Nature aging最新文献_第2页

Comprehensive evaluation of plasma tau biomarkers for detecting and monitoring Alzheimer's disease in a multicenter and multiethnic aging population. 血浆tau生物标志物在多中心、多种族老龄化人群中检测和监测阿尔茨海默病的综合评价

IF 17

Nature aging Pub Date : 2025-06-23 DOI: 10.1038/s43587-025-00904-3

Guoyu Lan, Mengjie Wang, Fernando Gonzalez-Ortiz, Laihong Zhang, Anqi Li, Binyin Li, Mingxing Jiang, Jie Yang, Xuhui Chen, Dai Shi, Xiang Fan, Yue Cai, Pan Sun, Lin Liu, Jieyin Li, Zhengbo He, Lili Fang, Xin Zhou, Linting Chen, Yiying Wang, Mingxu Li, Zhen Liu, Qingyong Wang, Linsen Xu, Liemin Zhou, Guanxun Cheng, Xinlu Wang, Pengcheng Ran, Lu Wang, Kun Sun, Ying Han, Yihui Guan, Kaj Blennow, Fang Xie, Tengfei Guo

{"title":"Comprehensive evaluation of plasma tau biomarkers for detecting and monitoring Alzheimer's disease in a multicenter and multiethnic aging population.","authors":"Guoyu Lan, Mengjie Wang, Fernando Gonzalez-Ortiz, Laihong Zhang, Anqi Li, Binyin Li, Mingxing Jiang, Jie Yang, Xuhui Chen, Dai Shi, Xiang Fan, Yue Cai, Pan Sun, Lin Liu, Jieyin Li, Zhengbo He, Lili Fang, Xin Zhou, Linting Chen, Yiying Wang, Mingxu Li, Zhen Liu, Qingyong Wang, Linsen Xu, Liemin Zhou, Guanxun Cheng, Xinlu Wang, Pengcheng Ran, Lu Wang, Kun Sun, Ying Han, Yihui Guan, Kaj Blennow, Fang Xie, Tengfei Guo","doi":"10.1038/s43587-025-00904-3","DOIUrl":"10.1038/s43587-025-00904-3","url":null,"abstract":"Over 20% of patients with Alzheimer's disease (AD) worldwide are Chinese, although the efficacy of existing blood-based measures of AD biomarkers is largely unknown in Asian cohorts. Here we explored how plasma tau biomarkers correlated with cross-sectional and longitudinal AD-related outcomes and their diagnostic performance in 1,085 participants from three independent studies, including two Chinese cohorts, Greater-Bay-Area Healthy Aging Brain Study (n = 425) and Huashan (n = 297), and the North American Alzheimer's Disease Neuroimaging Initiative cohort (n = 363). Plasma p-tau217 performed best in classifying Aβ-positron emission tomography (PET) and tau-PET positivity throughout the AD continuum and correlated with all AD-related outcomes. A two-cutoff approach suggested that participants with intermediate plasma p-tau217 levels experienced rapid accumulation of Aβ-PET and entorhinal tau-PET, as well as accelerated hypometabolism and cognitive decline. Increased plasma p-tau217 was also associated with rapid longitudinal changes in Aβ-PET, tau-PET and neurodegeneration. These results suggest that plasma p-tau217 is superior in detecting multiple aspects of AD-related pathological changes and tracking disease progression.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-cell profiling identifies hair cell SLC35F1 deficiency as a signature of primate cochlear aging. 单细胞分析鉴定毛细胞SLC35F1缺陷是灵长类耳蜗老化的标志。

IF 17

Nature aging Pub Date : 2025-06-20 DOI: 10.1038/s43587-025-00896-0

Guoqiang Sun, Xiaolong Fu, Yandong Zheng, Guodong Hong, Ziyi Liu, Bilan Luo, Jinghui Lei, Dongliang Lv, Miao Chang, Yu Xiao, Siwei Guo, Shuai Ma, Ling Lu, Weiqi Zhang, Juan Carlos Izpisua Belmonte, Jing Qu, Si Wang, Renjie Chai, Guang-Hui Liu

{"title":"Single-cell profiling identifies hair cell SLC35F1 deficiency as a signature of primate cochlear aging.","authors":"Guoqiang Sun, Xiaolong Fu, Yandong Zheng, Guodong Hong, Ziyi Liu, Bilan Luo, Jinghui Lei, Dongliang Lv, Miao Chang, Yu Xiao, Siwei Guo, Shuai Ma, Ling Lu, Weiqi Zhang, Juan Carlos Izpisua Belmonte, Jing Qu, Si Wang, Renjie Chai, Guang-Hui Liu","doi":"10.1038/s43587-025-00896-0","DOIUrl":"10.1038/s43587-025-00896-0","url":null,"abstract":"Cochlear aging causes substantial hearing impairment in older adults, yet primate-specific mechanisms remain poorly characterized. Our comprehensive analysis combining single-cell and histopathological profiling in aging Macaca fascicularis demonstrates progressive cochlear degeneration featuring accelerated sensory hair cell loss, senescent spiral ganglion neurons with elevated neuroinflammation, and marked stria vascularis atrophy. We discovered that downregulation of transmembrane transport proteins, particularly SLC35F1, serves as a critical biomarker of hair cell aging. Functional validation through Slc35f1 knockdown in adult mice successfully recapitulated key aspects of age-related hearing loss, including hair cell degeneration and auditory function decline. Notably, we showed that long-term metformin administration at clinically relevant doses effectively delays cochlear aging in primates. These findings provide fundamental insights into the cellular and molecular basis of primate cochlear aging while establishing a foundation for developing targeted interventions against age-related hearing loss.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Skin health and biological aging. 皮肤健康与生物老化。

IF 17

Nature aging Pub Date : 2025-06-17 DOI: 10.1038/s43587-025-00901-6

David Furman, Johan Auwerx, Anne-Laure Bulteau, George Church, Virginie Couturaud, Laure Crabbe, Kelvin J A Davies, Anabelle Decottignies, Vadim N Gladyshev, Brian K Kennedy, Nicola Neretti, Carine Nizard, Karl Pays, Daisy Robinton, Vittorio Sebastiano, Rachel E B Watson, Meng C Wang, Knut Woltjen

{"title":"Skin health and biological aging.","authors":"David Furman, Johan Auwerx, Anne-Laure Bulteau, George Church, Virginie Couturaud, Laure Crabbe, Kelvin J A Davies, Anabelle Decottignies, Vadim N Gladyshev, Brian K Kennedy, Nicola Neretti, Carine Nizard, Karl Pays, Daisy Robinton, Vittorio Sebastiano, Rachel E B Watson, Meng C Wang, Knut Woltjen","doi":"10.1038/s43587-025-00901-6","DOIUrl":"https://doi.org/10.1038/s43587-025-00901-6","url":null,"abstract":"Accumulating evidence indicates that biological aging can be accelerated by environmental exposures, collectively called the 'exposome'. The skin, as the largest and most exposed organ, can be viewed as a 'window' for the deep exploration of the exposome and its effects on systemic aging. The complex interplay across hallmarks of aging in the skin and systemic biological aging suggests that physiological processes associated with skin aging influence, and are influenced by, systemic hallmarks of aging. This bidirectional relationship provides potential avenues for the prevention of accelerated biological aging and the identification of therapeutic targets. We provide a review of the interactions between skin exposure, aging hallmarks in the skin and associated systemic changes, and their implications in treatment and disease. We also discuss key questions that need to be addressed to maintain skin and overall health, highlighting the need for the development of precise biomarkers and advanced skin models.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 17

Nature aging Pub Date : 2025-06-10 DOI: 10.1038/s43587-025-00891-5

引用次数: 0

Boosting angiotensin-converting enzyme (ACE) in microglia protects against Alzheimer's disease in 5xFAD mice. 提高小胶质细胞中的血管紧张素转换酶（ACE）可预防5xFAD小鼠的阿尔茨海默病。

IF 17

Nature aging Pub Date : 2025-06-09 DOI: 10.1038/s43587-025-00879-1

Andrew R Gomez, Hyae Ran Byun, Shaogen Wu, A K M Ghulam Muhammad, Jasmine Ikbariyeh, Jaelin Chen, Alek Muro, Lin Li, Kenneth E Bernstein, Richard Ainsworth, Warren G Tourtellotte

{"title":"Boosting angiotensin-converting enzyme (ACE) in microglia protects against Alzheimer's disease in 5xFAD mice.","authors":"Andrew R Gomez, Hyae Ran Byun, Shaogen Wu, A K M Ghulam Muhammad, Jasmine Ikbariyeh, Jaelin Chen, Alek Muro, Lin Li, Kenneth E Bernstein, Richard Ainsworth, Warren G Tourtellotte","doi":"10.1038/s43587-025-00879-1","DOIUrl":"https://doi.org/10.1038/s43587-025-00879-1","url":null,"abstract":"Genome-wide association studies have identified many gene polymorphisms associated with an increased risk of developing late-onset Alzheimer's disease (LOAD). Many of these LOAD risk-associated alleles alter disease pathogenesis by influencing innate immune responses and lipid metabolism of microglia (MG). Here we show that boosting the expression of angiotensin-converting enzyme (ACE), a genome-wide association study LOAD risk-associated gene product, specifically in MG, reduces amyloid-β (Aβ) plaque load, preserves vulnerable neurons and excitatory synapses, and significantly reduces learning and memory abnormalities in the 5xFAD amyloid mouse model of AD. ACE-expressing MG surround plaques more frequently and they have increased Aβ phagocytosis, endolysosomal trafficking and spleen tyrosine kinase activation downstream of the major Aβ receptors, triggering receptor expressed on myeloid cells 2 (Trem2) and C-type lectin domain family 7 member A (Clec7a). These findings establish a role for ACE in enhancing microglial immune function and they identify a potential use for ACE-expressing MG as a cell-based therapy to augment endogenous microglial responses to Aβ in AD.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A blood-based epigenetic clock for intrinsic capacity predicts mortality and is associated with clinical, immunological and lifestyle factors. 以血液为基础的内在能力表观遗传时钟预测死亡率，并与临床、免疫和生活方式因素有关。

IF 17

Nature aging Pub Date : 2025-06-04 DOI: 10.1038/s43587-025-00883-5

Matías Fuentealba, Laure Rouch, Sophie Guyonnet, Jean-Marc Lemaitre, Philipe de Souto Barreto, Bruno Vellas, Sandrine Andrieu, David Furman

{"title":"A blood-based epigenetic clock for intrinsic capacity predicts mortality and is associated with clinical, immunological and lifestyle factors.","authors":"Matías Fuentealba, Laure Rouch, Sophie Guyonnet, Jean-Marc Lemaitre, Philipe de Souto Barreto, Bruno Vellas, Sandrine Andrieu, David Furman","doi":"10.1038/s43587-025-00883-5","DOIUrl":"https://doi.org/10.1038/s43587-025-00883-5","url":null,"abstract":"Age-related decline in intrinsic capacity (IC), defined as the sum of an individual's physical and mental capacities, is a cornerstone for promoting healthy aging by prioritizing maintenance of function over disease treatment. However, assessing IC is resource-intensive, and the molecular and cellular bases of its decline are poorly understood. Here we used the INSPIRE-T cohort (1,014 individuals aged 20-102 years) to construct the IC clock, a DNA methylation-based predictor of IC, trained on the clinical evaluation of cognition, locomotion, psychological well-being, sensory abilities and vitality. In the Framingham Heart Study, DNA methylation IC outperforms first-generation and second-generation epigenetic clocks in predicting all-cause mortality, and it is strongly associated with changes in molecular and cellular immune and inflammatory biomarkers, functional and clinical endpoints, health risk factors and lifestyle choices. These findings establish the IC clock as a validated tool bridging molecular readouts of aging and clinical assessments of IC.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Developing a blood-based epigenetic clock for intrinsic capacity. 为内在能力开发一种基于血液的表观遗传时钟。

IF 17

Nature aging Pub Date : 2025-06-04 DOI: 10.1038/s43587-025-00899-x

Xueqing Jia, Zuyun Liu

引用次数: 0

The secretome of senescent monocytes predicts age-related clinical outcomes in humans. 衰老单核细胞分泌组预测人类年龄相关的临床结果。

IF 17

Nature aging Pub Date : 2025-06-03 DOI: 10.1038/s43587-025-00877-3

Bradley Olinger, Reema Banarjee, Amit Dey, Dimitrios Tsitsipatis, Toshiko Tanaka, Anjana Ram, Thedoe Nyunt, Gulzar N Daya, Zhongsheng Peng, Mansi Shrivastava, Linna Cui, Julian Candia, Eleanor M Simonsick, Myriam Gorospe, Keenan A Walker, Luigi Ferrucci, Nathan Basisty

{"title":"The secretome of senescent monocytes predicts age-related clinical outcomes in humans.","authors":"Bradley Olinger, Reema Banarjee, Amit Dey, Dimitrios Tsitsipatis, Toshiko Tanaka, Anjana Ram, Thedoe Nyunt, Gulzar N Daya, Zhongsheng Peng, Mansi Shrivastava, Linna Cui, Julian Candia, Eleanor M Simonsick, Myriam Gorospe, Keenan A Walker, Luigi Ferrucci, Nathan Basisty","doi":"10.1038/s43587-025-00877-3","DOIUrl":"10.1038/s43587-025-00877-3","url":null,"abstract":"Cellular senescence increases with age and contributes to age-related declines and pathologies. We identified circulating biomarkers of senescence and related them to clinical traits in humans to facilitate future noninvasive assessment of individual senescence burden, and efficacy testing of novel senotherapeutics. Using a nanoparticle-based proteomic workflow, we profiled the senescence-associated secretory phenotype (SASP) in THP-1 monocytes and examined these proteins in 1,060 plasma samples from the Baltimore Longitudinal Study of Aging. Machine-learning models trained on THP-1 monocyte SASP associated SASP signatures with several age-related phenotypes in a test cohort, including body fat composition, blood lipids, inflammatory markers and mobility-related traits, among others. Notably, a subset of SASP-based predictions, including a high-impact SASP panel, were validated in InCHIANTI, an independent aging cohort. These results demonstrate the clinical relevance of the circulating SASP and identify potential senescence biomarkers that could inform future clinical studies.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gut microbiota-dependent increase in phenylacetic acid induces endothelial cell senescence during aging. 肠道微生物依赖的苯乙酸增加诱导内皮细胞衰老。

IF 17

Nature aging Pub Date : 2025-06-01 Epub Date: 2025-05-12 DOI: 10.1038/s43587-025-00864-8

Seyed Soheil Saeedi Saravi, Benoit Pugin, Florentin Constancias, Khatereh Shabanian, Marianne Spalinger, Aurélien Thomas, Sylvain Le Gludic, Taraneh Shabanian, Gergely Karsai, Manuel Colucci, Cristina Menni, Ilias Attaye, Xinyuan Zhang, Meret Sarah Allemann, Pratintip Lee, Alessia Visconti, Mario Falchi, Andrea Alimonti, Frank Ruschitzka, Francesco Paneni, Jürg H Beer

{"title":"Gut microbiota-dependent increase in phenylacetic acid induces endothelial cell senescence during aging.","authors":"Seyed Soheil Saeedi Saravi, Benoit Pugin, Florentin Constancias, Khatereh Shabanian, Marianne Spalinger, Aurélien Thomas, Sylvain Le Gludic, Taraneh Shabanian, Gergely Karsai, Manuel Colucci, Cristina Menni, Ilias Attaye, Xinyuan Zhang, Meret Sarah Allemann, Pratintip Lee, Alessia Visconti, Mario Falchi, Andrea Alimonti, Frank Ruschitzka, Francesco Paneni, Jürg H Beer","doi":"10.1038/s43587-025-00864-8","DOIUrl":"10.1038/s43587-025-00864-8","url":null,"abstract":"Endothelial cell senescence is a key driver of cardiovascular aging, yet little is known about the mechanisms by which it is induced in vivo. Here we show that the gut bacterial metabolite phenylacetic acid (PAA) and its byproduct, phenylacetylglutamine (PAGln), are elevated in aged humans and mice. Metagenomic analyses reveal an age-related increase in PAA-producing microbial pathways, positively linked to the bacterium Clostridium sp. ASF356 (Clos). We demonstrate that colonization of young mice with Clos increases blood PAA levels and induces endothelial senescence and angiogenic incompetence. Mechanistically, we find that PAA triggers senescence through mitochondrial H2O2 production, exacerbating the senescence-associated secretory phenotype. By contrast, we demonstrate that fecal acetate levels are reduced with age, compromising its function as a Sirt1-dependent senomorphic, regulating proinflammatory secretion and redox homeostasis. These findings define PAA as a mediator of gut-vascular crosstalk in aging and identify sodium acetate as a potential microbiome-based senotherapy to promote healthy aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"1025-1045"},"PeriodicalIF":17.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

hUSI is a robust transcriptome-based cellular senescence prediction tool. hUSI是一个强大的基于转录组的细胞衰老预测工具。

IF 17

Nature aging Pub Date : 2025-06-01 DOI: 10.1038/s43587-025-00894-2

引用次数: 0