Biogerontology最新文献

{"title":"A gain-of-function screening reveals dAnkmy2 as a potential mediator of lifespan extension and oxidative stress resistance in Drosophila melanogaster.","authors":"Manabu Tsuda, Toru Togawa, Mihoko Akita-Tanaka, Takashi Matsuo, Toshiro Aigaki","doi":"10.1007/s10522-026-10441-0","DOIUrl":"https://doi.org/10.1007/s10522-026-10441-0","url":null,"abstract":"<p><p>Gain-of-function screening in Drosophila melanogaster provides a powerful approach for identifying genes that modulate lifespan; however, induction strength and environmental stress can substantially influence phenotypic outcomes. Here, we performed a pilot Gene Search (GS)-based overexpression screen using a heat-inducible hs-GAL4 driver and compared lifespan analyses at 25 °C and 30 °C to evaluate the impact of induction conditions on the detectability of lifespan-modulating genes. Induction at 30 °C caused uniformly shortened lifespans across genotypes and did not reveal robust lifespan-extending candidates. In contrast, screening at 25 °C, where moderate hs-GAL4 induction produces robust and detectable transgene expression, revealed multiple longevity-promoting lines. Lifespan measurements at the two temperatures were poorly correlated, indicating that elevated temperature imposes a dominant physiological burden that masks gene-specific effects. Using this strategy, we characterized a candidate line overexpressing Drosophila Ankyrin repeat and MYND domain-containing protein 2 (dAnkmy2). Overexpression of dAnkmy2 significantly extended adult lifespan and enhanced resistance to oxidative stress without detectable changes in canonical antioxidant gene expression. In contrast, loss of dAnkmy2 caused larval lethality, indicating an essential developmental function. Given the conserved role of Ankmy2 in ciliary biology, our results raise the possibility that cilia-associated processes may be involved in lifespan regulation. Collectively, this study establishes a proof-of-principle framework for detecting subtle genetic modulators of aging in genetically robust systems.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761073","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":"Shenrong Guben Huanshao Pill enhanced stress resistance and extended the lifespan of Caenorhabditis elegans by activating the oxidative stress system via the DAF-16/FOXO signaling pathway.","authors":"Yi-Nan Yang, Xin Wang, Hong-Fen Jiang, Jie Yang, Subiy Akbara, Xiao-Qin Yang, Hai-Qing Fan, Guo-Lin Chai, Dong-Qing Fei, Fang-Di Hu, Shuang-Xi Qian, Zhan-Xin Zhang","doi":"10.1007/s10522-026-10439-8","DOIUrl":"https://doi.org/10.1007/s10522-026-10439-8","url":null,"abstract":"<p><p>SRGBHSP is a classic traditional Chinese medicinal. Modern studies found that SRGBHSP had antioxidant, anti-inflammatory and constitution-strengthening pharmacological effects. Oxidative stress is a major factor that can cause an organism to age. Therefore, we proposed that SRGBHSP has an aging modulatory effect by its antioxidant properties. In the present study, we used a C. elegans model to explore the aging modulatory activity of the extract from SRGBHSP. Aging modulatory effects of SRGBHSP were determined by lifespan assays under normal and extreme conditions, as well as assays for body bending frequency and pharyngeal pumping rate. In vivo antioxidant activity of SRGBHSP was estimated through ROS, MDA levels and the activities of antioxidant enzymes. The mechanisms of aging modulatory effects of SRGBHSP were further investigated via qRT-PCR, nuclear translocation assay, transcriptomics and metabolomics analysis. SRGBHSP extends the lifespan of C. elegans and reduces the accumulation of oxidative metabolites. SRGBHSP upregulated the transcription of daf-16, promoted the nuclear translocation of DAF-16 and increased the transcription of downstream genes sod-3 and gst-4. KEGG enrichment analysis of the transcriptome identified the peroxisome pathway and the classical DAF-16/FOXO-dependent IIS longevity pathway. Metabolomics indicates that SRGBHSP primarily exerts its function by affecting the vitamin B6 metabolic pathway. The results of this study showed that SRGBHSP increased the activity of antioxidant enzyme in C. elegans and reduced the products of oxidative metabolism to prevent oxidative stress. Its aging modulatory effect is mainly produced through the activation of DAF-16/FOXO-dependent IIS signaling pathway and vitamin B6 metabolic pathway.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761071","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: From sick care to healthspan: educating the longevity physician for health maintenance and health promotion.","authors":"Dominik Thor, David Barzilai, Yu-Xuan Lyu, Luiza Spiru","doi":"10.1007/s10522-026-10433-0","DOIUrl":"https://doi.org/10.1007/s10522-026-10433-0","url":null,"abstract":"","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761137","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":"Gut microbiota as potential mediator linking dietary preferences and aging phenotypes.","authors":"Weidong Li, Xueyao Cai, Yuchen Cai, Jianda Zhou","doi":"10.1007/s10522-026-10437-w","DOIUrl":"https://doi.org/10.1007/s10522-026-10437-w","url":null,"abstract":"<p><p>Aging is a complex process influenced by various factors, including gut microbiota and food likings. Focusing on gut and dietary health is a crucial strategy for promoting long-term health and active aging. This study investigates the reciprocal causal relationships between gut microbiota, food likings and aging using Mendelian Randomization (MR) approaches. We leveraged the summary statistics of gut microbiota (n = 5,959), food likings (n = 161,625), and three aging phenotypes including telomere length (n = 472,174), facial aging (n = 423,999), and frailty index (n = 175,226). We performed bidirectional MR analyses to explore the causal effects of gut microbiota and food likings on aging, and mediation analyses to discover potential mediating gut microbiota and food likings. We discovered numerous correlations between gut microbiota, food likings, and aging. Notably, we identified that Lachnospira rogosae and CAG-83 sp000435555 influenced the frailty index through diet fizzy drinks liking, while UBA2922 sp900313925 had an effect through F-wine liking. Our findings provide insights into these complex interactions and offer a basis for personalized dietary interventions to slow aging and improve health, potentially informing new strategies for preventing age-related diseases.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761086","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 neuroprotective effect of Cucurbitacin B against Aβ and tau toxicities requires functional HDAC6 and stress granule pathways.","authors":"Xiaohui Tu, Minglv Fang, Yingxuan Yan, Ying Liu, Jing Yu, Liang Chen, Lu Zhang, Cheng Huang, Shengjie Fan","doi":"10.1007/s10522-026-10426-z","DOIUrl":"https://doi.org/10.1007/s10522-026-10426-z","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by proteostasis collapse driven by amyloid-β (Aβ) plaques and tau tangles. Dysregulation of stress granule (SG) dynamics and aberrant histone deacetylase 6 (HDAC6) activity are emerging as pivotal pathogenic mechanisms promoting neurodegeneration. Here, we identify that Cucurbitacin B (CB), a natural triterpenoid, acts as a potent SG inducer that confers broad-spectrum neuroprotection. Mechanistically, we demonstrate a novel \"recruit-and-sequester\" model: CB promotes the assembly of HDAC6-recuited SGs, thereby physically sequestering HDAC6 and functionally inhibiting its deacetylase activity. In Caenorhabditis elegans (C. elegans) and mammalian cell models, CB treatment significantly alleviated Aβ oligomer-induced cytotoxicity and tau hyperphosphorylation. Notably, the neuroprotective efficacy of CB was abolished by the genetic knockdown of core SG components (gtbp-1/G3BP1, tiar-1/TIA1) or hda-6/HDAC6, confirming that its therapeutic action relies on the integrity of the HDAC6-SG. Our findings highlight the potential of modulating SG dynamics to spatially regulate HDAC6, offering a novel therapeutic strategy for AD.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761151","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":"Ageing was never a singular problem in biology: implications for mechanisms, measurements and interventions.","authors":"Piotr Paweł Chmielewski","doi":"10.1007/s10522-026-10436-x","DOIUrl":"10.1007/s10522-026-10436-x","url":null,"abstract":"<p><p>Biological ageing is often approached through its underlying mechanisms and their therapeutic potential. Yet age-related decline arises from multiple processes shaped by evolutionary constraints and finite investment in somatic maintenance. Coupling among these processes is heterogeneous: some are tightly linked through shared signalling networks, others are indirectly related and some retain substantial autonomy. Interventions that modulate biomarkers of biological age or individual hallmarks typically produce partial, tissue-selective effects rather than uniform reversal of ageing in humans. This pattern is more consistent with a distributed network of partially independent processes with key nodes of regulatory integration than with a single upstream mechanism. Because molecular, cellular, tissue and organismal levels retain partial autonomy, human ageing can be viewed as a multilevel phenomenon. Geroscience may therefore advance by mapping this network and identifying interventions that target central regulatory hubs and affect multiple downstream processes, thereby preserving function, extending healthspan and reducing the burden of ageing.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728253","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":"Lycium barbarum polysaccharides promote longevity and healthspan in Caenorhabditis elegans via insulin/IGF-1 signalling and lipid metabolic remodelling.","authors":"Linzhen Chen, Zhuo Yang, Xiaolu Chen, Qi Chen, Juhui Hao, Zhiqiang Ma","doi":"10.1007/s10522-026-10435-y","DOIUrl":"10.1007/s10522-026-10435-y","url":null,"abstract":"<p><p>Lycium barbarum (goji berry) has long been consumed as a food, and its water-soluble polysaccharides (LBPs) are proposed as key bioactive constituents. Here, we evaluated three L. barbarum fractions in Caenorhabditis elegans and subsequently focused on purified LBPs, which showed the most consistent pro-longevity phenotype in preliminary screening. LBPs (700 μg/mL) increased mean lifespan by 20.67% (p < 0.01) and improved multiple healthspan-related outcomes, including locomotion, resistance to heat and oxidative stress, and reduced age-associated accumulation of lipofuscin and neutral lipids. Using mutant and transgenic strains, we found that these benefits depend on the transcription factors DAF-16/FOXO, SKN-1/Nrf2 and HSF-1, and are attenuated in an insulin/IGF-1 signalling (IIS) pathway mutant (age-1/PI3K). Consistent with altered lipid homeostasis, LBPs changed the expression of lipid metabolic genes, including Δ9 desaturases (fat-6/fat-7) and fat-5. Collectively, these findings indicate that LBPs can promote longevity and functional maintenance in C. elegans, with effects linked to IIS, stress-response regulation and lipid metabolic remodeling.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728199","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":"Dietary unsaturated fatty acids distinctly associate with the early age sleep-wake cycle and gut integrity in aged fruit flies, Drosophila melanogaster.","authors":"Aradhana Joshi, Pooja Ramakrishnan, Mohamed Fazil, Ponnalagu Lakshmanan, Pankaj Yadav","doi":"10.1007/s10522-026-10434-z","DOIUrl":"https://doi.org/10.1007/s10522-026-10434-z","url":null,"abstract":"<p><p>Obesity is a risk factor for compromised health and a driver for non-communicable diseases. Effects of various fats on health, behavior, and other parameters have been studied using different model organisms, including fruit flies Drosophila melanogaster, by exposing them to dietary fats (saturated and trans fatty acids). However, the long-term and short-term effects of dietary unsaturated fatty acids (USFA) on physiology and sleep-activity behavior are relatively less explored. Hence, the present study hypothesizes that exposure to a USFA-rich diet differentially influences early-life behavioral traits and long-term fitness in fruit flies. The results of our study reveal that the flies exhibit attraction to USFA, with comparable responses to control and the higher doses. We further observed sexual dimorphism in lifespan, with males fed with low-dose (2.5%) and intermediate-dose (10%) USFA outliving females. Further, upon first-time examining the interaction between behavioral changes and fitness of flies fed with USFA, our results reveal that the females under MUFA increased late-night activity, and the female flies fed highest dose of MUFA (20%) exhibited sleep reorganization, by reduced sleep in nighttime and increased in daytime. Further, MUFA-fed flies enhance sleep fragmentation at an early age. In line at late age, flies fed with an intermediate dose of MUFA showed loose gut integrity (Smurf positive). Overall, this study suggests that USFA-fed flies have shorter survival associated with sleep fragmentation in early life and reduced gut integrity of flies at a late age in a sex and dose-dependent manner. Highlighting sleep fragmentation and gut dysfunction may contribute dietary USFA quality to aging-associated fitness.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697415","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":"Mucuna pruriens mitigates aging-related testicular dysfunction and sperm parameters by restoring cell adhesion molecules and junctional complexes.","authors":"Mohammad Zafar Iqbal Khan, Prakash Seppan","doi":"10.1007/s10522-026-10432-1","DOIUrl":"https://doi.org/10.1007/s10522-026-10432-1","url":null,"abstract":"<p><p>Aging is associated with progressive testicular dysfunction, including disruption of the blood-testis barrier (BTB), loss of junctional proteins, impaired spermatogenesis, and reduced fertility. This study examined the therapeutic effects of Mucuna pruriens (M. pruriens), a leguminous plant with potent antioxidant and anti-inflammatory properties, on age-related degeneration of testicular junctional molecules in male Wistar albino rats. Adult (4-5 months) and aged (20-22 months) rats were divided into M. pruriens-treated and untreated groups, with 6 animals in each group. The treatment groups received a dose of M. pruriens seed extract (gavage) of 200 mg/Kg body weight for an experimental period of 45 d. Testicular tissues were analyzed via histology, Western blotting, and immunofluorescence to assess BTB protein expression, while epididymal sperm were evaluated for count, motility, viability, and membrane integrity. Results showed that aging causes a significant decrease in BTB proteins, including claudin-1, E-cadherin, N-cadherin, β-catenin, and zonula occludens-1 (ZO-1), along with disrupted seminiferous tubules, thinning of the epithelium, increased interstitial spaces, Sertoli cell vacuolization, and germ cell loss. However, M. pruriens-treated rats showed increased expression of the mentioned BTB proteins. In treated aged rats, the anti-inflammatory cytokine TGF-β emerged as a senescence marker, whereas IL-10 levels mirrored those of IL-6. Pro-inflammatory markers TNFα and IL-1β decreased in the M. pruriens-treated groups. At the same time, MIF, AR and ERα expression increased in the aged rats treated with M. pruriens, indicating recovery of the testicular microenvironment. Functionally, aged rats experienced notable reductions in sperm count, viability, motility, and membrane integrity. Conversely, M. pruriens-treated aged rats displayed a marked restoration of BTB protein levels and proper localization at Sertoli-Sertoli and Sertoli-germ cell junctions. Histological analysis showed improved seminiferous structures, fewer interstitial gaps, a thicker germinal epithelium, and increased spermatozoa. M. pruriens treatment significantly enhanced sperm parameters in aged rat testes. These findings demonstrate that M. pruriens supplementation can reduce age-related testicular degeneration by restoring junctional protein expression, maintaining BTB integrity, and supporting spermatogenesis.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697455","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":"Salidroside ameliorates skin aging in male mice by promoting collagen regeneration via modulation of FOS and MMP9.","authors":"Zheng Wang, Xiaoyue Yan, Xiaofeng Li, Hongzheng Zhu, Yuan Wang, Xiaofeng Fan, Xinyu Lu, Xiaoman Li, Miao Yang, Chi Zhang, Yuanyuan Wu","doi":"10.1007/s10522-026-10430-3","DOIUrl":"https://doi.org/10.1007/s10522-026-10430-3","url":null,"abstract":"<p><p>Salidroside, a phenolic compound derived from Rhodiola rosea L., has been widely utilized in cosmetics and medicine for its anti-melanogenic properties. However, its role in collagen regeneration during skin aging remains unclear. In this study, we investigated the effects of salidroside on collagen synthesis and explored its underlying mechanisms in a murine model of skin aging. Administering salidroside (20, 40, and 80 mg/kg) orally for 28 days significantly increased dermal thickness, collagen volume, and the expression of collagen I and III in male mouse skin. Bioinformatic analysis of RNA-seq data from the GSE278079 dataset revealed enhanced neutrophil infiltration in aged skin, suggesting a role for inflammatory processes in skin aging. Furthermore, salidroside up-regulated the expression of the transcription factor FOS and down-regulated matrix metalloproteinase MMP9, both in vivo and in L929 fibroblasts. These changes correlated with reduced collagen degradation and enhanced fibroblast activity. Crucially, siRNA-mediated silencing of Fos in vitro partially diminished the salidroside-induced upregulation of collagen expression, substantiating a causal regulatory role for FOS in this process. Our results demonstrate that salidroside promotes collagen regeneration and mitigates skin aging, which is closely associated with the attenuation of neutrophil-mediated inflammation, alongside the upregulation of FOS and downregulation of MMP9. These findings highlight the therapeutic potential of salidroside in combating age-related skin changes.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643828","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}