Aging Cell最新文献

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Experimental Evidence Against Taurine Deficiency as a Driver of Aging in Humans 牛磺酸缺乏是人类衰老驱动因素的实验证据
IF 7.1 1区 医学
Aging Cell Pub Date : 2025-08-11 DOI: 10.1111/acel.70191
Vincent Marcangeli, Marina Cefis, Rami Hammad, Jordan Granet, Jean-Philippe Leduc-Gaudet, Pierrette Gaudreau, Mylène Aubertin-Leheudre, Marc Bélanger, Richard Robitaille, José A. Morais, Gilles Gouspillou
{"title":"Experimental Evidence Against Taurine Deficiency as a Driver of Aging in Humans","authors":"Vincent Marcangeli,&nbsp;Marina Cefis,&nbsp;Rami Hammad,&nbsp;Jordan Granet,&nbsp;Jean-Philippe Leduc-Gaudet,&nbsp;Pierrette Gaudreau,&nbsp;Mylène Aubertin-Leheudre,&nbsp;Marc Bélanger,&nbsp;Richard Robitaille,&nbsp;José A. Morais,&nbsp;Gilles Gouspillou","doi":"10.1111/acel.70191","DOIUrl":"https://doi.org/10.1111/acel.70191","url":null,"abstract":"<p>Taurine deficiency was recently proposed as a driver of aging in various species, including humans. To test this hypothesis, we assessed whether circulating taurine was associated with aging and physical performance in 137 physically inactive and physically active men aged 20–93. No association between circulating taurine levels and age, muscle mass, strength, physical performance, or mitochondrial function was observed, thereby challenging the implication of taurine deficiency as a primary driver of aging in humans.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 10","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oxytocin Enhances Demethylation Through TET Enzyme Expression in Neurons of Aged Mice: Oxytocin as a Potential Antiaging Peptide 催产素通过TET酶在老年小鼠神经元中的表达促进去甲基化:催产素是一种潜在的抗衰老肽。
IF 7.1 1区 医学
Aging Cell Pub Date : 2025-08-11 DOI: 10.1111/acel.70198
Yuko Maejima, Shoko Yokota, Megumi Yamachi, Shizu Hidema, Tomoyuki Ono, Shu Taira, Katsuhiko Nishimori, Heidi de Wet, Kenju Shimomura
{"title":"Oxytocin Enhances Demethylation Through TET Enzyme Expression in Neurons of Aged Mice: Oxytocin as a Potential Antiaging Peptide","authors":"Yuko Maejima,&nbsp;Shoko Yokota,&nbsp;Megumi Yamachi,&nbsp;Shizu Hidema,&nbsp;Tomoyuki Ono,&nbsp;Shu Taira,&nbsp;Katsuhiko Nishimori,&nbsp;Heidi de Wet,&nbsp;Kenju Shimomura","doi":"10.1111/acel.70198","DOIUrl":"10.1111/acel.70198","url":null,"abstract":"<p>While it is well-documented that plasma oxytocin (OXT) levels decline with age, the underlying mechanisms remain elusive. This study aimed to elucidate the physiological mechanisms contributing to this age-related decrease in plasma OXT and the possible use of OXT supplementation on improving age-related decline of neural function. Comparing young (9 weeks) and aged (&gt; 45 weeks) mice, aged mice showed reduced plasma OXT levels, an increase in the inflammation marker hs-CRP, and decreased OXT-positive neurons in the hypothalamus. Aged mice showed signs of epigenetic changes in the hypothalamus as indicated by decreased ten-eleven translocation (TET) family mRNA expression, decreased 5-hydroxymethylcytosine (5hmC) positive neurons, and downregulated mitochondrial respiratory complex IV (COX IV) expression. Nasal application of OXT (10 μg/day) for 10 days to aged mice resulted in normalized plasma OXT and inflammation levels and a recovery of OXT-positive neurons, TET2 mRNA levels, 5hmC positive neurons, and COX IV expression. Directly confirming a role for OXTR signaling, TET2, COX IV, and 5hmC in the hypothalamus and hippocampus were also found to be decreased in oxytocin receptor (OXTR) null mice, compared with age-matched WT mice. Furthermore, we show that methylation as a result of aging decreases OXT production in hypothalamic neurons, thereby reducing circulating plasma OXT levels, which can be reversed by nasal OXT treatment. The data presented here suggest that aging, DNA methylation, mitochondrial dysfunction, inflammation, and senescence are interconnected in a vicious cycle, which can be successfully interrupted by OXT treatment.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 10","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Associations of Skin Biomechanical Properties With Biological Aging Clocks and Longitudinal Changes in Intrinsic Capacity in Adults Aged 20–93: The INSPIRE-T Project 20-93岁成人皮肤生物力学特性与生物衰老时钟和内在能力纵向变化的关联:INSPIRE-T项目。
IF 7.1 1区 医学
Aging Cell Pub Date : 2025-08-10 DOI: 10.1111/acel.70190
Wan-Hsuan Lu, Sophie Guyonnet, Jérémy Raffin, Sandrine Bessou-Touya, Katia Ravard Helffer, Pascale Bianchi, Jimmy Le Digabel, Paul Bensadoun, Jean-Marc Lemaitre, Philipe de Souto Barreto, Bruno Vellas, the IHU HealthAge INSPIRE/Open Science study group
{"title":"Associations of Skin Biomechanical Properties With Biological Aging Clocks and Longitudinal Changes in Intrinsic Capacity in Adults Aged 20–93: The INSPIRE-T Project","authors":"Wan-Hsuan Lu,&nbsp;Sophie Guyonnet,&nbsp;Jérémy Raffin,&nbsp;Sandrine Bessou-Touya,&nbsp;Katia Ravard Helffer,&nbsp;Pascale Bianchi,&nbsp;Jimmy Le Digabel,&nbsp;Paul Bensadoun,&nbsp;Jean-Marc Lemaitre,&nbsp;Philipe de Souto Barreto,&nbsp;Bruno Vellas,&nbsp;the IHU HealthAge INSPIRE/Open Science study group","doi":"10.1111/acel.70190","DOIUrl":"10.1111/acel.70190","url":null,"abstract":"<p>Evidence connecting skin aging to functional decline and systemic aging biomarkers is lacking. This study investigated how skin-aging biomechanics were associated with changes in intrinsic capacity (IC), a marker of healthy aging. We also explored their links with biological aging clocks (epigenetic and inflammatory clocks) and potential moderating effects on the skin-IC relationship. Baseline skin elasticity and viscoelasticity were measured in 441 INSPIRE-T participants aged 20 to 93 (59.9% women) using Cutometer parameters. IC was evaluated over 3 years as a five-domain score covering cognition, locomotion, psychology, vitality, and sensory (a higher score indicated better). Biological aging was measured at baseline using six epigenetic clocks (Horvath pan-tissue, Horvath skin &amp; blood, Hannum, PhenoAge, GrimAge, and DunedinPACE) and inflammatory clock (iAge). Poor skin elasticity and viscoelasticity in older adults were associated with lower baseline IC after controlling for demographic, medical, and lifestyle factors. Longitudinally, older men with a higher viscoelastic ratio (R6) experienced a faster decline in IC (a standardized coefficient [95% CI] ranged from −0.37 [−0.72, −0.03] at age 62 to −1.32 [−1.91, −0.73] at age 93). Accelerated iAge was associated with reduced skin elasticity (R2, R5, R7). Moreover, the association between parameters related to elastic recovery (R5, R7) and baseline IC became more pronounced as accelerated iAge increased. This is the first study demonstrating the association between skin-aging biomechanics and IC. Poor skin elasticity was associated with higher systemic inflammation. Therefore, skin biomechanical properties may reflect overall functional aging, with inflammation serving as a common underlying factor.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 10","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Superoxide Activates Ferroptosis via the Haber-Weiss Reaction and Enhances Age-Related Macular Degeneration 超氧化物通过Haber-Weiss反应激活铁下垂并增强年龄相关性黄斑变性。
IF 7.1 1区 医学
Aging Cell Pub Date : 2025-08-10 DOI: 10.1111/acel.70195
Ying Huang, Zhenxing Zhou, Mengjia Huan, Qi Guo, Xiaoqian Zhang, Ruiqi Lu, Lushu Chen, Xiumiao Li, Jin Yao, Qin Jiang, Yong Xu
{"title":"Superoxide Activates Ferroptosis via the Haber-Weiss Reaction and Enhances Age-Related Macular Degeneration","authors":"Ying Huang,&nbsp;Zhenxing Zhou,&nbsp;Mengjia Huan,&nbsp;Qi Guo,&nbsp;Xiaoqian Zhang,&nbsp;Ruiqi Lu,&nbsp;Lushu Chen,&nbsp;Xiumiao Li,&nbsp;Jin Yao,&nbsp;Qin Jiang,&nbsp;Yong Xu","doi":"10.1111/acel.70195","DOIUrl":"10.1111/acel.70195","url":null,"abstract":"<p>Antioxidant decline is crucial to driving age-related macular degeneration (AMD). Ferroptosis, a regulated cell death mediated by iron-dependent hydroxyl radical-catalyzed phospholipid peroxidation through the Fenton reaction, is implicated in various chronic degenerative diseases. Here, we show that superoxide activates ferroptosis in retinal pigment epithelium (RPE) cells via the Haber-Weiss reaction, thereby contributing to dry AMD. We silenced manganese superoxide dismutase (MnSOD/SOD2) in RPE cells and exposed the cells to blue light to induce ferroptosis by increasing superoxide anions. Additionally, MnSOD deficiency triggered the Hsp70-linked ubiquitin-dependent degradation of GPX4, further aggravating ferroptosis. We validated blue light-induced ferroptosis in the RPE layer as a driver of the dry AMD phenotype in <i>Sod2</i><sup><i>+/−</i></sup> mice. Consequently, SOD mimetics efficiently protected RPE against phototoxicity by reducing superoxide-activated ferroptosis. Iron chelators or overexpressing GPX4 sufficiently eradicated ferroptosis. The finding reveals that excessive superoxide contributes to phospholipid peroxidation, providing a promising approach for preventing dry AMD by elevating MnSOD to inhibit RPE cell ferroptosis.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 10","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Metabolite Score of Unintentional Weight Loss Explained a Substantial Proportion of Associated Mortality and Mobility Limitation Risk in a Biracial Older Cohort 非故意体重减轻的代谢物评分解释了双种族老年队列中相当大比例的相关死亡率和活动受限风险。
IF 7.1 1区 医学
Aging Cell Pub Date : 2025-08-06 DOI: 10.1111/acel.70181
Shanshan Yao, Megan M. Marron, Samaneh Farsijani, Iva Miljkovic, George C. Tseng, Ravi V. Shah, Venkatesh L. Murthy, Anne B. Newman
{"title":"A Metabolite Score of Unintentional Weight Loss Explained a Substantial Proportion of Associated Mortality and Mobility Limitation Risk in a Biracial Older Cohort","authors":"Shanshan Yao,&nbsp;Megan M. Marron,&nbsp;Samaneh Farsijani,&nbsp;Iva Miljkovic,&nbsp;George C. Tseng,&nbsp;Ravi V. Shah,&nbsp;Venkatesh L. Murthy,&nbsp;Anne B. Newman","doi":"10.1111/acel.70181","DOIUrl":"10.1111/acel.70181","url":null,"abstract":"<p>Unintentional weight loss (UWL) is related to mortality and mobility limitation. Here, we aimed to develop a metabolite-based score for UWL and evaluate its prediction performance and explanation value for UWL-related health outcomes. Participants from the Health, Aging and Body Composition (Health ABC) study with available metabolomics and valid follow-ups were included (<i>N</i> = 2286). First, in the derivation group (<i>N</i> = 1200), 27 of the 77 metabolites associated with incident UWL (&gt; 3% annual UWL vs. weight stable) were selected by LASSO-logistic regression. The UWL metabolite score was calculated as a weighted sum of these 27 standardized metabolites, with higher scores indicating greater UWL risk. We then examined the standardized UWL metabolite score against all-cause mortality and incident mobility limitation using Cox regression. Overall, older adults with a one-SD higher UWL metabolite score had higher risks for mortality (1.44 [1.36, 1.52]) and mobility limitation (1.23 [1.15, 1.32]). The score also improved mortality prediction beyond traditional risk factors. Similar results were observed in the hold-out test group (<i>n</i> = 1086). Furthermore, this score explained 28% of the UWL-mortality relationship and 22% of the UWL-mobility limitation relationship beyond lifestyle and medical history, respectively. The score also predicted higher mortality and mobility limitation among those with intentional weight loss and weight gain, demonstrating a good Out-Of-Distribution generalizability. This metabolomic characterization of UWL is predictive of key aging outcomes in the Health ABC participants and captures a substantial portion of the mortality and mobility limitation risks related to unintentional weight loss, further validating the importance of these metabolite signatures.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 10","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aging Adipose-Derived Mesenchymal Stem Cells, Cultured on a Native Young Extracellular Matrix, Are Protected From Senescence and Apoptosis Along With Increased Expression of HLA-DR and CD74 Associated With PI3K Signaling 衰老脂肪来源的间充质干细胞,在原生年轻细胞外基质上培养,可以防止衰老和凋亡,同时增加与PI3K信号相关的HLA-DR和CD74的表达。
IF 7.1 1区 医学
Aging Cell Pub Date : 2025-08-05 DOI: 10.1111/acel.70165
Aaron O. Gonzalez, Parveez A. Abdul Azees, Jerry P. Chen, Milos Marinkovic, Brian Cao, Ting Liang, Peiqing Hu, Chih-Ko Yeh, David D. Dean, Yidong Bai, Xiao-Dong Chen
{"title":"Aging Adipose-Derived Mesenchymal Stem Cells, Cultured on a Native Young Extracellular Matrix, Are Protected From Senescence and Apoptosis Along With Increased Expression of HLA-DR and CD74 Associated With PI3K Signaling","authors":"Aaron O. Gonzalez,&nbsp;Parveez A. Abdul Azees,&nbsp;Jerry P. Chen,&nbsp;Milos Marinkovic,&nbsp;Brian Cao,&nbsp;Ting Liang,&nbsp;Peiqing Hu,&nbsp;Chih-Ko Yeh,&nbsp;David D. Dean,&nbsp;Yidong Bai,&nbsp;Xiao-Dong Chen","doi":"10.1111/acel.70165","DOIUrl":"10.1111/acel.70165","url":null,"abstract":"<p>Older adults are the primary population for cell-based therapies for age-related diseases, but the efficacy of administering autologous mesenchymal stem cells (MSCs) is impaired due to biological aging. In the present study, we cultured aging adipose (AD)-derived MSCs from &gt; 65-year-old donors on extracellular matrix (ECM) synthesized by human amniotic fluid-derived pluripotent stem cells (ECM Plus) versus tissue culture plastic (TCP) and hypothesized that ECM Plus provided an ideal “young” microenvironment for reactivating and preserving early-stage progenitor cells within aging AD-MSCs. To test our hypothesis, we serially sub-cultured aging AD-MSCs on ECM Plus or TCP and characterized the cells both phenotypically and functionally, and then analyzed the cells at the single-cell transcriptomic level for the mechanisms that control cell fate. The results showed that the maintenance of aging AD-MSCs on ECM Plus significantly restored their quantity and quality. The mechanisms responsible for these effects were associated with a remarkable up-regulation of intracellular CD74 when cells were maintained on ECM Plus compared to TCP, which triggered activation of the phosphoinositide-3-kinase (PI3K) pathway as a key modulator of cell survival (anti-apoptosis) and suppression of cellular senescence. Moreover, AD-MSCs maintained on ECM Plus increased their expression of HLA-DR and stimulated T cell activity. These findings challenge the “immune privilege” of allogeneic MSCs as a universal source for MSC-based therapies. The present study leads to a new paradigm for treating age-related diseases: serial administration of rejuvenated autologous MSCs, which may not only replace aged MSCs but also gradually reverse the aged microenvironment.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 9","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Local Growth Hormone Facilitates Aging of the Colon Epithelial Microenvironment 局部生长激素促进结肠上皮微环境的衰老。
IF 7.1 1区 医学
Aging Cell Pub Date : 2025-08-05 DOI: 10.1111/acel.70187
Vera Chesnokova, Svetlana Zonis, Richard Ainsworth, Tugce Apaydin, Christian Wong Valencia, Elora C. Greiner, Robert Barrett, Arminja N. Kettenbach, Shlomo Melmed
{"title":"Local Growth Hormone Facilitates Aging of the Colon Epithelial Microenvironment","authors":"Vera Chesnokova,&nbsp;Svetlana Zonis,&nbsp;Richard Ainsworth,&nbsp;Tugce Apaydin,&nbsp;Christian Wong Valencia,&nbsp;Elora C. Greiner,&nbsp;Robert Barrett,&nbsp;Arminja N. Kettenbach,&nbsp;Shlomo Melmed","doi":"10.1111/acel.70187","DOIUrl":"10.1111/acel.70187","url":null,"abstract":"<p>Aging is associated with the appearance of senescent cells secreting the senescence-associated secretome, facilitating a milieu favoring age-related microenvironmental changes. As we previously showed the production of local nonpituitary growth hormone (npGH) in senescent colon epithelial cells, we now elucidate mechanisms underlying npGH action in the nontumorous colon tissue microenvironment. We demonstrate autocrine npGH action in normal human colon cells (hNCC) infected with lentivirus-expressing hGH (lentiGH), as well as paracrine npGH action in hNCC cocultured with lentiGH hNCC and in intact human 3-dimensional intestinal organoids cocultured with organoids infected with lentiGH. Enriched gene ontology and pathway analysis of intact organoids exposed to paracrine npGH identified distorted extracellular matrix (ECM) and focal adhesion pathways concurrent with altered expression of ECM and cytoskeletal proteins. Significant phosphoprotein changes associated with the cytoskeleton and cell migration pathway occurred in GH-exposed hNCC. Paracrine npGH triggers these changes by activating epithelial-mesenchymal transition, as shown by suppression of E-cadherin and induction of Twist2 in cellular models, as well as in the colon of nude mice inoculated with GH-secreting xenografts. These changes are consistent with observed increased migration of hNCC overexpressing lentiGH, or in those cocultured with GH-secreting hNCC or with GH-secreting normal colon fibroblasts. Furthermore, whole exome sequencing detected increased structural variation in intact organoids cocultured with lentiGH-infected organoids, likely as a consequence of GH-mediated suppressed DNA damage repair, thereby favoring cell transformation. Our results indicate that local growth hormone facilitates aging of the colon epithelial microenvironment.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 10","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TSP50 in Neural Stem Cells Regulates Aging-Related Cognitive Decline and Neuroinflammation by Altering the Gut Microbiota 神经干细胞中的TSP50通过改变肠道菌群调节衰老相关的认知能力下降和神经炎症。
IF 7.1 1区 医学
Aging Cell Pub Date : 2025-08-05 DOI: 10.1111/acel.70188
Xiaoli Li, Yuecong Chen, Zhuoyi Gao, Xiaoling Liu, Zhenbo Song, Feng Gao, Shuyue Wang, Chunlei Yu, Luguo Sun, Yanxin Huang, Lihua Zheng, Guannan Wang, Ying Sun, Jiawei Li, Xiaoguang Yang, Yongli Bao
{"title":"TSP50 in Neural Stem Cells Regulates Aging-Related Cognitive Decline and Neuroinflammation by Altering the Gut Microbiota","authors":"Xiaoli Li,&nbsp;Yuecong Chen,&nbsp;Zhuoyi Gao,&nbsp;Xiaoling Liu,&nbsp;Zhenbo Song,&nbsp;Feng Gao,&nbsp;Shuyue Wang,&nbsp;Chunlei Yu,&nbsp;Luguo Sun,&nbsp;Yanxin Huang,&nbsp;Lihua Zheng,&nbsp;Guannan Wang,&nbsp;Ying Sun,&nbsp;Jiawei Li,&nbsp;Xiaoguang Yang,&nbsp;Yongli Bao","doi":"10.1111/acel.70188","DOIUrl":"10.1111/acel.70188","url":null,"abstract":"<p>Aging is a process of gradual decline in physical and cognitive function and is a major risk factor for mortality. Despite the increasing number of relevant studies, the mechanisms regulating the aging process have not been fully elucidated. Genetic factors have long been recognized as key factors in controlling the rate of aging. Testes-specific protease 50 (TSP50) has been shown to be involved in the regulation of embryonic development and intestinal homeostasis, but its role in the regulation of aging remains unclear. Here, we showed that TSP50 expression was reduced in the hippocampus of both aged humans and mice. TSP50 deficiency in neural stem cells (NSCs) drove accelerated aging in mice, characterized by exacerbated age-related cognitive impairments and significantly elevated neuroinflammation. Notably, aged mice with NSCs-specific knockout of TSP50 exhibited impaired intestinal mucosal barriers, dysbiosis of gut microbiota, and a marked reduction in the production of short-chain fatty acids (SCFAs). Restoring gut microbial ecology using fecal microbiota transplantation (FMT) and overexpressing TSP50 successfully alleviated aging-associated cognitive decline and neuroinflammation. Taken together, our study suggests that TSP50 plays a critical role in the aging process and identifies gut microbiota as a pivotal mediator of TSP50's influence on age-related cognitive decline and neuroinflammation. These findings highlight the potential therapeutic value of targeting TSP50 and gut microbiota for aging, offering insights into aging mechanisms and interventions for aging-related neurodegenerative diseases.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 10","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sex-Specific Aging Patterns of Gut Microbiota in Urban Chinese Adults: Guild-Based Analysis and Implications for Healthy Aging 中国城市成年人肠道微生物群的性别特异性衰老模式:基于行会的分析及其对健康老龄化的影响
IF 7.1 1区 医学
Aging Cell Pub Date : 2025-08-04 DOI: 10.1111/acel.70192
Jiongxing Fu, Wanghong Xu, Danxia Yu, Yu Jiang, Lei Wang, Hui Cai, Qinghua Xia, Xiao-Ou Shu, Wei Zheng
{"title":"Sex-Specific Aging Patterns of Gut Microbiota in Urban Chinese Adults: Guild-Based Analysis and Implications for Healthy Aging","authors":"Jiongxing Fu,&nbsp;Wanghong Xu,&nbsp;Danxia Yu,&nbsp;Yu Jiang,&nbsp;Lei Wang,&nbsp;Hui Cai,&nbsp;Qinghua Xia,&nbsp;Xiao-Ou Shu,&nbsp;Wei Zheng","doi":"10.1111/acel.70192","DOIUrl":"10.1111/acel.70192","url":null,"abstract":"<p>Gut microbial stability typically decreases with physiological aging. This decline may vary between sexes and can potentially be mitigated by adopting a healthy lifestyle. Microbial guilds, defined as functionally coherent groups of bacteria, may serve as meaningful ecological indicators of aging. This study included 2944 participants aged 51–89 years from the Shanghai Men's and Women's Health Studies. Using 16S rRNA gene sequencing and a guild-based approach, we evaluated the associations between gut microbiota and age in 1353 relatively healthy individuals. We found that women demonstrated a decline in the Chao1 index, an increase in Pielou evenness, and a remarkable shift in Bray–Curtis distance, whereas men exhibited an increase in Bray–Curtis uniqueness. Of the 45 age-related guilds identified, 16 (8 in men and 10 in women) were considered potential aging biomarkers (<i>p</i><sub>FDR</sub> &lt; 0.05), with Guild_6 (<i>Bifidobacterium</i> sp. dominated) and Guild_118 (<i>Veillonella dispar</i> dominated) being common to both sexes. These guilds were associated with consistent predicted functions, particularly 1,4-dihydroxy-2-naphthoate biosynthesis. We estimated sex-specific microbial age using random forest models and found that women and individuals with major chronic diseases had higher microbial ages. Prospective analysis revealed that an “old” microbial age was associated with a higher risk of type 2 diabetes (HR = 2.0, 95% CI: 1.1, 3.7). Individuals with healthier lifestyles had a 0.43-year lower microbial age (95% CI: −0.85, −0.01). Our findings elucidate the sex-differentiated aging patterns of gut microbiota in Chinese adults and imply the potential benefits of healthy lifestyle behaviors in slowing down microbiome aging.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 10","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70192","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Frailty-Based Plasma Proteomic Signature Capturing Overall Health and Well-Being in Older Adults 基于脆弱的血浆蛋白质组学特征捕捉老年人的整体健康和幸福。
IF 7.1 1区 医学
Aging Cell Pub Date : 2025-08-04 DOI: 10.1111/acel.70144
Sanish Sathyan, Fangyu Liu, Toshiko Tanaka, Luigi Ferrucci, Emmeline Ayers, B. Gwen Windham, Tina Gao, Erica F. Weiss, Julián Candia, Josef Coresh, Nir Barzilai, Sofiya Milman, Keenan A. Walker, Joe Verghese
{"title":"A Frailty-Based Plasma Proteomic Signature Capturing Overall Health and Well-Being in Older Adults","authors":"Sanish Sathyan,&nbsp;Fangyu Liu,&nbsp;Toshiko Tanaka,&nbsp;Luigi Ferrucci,&nbsp;Emmeline Ayers,&nbsp;B. Gwen Windham,&nbsp;Tina Gao,&nbsp;Erica F. Weiss,&nbsp;Julián Candia,&nbsp;Josef Coresh,&nbsp;Nir Barzilai,&nbsp;Sofiya Milman,&nbsp;Keenan A. Walker,&nbsp;Joe Verghese","doi":"10.1111/acel.70144","DOIUrl":"10.1111/acel.70144","url":null,"abstract":"<p>Frailty is an age-related syndrome characterized by an increased vulnerability to adverse health outcomes in the face of stressors. By deriving a blood-based proteomic signature for frailty, the current study aimed to enhance the understanding of frailty biology and created a person-specific predictor for the risk of frailty and other adverse age-related health outcomes. A 25-protein signature (proteomic frailty index [pFI]) predictive of the cumulative frailty index (FI) in the LonGenity cohort was derived using a penalized regression method. The pFI was significantly correlated with the FI at baseline (Pearson <i>r</i> = 0.58) and showed significant associations with age-related chronic conditions, incident mortality, and clinical measures. In an independent cohort of 5195 participants in the Atherosclerosis Risk in Communities study, pFI was successfully validated with measured FI (<i>r</i> = 0.61, <i>p</i> &lt; 0.001) and was associated with physical frailty at baseline (<i>p</i> &lt; 0.001). The pFI was significantly associated with physical, clinical, and cognitive measures, as well as incident mortality (HR [95% CI] = 1.13 [1.12–1.14]) and dementia (HR [95% CI] = 1.07 [1.05–1.09]) after accounting for demographic factors. The pFI was further validated against FI (<i>r</i> = 0.45, <i>p</i> &lt; 0.001) in a second independent study in 654 participants from the Baltimore Longitudinal Study of Aging. In conclusion, we identified and validated a 25-protein signature as an index of frailty that also captures overall well-being, health, and risk for key age-related diseases.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 9","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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