gal-induced barrier disruption. Crucially, all benefits were abolished by Sirt1 inhibition, confirming pathway specificity.
    Conclusion: Our findings establish NMN as a multifaceted therapeutic agent that preserves neurocognitive function and intestinal homeostasis in aging models by orchestrating antioxidative, anti-inflammatory, and antiapoptotic responses through Sirt1/AMPK/PGC-1α activation. This work provides translational insights into NAD+-boosting strategies for age-related disorders.
    Keywords:  NMN; SIRT1; aging; intestinal barrier; neuroinflammation; oxidative stress
    DOI:  https://doi.org/10.3389/fphar.2025.1545585
  27. Food Sci Nutr. 2025 Apr;13(4): e70161
      Aging is an intricate pathophysiological phenotype. It is the result of the combined action of various inflammatory factors and cytokines. Aging is closely related to inflammation, apoptosis, tumors, and other diseases. Anthocyanins are a kind of natural flavonoid, mainly contained in plant fruits such as bilberry, grape, purple sweet potato, and so on. These flavonoids have antioxidation, antiaging, and anti-inflammatory properties. It has been found that anthocyanins can effectively delay liver, ovary, and other organ aging. However, the biological mechanism by which anthocyanins alleviate aging phenotypes is still poorly understood. To simulate liver aging in mice, D-galactose was injected daily at 800 mg/kg to accelerate aging, and anthocyanins at 20 or 40 mg/kg were given as intervention treatments. The antiaging effect of anthocyanins was evaluated by body weight, inflammatory markers, and aging markers. Serum ALT and AST levels were measured, and liver histology was assessed using hematoxylin-eosin staining. In addition, we explored the molecular mechanism of anthocyanins delaying liver aging by detecting the expression levels of NF-κB/IKK signaling protein molecules. Our results indicate that anthocyanins can effectively delay mouse liver senescence induced by D-galactose. Analyses by Western blot demonstrated that anthocyanins inhibited the NF-κB/IKK signaling pathway, thereby inhibiting inflammation. In vitro, anthocyanins attenuate the D-galactose (D-gal)-induced aging in AML12 cells, as indicated by reduced aging-associated p21 and p16. Anthocyanins can similarly inhibit the NF-κB/IKK signal pathway in D-gal-induced aging in AML12 cells. Based on these findings, anthocyanins reduce liver aging in mice by regulating the NF-κB/IKK pathway.
    Keywords:  NF‐κB/IKK signaling pathway; aging; anthocyanins; inflammation; liver
    DOI:  https://doi.org/10.1002/fsn3.70161
  28. Front Cell Dev Biol. 2025 ;13 1545167
      Vitamin D has the potential to therapeutically affect the endocrine parameters of premature ovarian insufficiency (POI) patients. Previous research has indicated that serum vitamin D levels tend to decline with age and in individuals with POI. However, the precise impact of vitamin D deficiency on female fertility, especially their ovarian function, remains unclear. Vitamin D receptor (VDR) deficiency mice provide a model to investigate the possible effect of vitamin D on female reproduction. In this study, we observed abnormal follicular development in the Vdr deficiency mice. This anomaly is associated with reduced expression of anti-Mullerian hormone (AMH) and disrupted aromatase expression that disrupts the hormone secretion. Moreover, our findings indicate that Vdr deficiency disturbs redox balance, resulting in oxidative stress in the ovary, which further suppresses granulosa cell function and accelerates ovarian aging. Mechanistically, loss of Vdr inhibits de novo cholesterol synthesis by transcriptional repression of Hmgcr, and the antioxidant and anti-aging effects of the intermediate product 7-dehydrocholesterol (7-DHC) are also decreased. Treatment with 7-DHC effectively reduces ROS levels and alleviates aging in KGN cells deficient in Vdr. In conclusion, our results show that Vdr deficiency impairs follicle maturation and hormone secretion by accelerating granulosa cell aging, as a result of the reduced antioxidant and anti-aging effect of 7-DHC.
    Keywords:  7-dehydrocholesterol (7-DHC); VDR; aging; granulosa cell; premature ovarian insufficiency (POI)
    DOI:  https://doi.org/10.3389/fcell.2025.1545167
  29. Cells. 2025 Apr 17. pii: 608. [Epub ahead of print]14(8):
      Cellular senescence regulates aging, tissue maintenance, and disease progression through the Senescence-Associated Secretory Phenotype (SASP), a secretory profile of cytokines, chemokines, growth factors, and matrix-remodeling enzymes. While transient SASP aids wound healing, its chronic activation drives inflammation, fibrosis, and tumorigenesis. This review examines SASP's molecular regulation, dual roles in health and pathology, and therapeutic potential. The following two main strategies are explored: senescence clearance, which eliminates SASP-producing cells, and SASP modulation, which refines secretion to suppress inflammation while maintaining regenerative effects. Key pathways, including NF-κB, C/EBPβ, and cGAS-STING, are discussed alongside pharmacological, immunotherapeutic, gene-editing, and epigenetic interventions. SASP heterogeneity necessitates tissue-specific biomarkers for personalized therapies. Challenges include immune interactions, long-term safety, and ethical considerations. SASP modulation emerges as a promising strategy for aging, oncology, and tissue repair, with future advancements relying on multi-omics and AI-driven insights to optimize clinical outcomes.
    Keywords:  SASP modulation strategies; aging and tissue homeostasis; cellular rejuvenation; cellular senescence; senescence-associated secretory phenotype (SASP)
    DOI:  https://doi.org/10.3390/cells14080608
  30. Biosensors (Basel). 2025 Apr 05. pii: 232. [Epub ahead of print]15(4):
      In the 21st century, the demographic shift toward an aging population has posed a significant challenge, particularly with respect to age-related diseases, which constitute a major threat to human health. Accordingly, the detection, prevention, and treatment of aging and age-related diseases have become critical issues, and the introduction of novel molecular recognition elements, called aptamers, has been considered. Aptamers, a class of oligonucleotides, can bind to target molecules with high specificity. In addition, aptamers exhibit superior stability, biocompatibility, and applicability, rendering them promising tools for the diagnosis and treatment of human diseases. In this paper, we present a comprehensive overview of aptamers, systematic evolution of ligands by exponential enrichment (SELEX), biomarkers associated with aging, as well as aptamer-based diagnostic and therapeutic platforms. Finally, the limitations associated with predicting and preventing age-related conditions are discussed, along with potential solutions based on advanced technologies and theoretical approaches.
    Keywords:  age-related disease; aging; aptamer; circadian rhythm; diagnosis; therapeutics
    DOI:  https://doi.org/10.3390/bios15040232
  31. Mar Drugs. 2025 Apr 08. pii: 162. [Epub ahead of print]23(4):
      Microalgae are a promising source of bioactive compounds, particularly proteins and peptides, with potential applications in skin health and the cosmetic industry. This study investigated the antioxidant and anti-aging properties of peptide fractions derived from Spirulina platensis and Chlorella vulgaris. Both microalgae were cultivated, and their proteins were subsequently extracted, enzymatically hydrolyzed with alcalase, and fractionated through ultrafiltration. Alkaline extraction yielded 82% protein from S. platensis and 72% from C. vulgaris. Enzymatic hydrolysis predominantly yielded <3 kDa peptides, which exhibited strong antioxidant activity reaching 78% for 2,2-diphenyl-1-picrylhidrazol (DPPH), 82% for 2,2'-azinobis-3-etilbenzothiazoline-6-sulfonic acid (ABTS), and 74% for ferric reducing antioxidant power (FRAP), with IC50 values as low as 23.44 µg/mL for ABTS inhibition in C. vulgaris. These peptides also significantly inhibited skin-aging enzymes, showing 84% inhibition of elastase, 90% of collagenase, and 66% of tyrosinase. Mass spectrometry and GNPS molecular networking of the <3 kDa fraction identified several di- and tri-peptides, including Lys-Val, Val-Arg, His-Ile, Lys-Leu, Ile-Leu, and Leu-Phe, Tyr-Phe, and Leu-Gly-Leu, potentially contributing to these bioactivities. These findings suggest that the enzymatic hydrolysis of S. platensis and C. vulgaris proteins provides a sustainable and natural source of bioactive peptides for antioxidant and anti-aging applications in food, pharmaceutical, and cosmetic industries.
    Keywords:  Chlorella vulgaris; Spirulina platensis; anti-aging function; antioxidant activity; bioactive peptides; enzymatic hydrolysis
    DOI:  https://doi.org/10.3390/md23040162
  32. Phytomedicine. 2025 Apr 15. pii: S0944-7113(25)00411-8. [Epub ahead of print]142 156772
       BACKGROUND: Age-related hearing loss (ARHL) is a prevalent sensory deficit that significantly affects quality of life in older individuals. Cellular senescence contributes to various age-related degenerative disorders. However, its effect on ARHL remains unclear.
    PURPOSE: The aim of this study was to explore the therapeutic potential of senolytics in attenuating cochlear senescence and delaying the progression of ARHL.
    METHODS: The senolytic drugs dasatinib and quercetin (D + Q) were used to target senescent cells at different stages of ARHL in C57BL/6J mice. The impact of D + Q treatment on ARHL progression and cochlear degeneration was also assessed. Additionally, the protective effects of D + Q treatment were evaluated in HEI-OC1 auditory cells and cochlear explants. Transcriptomic analysis was conducted on cochlear explants subjected to different treatments.
    RESULTS: D + Q treatment at an early stage of ARHL significantly delayed ARHL progression and alleviated cochlear degeneration in male and female C57BL/6J mice. Treatment of mice with normal hearing also mitigated age-related hair cell loss. In HEI-OC1 auditory cells, D + Q treatment exerted protective effects by alleviating the senescence-associated secretory phenotype (SASP). Transcriptomic analysis of cochlear explants revealed that downregulation of inflammatory cytokines and chemokines was involved in the beneficial effects of D + Q treatment against cellular senescence. Mechanistically, D + Q treatment alleviated hair cell senescence via binding to NF-κB and inhibiting its activity.
    CONCLUSION: Senolytics may offer a novel therapeutic strategy for attenuating cochlear senescence and slowing the progression of ARHL.
    Keywords:  Cellular senescence; Dasatinib; Hearing loss; Inflammation; NF-κB; Quercetin
    DOI:  https://doi.org/10.1016/j.phymed.2025.156772
  33. Aging Cell. 2025 Apr 24. e70039
      The mitochondrial translocator protein (TSPO) is a biomarker of inflammation associated with neurodegenerative diseases, widely regarded to be upregulated in the aging brain. Here we investigated the interaction between aging and TSPO immunomodulatory function in the mouse hippocampus, a region severely affected in Alzheimer's Disease (AD). Surprisingly, we found that TSPO levels were decreased in brain innate immune populations in aging. Aging resulted in a reversal of TSPO knockout transcriptional signatures following inflammatory insult. TSPO deletion drastically exacerbated inflammatory transcriptional responses in the aging hippocampus, while dampening inflammation in the young hippocampus. This age-dependent effect of TSPO was linked to NF-kβ and interferon regulatory transcriptional networks. Drugs that disrupt the cell cycle and induce DNA damage, such as heat shock protein and topoisomerase inhibitors, were identified to mimic the inflammatory transcriptional signature characterizing aging in TSPO knockout mice most closely. These findings indicate that TSPO plays a protective role in brain aging. This TSPO-aging interaction is an important consideration in the interpretation of TSPO-targeted biomarker and therapeutic studies, as well as in vitro studies that cannot model the aging brain.
    Keywords:  LPS; aging; hippocampus; mitochondria; neuroinflammation; translocator protein
    DOI:  https://doi.org/10.1111/acel.70039
  34. Int Immunopharmacol. 2025 Apr 18. pii: S1567-5769(25)00669-1. [Epub ahead of print]156 114679
      Neurodegenerative diseases (NDDs) represent a rapidly escalating global health challenge, contributing significantly to the worldwide disease burden and posing substantial threats to public health systems across nations. Among the many risk factors for neurodegeneration, aging is the major risk factor. In the context of aging, multiple factors lead to the release of endogenous DNA (especially mitochondrial DNA, mtDNA), which is an important trigger for the activation of the cGAS-STING innate immune pathway. Recent studies have identified an increasing role for activation of the cGAS-STING signaling pathway as a driver of senescence-associated secretory phenotypes (SASPs) in aging and NDDs. The cGAS-STING pathway mediates the immune sensing of DNA and is a key driver of chronic inflammation and functional decline during the aging process. Blocking cGAS-STING signaling may reduce the inflammatory response by preventing mtDNA release and enhancing mitophagy. Targeted inhibition of the cGAS-STING pathway by biological macromolecules such as natural products shows promise in therapeutic strategies for age-related NDDs. This review aims to systematically and comprehensively introduces the role of the cGAS-STING pathway in age-related NDDs in the context of aging while revealing the molecular mechanisms of the cGAS-STING pathway and its downstream signaling pathways and to develop more targeted and effective therapeutic strategies for NDDs.
    Keywords:  Age-related neuroinflammation; Inhibitors; Neurodegenerative diseases; Senescence-associated phenotypes; cGAS–STING pathway
    DOI:  https://doi.org/10.1016/j.intimp.2025.114679
  35. Food Funct. 2025 Apr 22.
      Aging represents a significant global challenge characterized by persistent oxidative stress and dysregulated lipid metabolism. Crocin, the primary bioactive constituent of saffron (Crocus sativus L.), is widely utilized as a natural food colorant and exhibits potent anti-inflammatory and antioxidant properties. Previous studies have demonstrated crocin's antioxidative, neuroprotective and memory-enhancing effects in aged rats; however, its direct impact on aging and the underlying mechanisms remain unexplored. In this study, we demonstrated that crocin treatment extended lifespan, enhanced survival under heat and juglone-induced oxidative stress, and reduced lipofuscin accumulation in the model organism C. elegans. Mechanistically, crocin activated DAF-16, the C. elegans homolog of human FOXO, resulting in the upregulation of key antioxidant genes (gst-4, sod-3 and hsp-16.2). Notably, the lifespan-extension effect of crocin was abolished in a daf-16 mutant, and its antioxidant effects were significantly attenuated in daf-16 RNAi experiments conducted in N2, CL2166, CF1553 and TJ375 strains. Furthermore, crocin specifically reduced fat accumulation, and upregulated the expression of genes involved in lipid mobilization (lipl-3, lipl-4, atgl-1 and acs-2) and unsaturated fatty acid synthesis (fat-6 and elo-2) in aged nematodes. GC-MS analysis further demonstrated that crocin treatment elevated the levels of unsaturated fatty acids (C18:1n9, C20:4n-6, C20:4n-3 and C20:5n-3), an effect that was completely abolished under daf-16 knockdown conditions. Collectively, these findings suggest that crocin promotes longevity in C. elegans by mitigating oxidative stress and modulating lipid metabolism through the DAF-16/FOXO pathway. These results highlight the potential of crocin as a promising strategy for treating aging and age-related diseases.
    DOI:  https://doi.org/10.1039/d5fo01157d
  36. Aging Cell. 2025 Apr 25. e70062
      Aging is a major risk factor for cardiovascular diseases, and the accumulation of DNA damage significantly contributes to the aging process. This study aimed to identify the underlying molecular mechanisms of vascular aging in DNA-repair-deficient progeroid Ercc1Δ/- mice and to explore the therapeutic effect of dietary restriction (DR). RNA sequencing analysis revealed that DR reversed gene expression of vascular aging processes, including extracellular matrix remodeling, in the Ercc1Δ/- aorta. Notably, this analysis indicated the presence of macrophage-like vascular smooth muscle cells (VSMCs) and suggested cGAS-STING pathway activation. The presence of macrophage-like VSMCs and increased STING1 expression were confirmed in Ercc1Δ/- aortic tissue and were both reduced by DR. In vitro, cisplatin-induced DNA damage activated the cGAS-STING pathway in Ercc1Δ/- VSMCs but not in wildtype VSMCs. These findings identify the involvement of the cGAS-STING pathway in DNA damage-driven vascular aging and underscore the therapeutic benefits of DR for vascular aging. Furthermore, upstream regulator analysis revealed compounds that may replicate the beneficial effects of DR, providing promising leads for further investigation.
    Keywords:  DNA damage; Ercc1; cGAS‐STING; dietary restriction; intervention; macrophage‐like VSMCs; vascular aging
    DOI:  https://doi.org/10.1111/acel.70062
  37. Aging Biol. 2023 ;pii: 20230009. [Epub ahead of print]1
      Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disease caused by the mutant lamin-A protein "progerin," features robust sterile inflammation/interferon (IFN)-like response. Targeting inflammation delays cellular and organismal HGPS phenotypes. However, specific mechanisms driving the sterile inflammation/IFN-like response and how this response causes tissue degeneration/loss in HGPS are unknown. We demonstrate that signal transducer and activator of transcription 1 (STAT1) drives the IFN-like response and aging phenotypes in HGPS cellular and mouse models. Calcitriol and baricitinib strongly repress sterile inflammation/IFN-like response, improving hallmarks of progerin-expressing cells such as mitochondrial, autophagy, and proliferation defects. In vivo, calcitriol or baricitinib extend lifespan of progeria mice, and baricitinib alone or combined with a high-caloric/high-fat diet has a remarkable impact reducing skin, aortic, and adipose tissue degeneration. Critically, Stat1 haploinsufficiency reduces tissue degeneration/loss and extends lifespan of progeria mice, recapitulating baricitinib benefits. Our study unveils STAT1 as a driver of the IFN-like response and HGPS pathology and suggests that aberrant STAT1 signaling contributes to aging, providing new therapeutic possibilities for HGPS and other inflammation/IFN response-associated diseases.
    DOI:  https://doi.org/10.59368/agingbio.20230009
  38. J Gerontol A Biol Sci Med Sci. 2025 Apr 07. pii: glaf021. [Epub ahead of print]80(5):
    Participants of the NIA Heterogeneity and Successful Aging Workshop
      Heterogeneity in aging is a fundamental biological process arising from multifactorial etiologies, including genetic, lifestyle, and socioeconomic factors. Modeling this heterogeneity in animal systems is critical for elucidating the underlying mechanisms of aging and for leveraging these insights in translational research. Here we present part II, a summary of the model organism research presented at the NIA Heterogeneity and Successful Aging workshop, held in May 2023.
    Keywords:  Age-related pathology; Animal model; Anti-aging; Biodemography; Bioinformatics; Biology of aging; Frailty
    DOI:  https://doi.org/10.1093/gerona/glaf021
  39. J Invest Dermatol. 2025 Apr 20. pii: S0022-202X(25)00416-6. [Epub ahead of print]
      Keratinocyte differentiation is highly regulated to produce the stratified structure of the epidermis and must be balanced with cell proliferation. Our prior studies revealed that hairless mice that cannot synthesize vitamin C (VC) exhibit epidermal atrophy. VC is a cofactor for the DNA demethylation (TET) enzyme, but the role of VC in DNA demethylation during keratinocyte differentiation remains unclear. In this study, we evaluated the role of VC in epigenetic regulation of epidermal proliferation and differentiation in a human epidermal equivalent model. Our findings demonstrated that intracellular VC uptake increased epidermal thickness, cell proliferation, and global levels of 5-hydroxymethylcytosine (5-hmC) DNA. Notably, these effects of VC were attenuated by an inhibitor of the TET enzyme. DNA microarray and whole-genome bisulfite sequencing (WGBS) analyses revealed that twelve genes related to cell proliferation were significantly upregulated by VC. Further, hypomethylated DNA regions associated with these genes were revealed in the presence of VC. Collectively, our findings provide insight into how VC increases epidermal thickness by promoting keratinocyte proliferation via the DNA demethylation of proliferation-related genes. VC is a promising molecule that can be used as developing treatment for epidermal thinning, including in aging.
    Keywords:  aging; keratinocytes; skin health; skin structure and function
    DOI:  https://doi.org/10.1016/j.jid.2025.03.040
  40. Biogerontology. 2025 Apr 21. 26(3): 94
      Cardiac aging is a multistep process that results in a loss of various structural and functional heart abilities, increasing the risk of heart disease. Since its remarkable discovery in the early 1800s, when limestone is heated, calcium's importance has been defined in numerous ways. It can help stiffen shells and bones, function as a reducing agent in chemical reactions, and play a central role in cellular signalling. The movement of calcium ions in and out of cells and between those is referred to as calcium signalling. It influences the binding of the ligand, enzyme activity, electrochemical gradients, and other cellular processes. Calcium signalling is critical for both contraction and relaxation under the sliding filament model of heart muscle. However, with age, the heart undergoes changes that lead to increases in cardiac dysfunction, such as myocardial fibrosis, decreased cardiomyocyte function, and noxious disturbances in calcium homeostasis. Additionally, when cardiac tissues age, cellular senescence, a state of irreversible cell cycle arrest, accumulates and begins to exacerbate tissue inflammation and fibrosis. This review explores the most recent discoveries regarding the role of senescent cell accumulation and calcium signalling perturbances in cardiac aging. Additionally, new treatment strategies are used to reduce aged-related heart dysfunction by targeting senescent cells and modulating calcium homeostasis.
    Keywords:  Age-related cardiac dysfunction; Calcium signalling; Cardiac aging; Cardiomyocyte function; Cellular senescence; Myocardial fibrosis
    DOI:  https://doi.org/10.1007/s10522-025-10229-8