Biogerontology最新文献

{"title":"Therapeutic extracellular vesicles as a cornerstone of medicine in the next decade with gerontological focus.","authors":"Alexander Yu Pulver, Roman E Tokmachev, Natalie A Pulver, Lyubov N Antakova, Mariia A Emelianova","doi":"10.1007/s10522-025-10332-w","DOIUrl":"https://doi.org/10.1007/s10522-025-10332-w","url":null,"abstract":"<p><p>Extracellular vesicles present a promising alternative to stem cells in regenerative medicine and gerontology. They offer significant advantages over cell transplantation, demonstrating potential for slowing aging and treating age-related diseases. Extracellular vesicles secreted by diverse cell types modulate inflammation, stimulate tissue regeneration, and exhibit anti-inflammatory and immunomodulatory properties. This work explores the therapeutic potential of extracellular vesicles as alternatives to cell therapy, examining their key advantages and current limitations. It specifically focuses on their roles within established aging mechanisms and their dual utility as biomarkers and therapeutic agents. Critical aspects of extracellular vesicle translation are addressed, including standardized methods for production, storage stability optimization, and engineering strategies for cargo loading and targeting. Extracellular vesicles possess unique biological properties-inherent biocompatibility, low immunogenicity, ability to cross biological barriers, and high biological activity at low doses. Preclinical studies across various age-related pathologies (neurodegeneration, cardiovascular disease, sarcopenia) consistently report efficacy in reducing inflammation, promoting tissue repair, and improving functional outcomes. These findings strongly support the capacity of extracellular vesicles to mimic many therapeutic effects of parental cells while mitigating risks like tumorigenicity or immunorejection associated with whole-cell therapies. Overcoming challenges in scalable manufacturing, quality control, regulatory standardization, and targeted delivery is essential for the clinical translation of extracellular vesicles. Despite these hurdles, their compelling preclinical evidence and inherent advantages position them as a major future direction. They are expected to play a key role in combating age-related decline and advancing regenerative medicine, becoming a cornerstone of next-generation biomedical interventions over the next decade.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"190"},"PeriodicalIF":4.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"12-ethoxy-Marchantin A, a new macrocyclic bis-bibenzyl from Marchantia polymorpha L., exerts anti-aging activity through activating MAPKs-dependent Nrf2/HO-1 signaling pathways.","authors":"Bingjian Wu, Ge Ge, Jiaxin Xu, Yi Xing, Kun Hu, Jie Ren, Jia Yang","doi":"10.1007/s10522-025-10335-7","DOIUrl":"https://doi.org/10.1007/s10522-025-10335-7","url":null,"abstract":"<p><p>Phytochemicals represent emerging anti-aging therapeutic candidates, with Marchantia polymorpha L. (liverwort) gaining significant attention due to its broad-spectrum pharmacological properties. This plant exhibits remarkable wound-healing and regenerative capabilities, making it a promising candidate for the development of modern anti-aging drugs. In the presented study, 12-ethoxy-Marchantin A (EMA), a new macrocyclic bis-bibenzyl compound, was isolated and identified from M. polymorpha. Using a Lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7 macrophage model, a Caenorhabditis elegans (C. elegans) aging model, and network pharmacology analysis, we systematically investigated the pharmacological mechanisms underlying its anti-aging effects. Our results demonstrated that EMA significantly reduced inflammatory cytokines and nitric oxide (NO) in LPS-stimulated RAW264.7 cells via the nuclear factor erythroid 2-related factor 2 (Nrf2) / heme oxygenase (HO-1) pathway. Mechanistically, EMA triggered a reactive oxygen species (ROS)-mediated mitogen-activated protein kinase (MAPK)-dependent Nrf2 antioxidant signaling cascade. EMA significantly extended the lifespan and enhanced fecundity in the N2 strain of C. elegans, while reducing lipofuscin deposition and ROS levels. Additionally, EMA enhanced oxidative and heat stress resistance in the N2 strain of C. elegans. Network pharmacology revealed that its anti-aging effects may be mediated by MAPKs/Nrf2/HO-1 pathway regulation. Collectively, these findings highlight EMA as a potent anti-aging with therapeutic potential for aging-related conditions.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"189"},"PeriodicalIF":4.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chrysin, a glycolytic inhibitor, modulates redox homeostasis during aging via a potent calorie restriction mimetic effect in male wistar rats.","authors":"Akanksha Singh, Sakshi Jaiswal, Raushan Kumar, Nitin Mishra, Sandeep Kumar Yadav, Syed Ibrahim Rizvi","doi":"10.1007/s10522-025-10334-8","DOIUrl":"https://doi.org/10.1007/s10522-025-10334-8","url":null,"abstract":"<p><p>Chrysin (5,7-dihydroxyflavone), a natural flavonoid present in honey, propolis, and various medicinal plants, has shown promise as a calorie restriction mimetic (CRM) through its glycolysis-inhibiting action. This inhibition promotes a metabolic shift toward oxidative phosphorylation and fatty acid oxidation, potentially activating beneficial pathways like AMPK and SIRT1. The mechanism likely involves the downregulation of Hexokinase-2, leading to suppressed glycolysis and promotion of apoptosis. In this study, we assessed aging biomarkers in erythrocytes, plasma, and serum after administering chrysin (100 mg/kg, orally) and D-galactose (300 mg/kg, subcutaneously) for four weeks to Wistar rats. In the D-galactose-induced aging rat model, the markers of oxidative damage, such as protein carbonyls, malondialdehyde, and advanced oxidation protein products, were found to be elevated. However, chrysin treatment significantly upregulated antioxidant defenses, including catalase, superoxide dismutase, ferric-reducing antioxidant power (FRAP), and glutathione (GSH). Administration of chrysin to aged rats led to a decline in both inflammatory biomarkers and insulin concentrations. These findings suggest that chrysin can alleviate oxidative stress, reduce lipid peroxidation, and influence inflammation and metabolism, highlighting its potential as an anti-aging therapeutic agent. This study underscores the potential of chrysin as a natural calorie restriction mimetic, mainly by maintaining redox balance by impacting longevity pathways and metabolic health.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"188"},"PeriodicalIF":4.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of low-intensity pulsed ultrasound on muscle mass and Fndc5 mRNA expression in aged male mice.","authors":"Yoshitsugu Kojima","doi":"10.1007/s10522-025-10331-x","DOIUrl":"10.1007/s10522-025-10331-x","url":null,"abstract":"<p><p>Sarcopenia, the progressive loss of skeletal muscle mass and function with aging, is a growing public health concern. Conventional treatments such as exercise, pharmacological agents, and nutritional support offer limited efficacy, especially in older populations with reduced mobility or comorbidities. This study aimed to evaluate low-intensity pulsed ultrasound (LIPUS) as a novel, non-invasive therapeutic approach for age-related muscle atrophy. LIPUS was applied to the right hindlimbs of young (12-week), middle-aged (60-week), and aged (95-week) mice for 8 weeks. Muscle weights and mRNA expression levels were analyzed. In aged mice, LIPUS significantly increased gastrocnemius muscle mass and upregulated Fndc5 and Opa1 mRNA, genes associated with mitochondrial function and muscle regeneration. These findings suggest that LIPUS may serve as a safe, non-invasive intervention to counteract sarcopenia by promoting muscle growth and mitochondrial gene activation in aged skeletal muscle.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"187"},"PeriodicalIF":4.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the mysteries of Hutchinson-Gilford progeria syndrome: a comprehensive review of LMNA gene mutations.","authors":"Xiaoqing Zhou, Jun Song","doi":"10.1007/s10522-025-10330-y","DOIUrl":"https://doi.org/10.1007/s10522-025-10330-y","url":null,"abstract":"<p><p>Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare and fatal disorder characterized by premature aging, predominantly resulting from mutations in the LMNA gene, which lead to the accumulation of a truncated and aberrant progerin protein. This paper offers an in-depth review of the fundamental theories, epidemiology, pathological mechanisms, and treatment strategies associated with HGPS as caused by LMNA gene mutations. Furthermore, it examines the current challenges in clinical translation, with the objective of providing a comprehensive reference for research and therapeutic development in the field of HGPS.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"186"},"PeriodicalIF":4.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of physical exercise on genotoxicity in older adults: a systematic review.","authors":"Thiago Guedes Pinto, Daniel Vitor de Souza, Katia De Angelis, Ronaldo Vagner Thomatieli-Santos, Patricia Ramos Cury, Jean Nunes Dos Santos, Rogerio Aparecido Dedivitis, Daniel Araki Ribeiro","doi":"10.1007/s10522-025-10327-7","DOIUrl":"10.1007/s10522-025-10327-7","url":null,"abstract":"<p><p>In the context of increasing life expectancy, a higher prevalence of age-related chronic diseases is becoming more common in the health landscape, many of which are closely linked to insufficient physical exercise during lifespan. On the other hand, aging is also associated with damage to various molecules, including DNA, by reactive oxygen species. Given that both senescence and muscle mass loss are intimately linked to increased levels of DNA damage and deterioration of antioxidant defense, this systematic review aims to evaluate whether regular physical exercise could indeed induce genotoxicity and to assess the quality of published articles on this topic. To achieve this objective, a total of 16 selected studies were meticulously analyzed by three experienced reviewers, who assigned scores to each study based on predetermined analysis parameters. Our results revealed that there is no consensus in the literature regarding genotoxicity induced by regular physical activity in older adults, regardless of the type, volume and intensity of exercise performed. In terms of quality assessment, 11 studies (out of 16) were categorized as Strong or Moderate, thus we consider our findings to be reliable. Undoubtedly, these findings are crucial for elucidating the role of regular physical exercise on genotoxicity-related biomarkers in older adults.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"185"},"PeriodicalIF":4.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifaceted dynamics of circadian timing system influence aging and longevity.","authors":"Anita Jagota, Zeeshan Akhtar Khan, Sushree Abhidhatri Sharma, Priyanka","doi":"10.1007/s10522-025-10324-w","DOIUrl":"https://doi.org/10.1007/s10522-025-10324-w","url":null,"abstract":"<p><p>Circadian time keeping system (CTS) consisting of network of central and peripheral clocks regulates physiological, metabolic, and behavioural processes in alignment with the 24 hour. Desynchrony between central and peripheral clocks contributes to the pathogenesis of age-related conditions such as metabolic syndrome, cognitive decline, immune dysfunction, and neurodegenerative diseases etc. Sex-specific susceptibilities further modulate circadian resilience, with hormonal changes and redox imbalances playing key roles in the aging trajectory. Immune senescence and hormonal dampening, particularly in cortisol and melatonin rhythms, exacerbate circadian misalignment, accelerating systemic decline with aging. Interestingly, aging and clock dysfunction is a bidirectional process, i.e. aging progressively influences circadian rhythms across multiple levels and vice versa, from the molecular architecture of core clock gene feedback loops to the functionality of the central pacemaker-the suprachiasmatic nucleus (SCN)-and its coordination with peripheral oscillators. This review critically highlights the complex alterations in circadian mechanisms associated with aging, including diminished transcriptional rhythmicity, epigenetic drift, mitochondrial desynchronization, and disruptions in neurotransmitter systems. Such changes in turn leads to weakened SCN output, impaired photic entrainment, and loss of temporal coherence across organ systems. Further, this review demonstrates CTS and aging at multiple levels such as behavioural, physiological, biochemical and molecular levels are linked in push-pull mechanism i.e., the breakdown in the harmony of circadian rhythms at systemic level pushes the organism towards early aging and aging in turn is linked to CTS disorders.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"184"},"PeriodicalIF":4.1,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Realistic expectations for changes to average human lifespan in the near future.","authors":"Adiv A Johnson","doi":"10.1007/s10522-025-10323-x","DOIUrl":"https://doi.org/10.1007/s10522-025-10323-x","url":null,"abstract":"","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"183"},"PeriodicalIF":4.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin's role in ameliorating perturbed circadian immune molecular links with aging and sleep deprivation in central and peripheral clocks in male Wistar rats.","authors":"Zeeshan Akhtar Khan, Anita Jagota","doi":"10.1007/s10522-025-10321-z","DOIUrl":"https://doi.org/10.1007/s10522-025-10321-z","url":null,"abstract":"<p><p>Sleep deprivation (SD) and aging are linked to chronic inflammation, a contributor to age-associated diseases. Circadian rhythms, governed by suprachiasmatic nucleus (SCN), regulate immune and inflammatory responses. While aging and SD elevate pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6, their impact on temporal dynamics of inflammation across tissues and age groups remains unclear. This study examines age-dependent effects of chronic total SD on daily expression rhythms of inflammatory markers in central (SCN) and peripheral (cerebral cortex, liver, intestine) clocks of male Wistar rats aged 3 (adult), 12 (middle-aged), and 24 (old) months (m). Nitric oxide (NO), linked to inflammation and metabolism, was also evaluated in liver and intestine. Animals were sampled at four Zeitgeber (ZT) times. Further, the study examined the effects of melatonin, a circadian-regulated antioxidant, anti-inflammatory agent, and sleep synchronizer, on daily rhythms of inflammatory markers with aging and upon SD were studied. The mRNA expression levels of rTnf-α, rIl-6 and rIl-1β were assessed using qRT-PCR. NO levels were measured using Griess assay. Rats were grouped as control, SD, SD + melatonin and vehicle control groups. Significant SD-induced misalignment, especially in rIl-6 and rTnf-α in cerebral cortex and liver was observed in 12 m. SD altered circadian phases and expression levels were significantly greater in older rats (24 m > 12 m > 3 m) and in peripheral clock as compared to central clock liver > cerebral cortex > intestine > SCN. Melatonin differentially restored these rhythms, most effectively for rIl-1β and in the cerebral cortex and liver. SCN showed highest resilience, reinforcing its role as the central circadian pacemaker, while the liver and cerebral cortex emerged as the most vulnerable to SD and aging.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"181"},"PeriodicalIF":4.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of the age-related changes in the rat cerebellar cortex by using histologic and histometric methods.","authors":"Tansu Kuşat, Emrah Sur","doi":"10.1007/s10522-025-10325-9","DOIUrl":"https://doi.org/10.1007/s10522-025-10325-9","url":null,"abstract":"<p><p>Aging is characterized as a process resulting in the structural and functional deterioration of several essential organs and tissues. This study aimed to determine the effects of normal aging on the cerebellum by using histological and histometric techniques. A total of 24 male Wistar albino rats were divided into three groups: young (4-6 weeks), adult (20-22 weeks), and old (22-24 months). Cerebellar tissue samples were treated using histological and immunohistochemical techniques. The slides were evaluated using a light microscope. Molecular layer thickness was high in the adult group compared to the younger and older groups, whereas the granular layer was significantly thicker in both the adult and elderly groups than in the young rat group (P < 0.05). The total cortical thickness exhibited statistically significant differences among all age groups. The thickest cortex was observed in the adult group (P < 0.05). PAS-positive aging pigment granules were observed in the cytoplasm of Purkinje cells in older rat groups. The density of glial fibrillary acidic protein-immunoreactive (GFAP-IR) astrocytes in old rats was significantly increased compared to young and adult rats with distinct hypertrophy and strong GFAP immunoreactivity in astrocyte cell bodies. It was established that, despite age-related variations that exist, cerebellar folia height and width gradually increased from young to adult rat. In contrast, old rats have decreased cerebellar folia height and width than adults.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"182"},"PeriodicalIF":4.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}