Biogerontology最新文献

{"title":"Hyperoside extends lifespan in Caenorhabditis elegans through SEK-1/PMK-1/SKN-1 pathway.","authors":"Xin-Tian Yu, Lin Shi, Qiong Huang, Bao Li, Yan-Qing Li, Li-Lan Ou, Huai-Rong Luo, Gui-Sheng Wu","doi":"10.1007/s10522-025-10322-y","DOIUrl":"https://doi.org/10.1007/s10522-025-10322-y","url":null,"abstract":"<p><p>The progressive functional decline associated with aging is a primary risk factor for numerous chronic diseases. The discovery of natural compounds that can modulate conserved longevity pathways offers a promising strategy for promoting healthy aging. Hyperoside, a flavonoid abundant in edible plants such as hawthorn, possesses various pharmacological activities, but its specific role and molecular mechanisms in geroprotection remain poorly understood. This study aimed to elucidate the anti-aging effects of hyperoside and its underlying mechanisms using the model organism Caenorhabditis elegans (C. elegans). Our results showed that hyperoside treatment significantly extended the mean lifespan of wild-type C. elegans by up to 19.97% and robustly enhanced healthspan by improving motility and reducing the accumulation of the aging biomarker lipofuscin. Hyperoside could also alleviate Parkinsonism in neurodegeneration models, without disrupting lipid homeostasis or reproduction. Furthermore, hyperoside conferred increased resistance to thermal, oxidative, and pathogenic stress. Mechanistically, the lifespan-extending effects of hyperoside requires the transcription factors DAF-16/FOXO, SKN-1/Nrf2, and HSF-1, and factors involved in immune and anti-oxidative response, including the MAPKK SEK-1 and p38 MAPK PMK-1. Hyperoside treatment promoted the nuclear translocation of DAF-16 and SKN-1 and upregulated their respective downstream target genes, including sod-3 and gst-4. Hyperoside also increased the expression of genes that are the downstream target of both PMK-1 and SKN-1. Since the role of SKN-1 in immune and anti-oxidative response were regulated by PMK-1. Therefore, the beneficial effects of hyperoside might be mediated primarily by activating SEK-1 /PMK-1/ SKN-1 pathway, which subsequently activate HSF-1 to maintain proteostasis. These findings underscore the potential of hyperoside as a dietary-derived agent for combating age-related functional decline.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"180"},"PeriodicalIF":4.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090916","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":"Enhancing healthspan with Ashwagandha (Withania somnifera): a comprehensive review of its multifaceted geroprotective benefits.","authors":"Maanya Vittal, Manlio Vinciguerra","doi":"10.1007/s10522-025-10320-0","DOIUrl":"10.1007/s10522-025-10320-0","url":null,"abstract":"<p><p>Ashwagandha (Withania somnifera), a revered herb in Ayurvedic medicine, has gained significant scientific recognition for its potential to promote healthy aging. Traditionally used as a Rasayana or rejuvenator, this potent adaptogen helps the body manage stress and enhance vitality. This review synthesises extensive evidence for its multifaceted anti-aging capabilities, which target key hallmarks of the aging process. The mechanisms underpinning its effects include enhancing telomerase activity to support cellular longevity, combating systemic oxidative stress, and powerfully countering inflammaging by modulating immune responses and lowering inflammatory markers like C-reactive protein. Robust clinical evidence demonstrates its efficacy in improving crucial physiological parameters, including significant gains in muscle strength and size, enhanced cardiorespiratory fitness, hormonal balance, skin health, and improved sleep quality in older adults. Furthermore, trials have consistently shown its ability to improve cognitive function, including memory and information-processing speed, particularly in adults with mild cognitive impairment. Promising preclinical data also highlight its neuroprotective potential in models of Alzheimer's and Parkinson's disease. Here, we review the current evidence supports Ashwagandha's therapeutic potential in extending healthspan and enhancing quality of life. Large-scale, long-term clinical trials using standardized extracts are essential to fully confirm its role in healthy aging within the global population.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"179"},"PeriodicalIF":4.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022725","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":"Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity.","authors":"Sarah Al-Dulaimi, Ross Thomas, Sheila Matta, Terry Roberts","doi":"10.1007/s10522-025-10315-x","DOIUrl":"10.1007/s10522-025-10315-x","url":null,"abstract":"<p><p>Epitalon, a naturally occurring tetrapeptide, is known for its anti-aging effects on mammalian cells. This happens through the induction of telomerase enzyme activity, resulting in the extension of telomere length. A strong link exists between telomere length and aging-related diseases. Therefore, telomeres are considered to be one of the biomarkers of aging, and increasing or maintaining telomere length may contribute to healthy aging and longevity. Epitalon has been the subject of several anti-aging studies however, quantitative data on the biomolecular pathway leading to telomere length increase, hTERT mRNA expression, telomerase enzyme activity, and ALT activation have not been extensively studied in different cell types. In this article, the breast cancer cell lines 21NT, BT474, and normal epithelial and fibroblast cells were treated with epitalon then DNA, RNA, and proteins were extracted. qPCR and Immunofluorescence analysis demonstrated dose-dependent telomere length extension in normal cells through hTERT and telomerase upregulation. In cancer cells, significant telomere length extension also occurred through ALT (Alternative Lengthening of Telomeres) activation. Only a minor increase in ALT activity was observed in Normal cells, thereby showing that it was specific to cancer cells. Our data suggests that epitalon can extend telomere length in normal healthy mammalian cells through the upregulation of hTERT mRNA expression and telomerase enzyme activity.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"178"},"PeriodicalIF":4.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999552","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":"Role of circadian CLOCK signaling in cellular senescence.","authors":"Ziyou Yuan, Eugenie Nepovimova, Qinghua Wu, Kamil Kuca","doi":"10.1007/s10522-025-10319-7","DOIUrl":"10.1007/s10522-025-10319-7","url":null,"abstract":"<p><p>The circadian rhythm is a key biological mechanism that aligns organisms' physiological processes with Earth's 24-h light-dark cycle, crucial for cellular and tissue homeostasis. Disruption of this system is linked to accelerated aging and age-related diseases. Central to circadian regulation is the CLOCK protein, which controls gene transcription related to tissue homeostasis, cellular senescence, and DNA repair. Research reveals CLOCK's dual role: in normal cells, it supports rejuvenation by activating DNA repair factors like XPA and modulating metabolism; in tumor cells, CLOCK signaling is often hijacked by oncogenic drivers like c-MYC and Pdia3, which inhibit telomere shortening / cellular senescence, thereby fostering uncontrolled proliferation and tumorigenesis. Additionally, gut microbiota-derived aryl hydrocarbon receptor (AhR) signals can disrupt the CLOCK-BMAL1 complex, affecting circadian rhythms. CLOCK also interacts with mTOR and NF-κB pathways to regulate autophagy and mitigate harmful secretions impacting tissue function. This review examines the molecular links between CLOCK and cellular senescence, drawing from animal and human studies, to highlight CLOCK's role in aging and its potential as a target for anti-aging therapies.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"177"},"PeriodicalIF":4.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941031","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":"Realistic expectations for changes to average human lifespan in the near future.","authors":"Adiv A Johnson","doi":"10.1007/s10522-025-10318-8","DOIUrl":"10.1007/s10522-025-10318-8","url":null,"abstract":"<p><p>A recent publication presented the results of a survey given to longevity experts that attended the 2022 Systems Aging Gordon Research Conference. Corroborating results from a prior survey and broader discussions in the field, the authors found that there was little consensus on fundamental topics, including what causes aging. While this disagreement is not particularly surprising, the spread of answers to the following prompt was unexpected: \"The average lifespan in developed countries will be increased by >10 years in the next 20 years.\" On a five-point agreeability scale, a slight, significant majority of respondents indicated agreement with this projection. To get a sense of how ambitious this prediction is, a previous analysis concluded that preventing every single cancer death would only increase life expectancy at birth by around three years. Moreover, the majority of gains in life expectancy since 1900 are due to improvements in preventing and managing infectious and contagious diseases. Given all of this, the lengthy lag between discovery and translation, the time required to prepare for and launch longevity-oriented clinical trials, and the limited number of reproducible interventions that robustly extend lifespan in male and female mice, it is unlikely that 10+ year increases to average lifespan are just around the corner in developed countries. While aging is undoubtedly modifiable and further improvements in longevity are achievable, the field's optimism should not distract from what is realistically attainable and the amount of work and time required to successfully identify, test, and translate pro-longevity interventions.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"176"},"PeriodicalIF":4.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941034","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":"Early and long-term effects of maternal protein restriction on offspring organs and systems: insights from the developmental origins of health and disease (DOHaD).","authors":"Matheus Naia Fioretto, Luisa Annibal Barata, Isabelle Tenori Ribeiro, Flávia Alessandra Maciel, Renato Mattos, Patrick Vieira de Souza, Luiz Marcos Frediane Portela, Sérgio Alexandre Alcântara Dos Santos, Wellerson Rodrigo Scarano, Luis Antonio Justulin","doi":"10.1007/s10522-025-10316-w","DOIUrl":"https://doi.org/10.1007/s10522-025-10316-w","url":null,"abstract":"<p><p>Maternal malnutrition affects millions of people worldwide in two main ways: through food insecurity and hunger, as well as through diets high in ultra-processed, low-nutrient foods. These effects are often linked to deficiencies in specific macronutrients and micronutrients, which can lead to organ-specific consequences in the biological development of the child-a context explored within the framework of the Developmental Origins of Health and Disease (DOHaD). Given the extensive effects of maternal protein restriction (MPR) on offspring development, this review focuses specifically on low-protein diets and their impact on various organs and systems. It compiles both experimental and epidemiological data across different developmental stages. Poor maternal nutrition can impair embryonic and fetal development, creating a stressful microenvironment for both mother and child from the earliest stages of life. This stress can leave epigenetic marks that influence health and disease outcomes later in life. Numerous studies have documented the wide-ranging consequences of malnutrition, highlighting its detrimental effects on metabolic, molecular, and phenotypic systems. This narrative review aims to present both the immediate and long-term effects of exposure to MPR throughout the lifespan of the offspring.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"175"},"PeriodicalIF":4.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940846","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":"Genetic influence of the brain on epigenetic age acceleration: evidence of a large-scale genetic correlation study.","authors":"Chengcheng Li, Jiaze Tang, Junshuan Cui, Niya Long, Wu Cen, Qibo Wu, Ming Yang, Liangzhao Chu, Xingwang Zhou","doi":"10.1007/s10522-025-10314-y","DOIUrl":"https://doi.org/10.1007/s10522-025-10314-y","url":null,"abstract":"<p><p>The relationship between the brain and aging remains unclear. Our objective is to explore the causal connections between brain structure,gene expression, and traits associated with aging. Mendelian randomization(MR) analysis was conducted to explore the associations between brain structures and aging-related traits including GrimAge acceleration(GrimAA), PhenoAge acceleration (PhenoAA), HannumAge acceleration(HannumAA), HorvathAge acceleration(HorvathAA), and leukocyte telomere length(LTL). The Linkage Disequilibrium Score Regression(LDSC) method was employed to identify the shared genetic etiology between brain structures and aging. The Summary Data-based Mendelian Randomization(SMR) was utilized to investigate which brain genes have a causal influence on aging. We also examined the expression of the 8 genes derived from the SMR analysis across different cell types in post-mortem human brain specimens. The phenotypes potentially linked to genetics, as indicated by the LDSC outcomes, are as follows:148 phenotypes with GrimAA,150 phenotypes with HannumAA, 160 phenotypes with HorvathAA, 160 phenotypes with PhenoAA,and 110 phenotypes with LTL. Concerning the causal link between brain structures and aging-related traits, 7 brain structures consistently demonstrated a causative effect on GrimAA, while 29 brain structures exerted a causal influence on PhenoAA.Additionally, 7 BIDs revealed a causal relationship with HannumAA. There are 10 and 14 brain structures have a causative effect on HorvathAA and LTL, respectively. SMR revealed that 8 genes(CCDC144B, SHMT1, FAM106A, FAIM, CTD-2303H24.2, EBAG9P1, USP32P2 and OGFOD3) expression in different brain regions affected aging. These genes exhibit different expression patterns in various cells. Our results are in line with the possibility of a causal connection between aging and brain structure.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"174"},"PeriodicalIF":4.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940926","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 interplay between circadian rhythms and aging: molecular mechanisms and therapeutic strategies.","authors":"Prashant Dhaka, Neha, Risabh Kumar, Chowdhury Mobaswar Hossain, Suhel Parvez","doi":"10.1007/s10522-025-10301-3","DOIUrl":"https://doi.org/10.1007/s10522-025-10301-3","url":null,"abstract":"<p><p>Circadian rhythms are essential biological systems operating on a 24-h cycle, playing a crucial role in regulating sleep, cognitive function, immune responses, and hormone secretion. This review explores the intricate relationship between circadian rhythms and aging, with a focus on the underlying molecular mechanisms. It discusses age-related changes in sleep patterns and the role of circadian disruption in the progression of neurodegenerative diseases such as Parkinson's and Alzheimer's. Special attention is given to the core CLOCK genes, including BMAL1 and Per2, and their regulatory influence on these processes. The review also highlights the impact of circadian misalignment on metabolic disorders, particularly obesity, diabetes, and cardiovascular disease. Emerging therapeutic strategies targeting circadian pathways-ranging from pharmacological agents to lifestyle modifications-are presented as promising approaches to support healthy aging. This review provides the deeper understanding of how aging affects circadian regulation may pave the way for targeted interventions aimed at extending lifespan and enhancing overall quality of life.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"173"},"PeriodicalIF":4.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941077","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":"Zuogui and Yougui pills extend lifespan and improve ageing biomarkers via kaempferol-mediated mitophagy in Caenorhabditis elegans.","authors":"Wendi Chen, Shuang Liu, Guoqiang Xu, Xin Liu, Yuxuan Shi, Guolong Wang, Yunna Ning, Zhiming Lu, Yongzhi Cao, Yueran Zhao","doi":"10.1007/s10522-025-10317-9","DOIUrl":"https://doi.org/10.1007/s10522-025-10317-9","url":null,"abstract":"<p><p>Zuogui pill (ZGP) and Yougui pill (YGP) are classical kidney-tonifying formulas in Traditional Chinese Medicine, widely used clinically but with their potential to delay ageing and improve ageing biomarkers remaining unclear. This study combined network pharmacology and Caenorhabditis elegans models to investigate the anti-ageing effects and mechanisms of ZGP and YGP. Both formulas significantly extended lifespan (ZGP dose-dependently at 5-20 mg/mL; YGP at 20 mg/mL) and improved ageing biomarkers, as evidenced by enhanced motility, reduced lipofuscin accumulation and endogenous ROS levels, and increased resistance to heat and oxidative stress. Network analysis identified quercetin and kaempferol as the top-ranked shared active components. Subsequent experimental validation demonstrated that kaempferol (0.05-0.2 mM) replicated these pro-longevity effects and was shown to act by inducing mitophagy: it triggered an initial decrease followed by a long-term increase in mitochondrial content, concomitant with upregulated expression of mitophagy genes. Crucially, the lifespan-extending effects of kaempferol, ZGP, and YGP were completely abolished in bec-1 and pink-1 null mutants. This study establishes that ZGP and YGP delay ageing and improve ageing biomarkers in C. elegans by activating BEC-1/PINK-1-dependent mitophagy. Kaempferol was identified as a major active component mediating this effect, highlighting a key mechanism for the pro-longevity properties of these traditional formulas.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"172"},"PeriodicalIF":4.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941037","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":"Blueberries for brainpower: A systematic review and meta-analysis with Bayesian post hoc analysis of RCTS exploring cognitive function in the elderly with prior cognitive decline.","authors":"Ana Beatriz Nardelli da Silva, Gabriel Moraes de Oliveira, Mariano Gallo Ruelas, Maitê Silva Martins Gadelha, Ana Clara Felix de Farias Santos, Fernanda Valeriano Zamora","doi":"10.1007/s10522-025-10308-w","DOIUrl":"https://doi.org/10.1007/s10522-025-10308-w","url":null,"abstract":"<p><p>Blueberries are anthocyanin-rich fruits widely consumed by the general population, with well-established health benefits on the endocrine and cardiovascular systems attributed to their potent anti-inflammatory properties. However, the potential impact of blueberry consumption on cognitive function in elderly individuals with prior cognitive decline, such as Alzheimer's disease and dementia, remains insufficiently explored in the literature. Therefore, we aimed to evaluate the potential effects of chronic blueberry consumption on cognitive performance in this population through various memory assessment tools. We searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) evaluating the effect of chronic blueberry consumption on cognitive function. We pooled standard mean differences (SMD) and 95% confidence interval (CI) using a random-effects model. We identified nine eligible RCTs involving 513 patients. In elderly individuals with mild cognitive impairment (MCI) and subjective cognitive decline, blueberry intake showed a statistically significant improvement in episodic memory. (SMD = 0.34; 95% CI 0.11 to 0.57; p < 0.05). The subgroup analysis revealed that diagnostic objetivity was not a statistically significant effect modifier. Blueberry intake was also associated with improved language memory in MCI patients (SMD = 0.30; 95% CI 0.01 to 0.60; p < 0.05). No improvements were seen in processing speed (SMD = - 0.33; 95% CI - 0.85 to 0.19, p > 0.05), recognition memory (SMD = 0.14; 95% CI - 0.17 to 0.46, p > 0.05), visuospatial learning (SMD = 0.32; 95% CI - 0.16 to 0.79, p > 0.05) and working memory (SMD = 0.09; 95% CI - 0.21 to 0.39, p > 0.05). Chronic blueberry intake may improve episodic memory in the elderly with MCI and subjective cognitive decline, and also language in the elderly with MCI. These findings should be confirmed in further multicenter trials to confirm generalizability and long-term impact.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 5","pages":"171"},"PeriodicalIF":4.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940834","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}