Nature aging最新文献

New genetic insights show how modifiable risk factors influence brain aging. 新的遗传学见解显示了可改变的风险因素如何影响大脑衰老。

IF 19.4

Nature aging Pub Date : 2025-10-09 DOI: 10.1038/s43587-025-00991-2

引用次数: 0

The secreted metabolite sensor CtBP2 links metabolism to healthy lifespan. 分泌代谢物传感器CtBP2将代谢与健康寿命联系起来。

IF 19.4

Nature aging Pub Date : 2025-10-08 DOI: 10.1038/s43587-025-00973-4

Motohiro Sekiya, Kenta Kainoh, Wanpei Chen, Daichi Yamazaki, Tomomi Tsuyuzaki, Yuto Kobari, Ayumi Nakata, Kenji Saito, Nao Aono-Soma, Ali Majid, Hiroshi Ohno, Takafumi Miyamoto, Takashi Matsuzaka, Rikako Nakajima, Takaaki Matsuda, Yuki Murayama, Yoko Sugano, Yoshinori Osaki, Hitoshi Iwasaki, Hitoshi Shimano

{"title":"The secreted metabolite sensor CtBP2 links metabolism to healthy lifespan.","authors":"Motohiro Sekiya, Kenta Kainoh, Wanpei Chen, Daichi Yamazaki, Tomomi Tsuyuzaki, Yuto Kobari, Ayumi Nakata, Kenji Saito, Nao Aono-Soma, Ali Majid, Hiroshi Ohno, Takafumi Miyamoto, Takashi Matsuzaka, Rikako Nakajima, Takaaki Matsuda, Yuki Murayama, Yoko Sugano, Yoshinori Osaki, Hitoshi Iwasaki, Hitoshi Shimano","doi":"10.1038/s43587-025-00973-4","DOIUrl":"https://doi.org/10.1038/s43587-025-00973-4","url":null,"abstract":"Within each cell, metabolite-sensing factors respond to coordinate metabolic homeostasis. How metabolic homeostasis is regulated intercellularly and how this may become dysregulated with age, however, remains underexplored. Here we describe a system regulated by a metabolite sensor, CtBP2. CtBP2 is secreted via exosomes in response to reductive metabolism, which is suppressed by oxidative stress. Exosomal CtBP2 administration extends lifespan in aged mice and improves healthspan in particular by reducing frailty. Mechanistically, we identify activation of CYB5R3 and AMPK downstream of exosomal CtBP2. Consistently, serum CtBP2 levels decrease with age and are negatively associated with cardiovascular disease incidence in humans yet are elevated in individuals from families with a history of longevity. Together our findings define a CtBP2-mediated metabolic system with potential for future clinical applications.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254386","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

CD4 T cells acquire Eomesodermin to modulate cellular senescence and aging. CD4 T细胞获得Eomesodermin来调节细胞衰老。

IF 19.4

Nature aging Pub Date : 2025-10-07 DOI: 10.1038/s43587-025-00953-8

Yehezqel Elyahu, Ilana Feygin, Ekaterina Eremenko, Noa Pinkas, Alon Zemer, Amit Shicht, Omer Berner, Roni Avigdory-Meiri, Anna Nemirovsky, Keren Reshef, Lior Roitman, Valery Krizhanovsky, Alon Monsonego

{"title":"CD4 T cells acquire Eomesodermin to modulate cellular senescence and aging.","authors":"Yehezqel Elyahu, Ilana Feygin, Ekaterina Eremenko, Noa Pinkas, Alon Zemer, Amit Shicht, Omer Berner, Roni Avigdory-Meiri, Anna Nemirovsky, Keren Reshef, Lior Roitman, Valery Krizhanovsky, Alon Monsonego","doi":"10.1038/s43587-025-00953-8","DOIUrl":"https://doi.org/10.1038/s43587-025-00953-8","url":null,"abstract":"Aging is characterized by the progressive deterioration of tissue structure and function, leading to increased vulnerability to diseases. Senescent cells (SCs) accumulate with age, but how the immune system regulates their burden is unclear. Here we show that CD4 T cells differentiate into Eomesodermin (Eomes)+CCL5+ T lymphocytes (CD4-Eomes) in a SC-rich environment and that a reduction in the SC load, achieved using senolytic drugs, was sufficient to halt this differentiation. We further demonstrate that eliminating CD4-Eomes cells at advanced age by selectively deleting the Eomes transcription factor in CD4 T cells results in increased accumulation of SCs, profound physical deterioration and a decreased lifespan. In liver cirrhosis, a model of localized chronic inflammation, CD4-Eomes cell elimination increased fibrosis, SC load and worsened the disease. Collectively, our findings demonstrate the fundamental role of CD4-Eomes cells in modulating tissue senescence, with implications for age-related diseases and longevity.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246046","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

Accelerating activity in the longevity biopharmaceutical sector. 加速长寿生物制药领域的活动。

IF 19.4

Nature aging Pub Date : 2025-10-06 DOI: 10.1038/s43587-025-00983-2

Michael S Ringel, Yue Zhang, Wen Kin Lim

引用次数: 0

Considerations for creating effective academic-industrial partnerships. 建立有效的学术-工业伙伴关系的考虑。

IF 19.4

Nature aging Pub Date : 2025-10-06 DOI: 10.1038/s43587-025-00988-x

Joe Swift, Angela Cucchi, Michael Chang, Richard G A Faragher, Carol A Holland, Itziar Tueros, Matthew J Dalby, Elizabeth G Canty-Laird

引用次数: 0

Phase separation meets energy generation to boost longevity. 相分离与能量产生相结合，延长寿命。

IF 19.4

Nature aging Pub Date : 2025-10-03 DOI: 10.1038/s43587-025-00989-w

Nektarios Tavernarakis

引用次数: 0

Genome-wide analysis of brain age identifies 59 associated loci and unveils relationships with mental and physical health. 对大脑年龄的全基因组分析确定了59个相关位点，并揭示了与精神和身体健康的关系。

IF 19.4

Nature aging Pub Date : 2025-10-03 DOI: 10.1038/s43587-025-00962-7

Philippe Jawinski, Helena Forstbach, Holger Kirsten, Frauke Beyer, Arno Villringer, A Veronica Witte, Markus Scholz, Stephan Ripke, Sebastian Markett

{"title":"Genome-wide analysis of brain age identifies 59 associated loci and unveils relationships with mental and physical health.","authors":"Philippe Jawinski, Helena Forstbach, Holger Kirsten, Frauke Beyer, Arno Villringer, A Veronica Witte, Markus Scholz, Stephan Ripke, Sebastian Markett","doi":"10.1038/s43587-025-00962-7","DOIUrl":"10.1038/s43587-025-00962-7","url":null,"abstract":"Neuroimaging and machine learning are advancing research into the mechanisms of biological aging. In this field, 'brain age gap' has emerged as a promising magnetic resonance imaging-based biomarker that quantifies the deviation between an individual's biological and chronological age of the brain. Here we conducted an in-depth genomic analysis of the brain age gap and its relationships with over 1,000 health traits. Genome-wide analyses in up to 56,348 individuals unveiled a heritability of 23-29% attributable to common genetic variants and highlighted 59 associated loci (39 novel). The leading locus encompasses MAPT, encoding the tau protein central to Alzheimer's disease. Genetic correlations revealed relationships with mental health, physical health, lifestyle and socioeconomic traits, including depressed mood, diabetes, alcohol intake and income. Mendelian randomization indicated a causal role of high blood pressure and type 2 diabetes in accelerated brain aging. Our study highlights key genes and pathways related to neurogenesis, immune-system-related processes and small GTPase binding, laying the foundation for further mechanistic exploration.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226555","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

Aging puts Leydig cells in a tough spot. 衰老使间质细胞处境艰难。

IF 19.4

Nature aging Pub Date : 2025-10-01 DOI: 10.1038/s43587-025-00995-y

Anna Kriebs

引用次数: 0

Author Correction: Senescent-like border-associated macrophages regulate cognitive aging via migrasome-mediated induction of paracrine senescence in microglia. 作者更正：衰老样边界相关巨噬细胞通过迁移体介导的小胶质细胞旁分泌衰老来调节认知衰老。

IF 19.4

Nature aging Pub Date : 2025-09-30 DOI: 10.1038/s43587-025-00994-z

Mengyan Hu, Xinmei Kang, Zhiruo Liu, Shisi Wang, Sanxin Liu, Chunyi Li, Danli Lu, Qin Qin, Yuxin Liu, Haotong Yi, Liling Yuan, Quentin Liu, Zhengqi Lu, Wei Cai

引用次数: 0

ZDHHC11-mediated palmitoylation alleviates chondrocyte senescence and serves as a therapeutic target for osteoarthritis. zdhhc11介导的棕榈酰化可缓解软骨细胞衰老，并可作为骨关节炎的治疗靶点。

IF 19.4

Nature aging Pub Date : 2025-09-30 DOI: 10.1038/s43587-025-00968-1

Kefan Wang, Wei He, Zhe Gong, Jun Gao, Tianyou Gao, Nan Pan, Dongze Wu, Yijie Yang, Zhuang Li, Xing Zhao, Mingliang Ji, Shuying Shen

{"title":"ZDHHC11-mediated palmitoylation alleviates chondrocyte senescence and serves as a therapeutic target for osteoarthritis.","authors":"Kefan Wang, Wei He, Zhe Gong, Jun Gao, Tianyou Gao, Nan Pan, Dongze Wu, Yijie Yang, Zhuang Li, Xing Zhao, Mingliang Ji, Shuying Shen","doi":"10.1038/s43587-025-00968-1","DOIUrl":"https://doi.org/10.1038/s43587-025-00968-1","url":null,"abstract":"Osteoarthritis (OA) is a whole-joint disorder that interferes with the quality of life in older individuals. Here we report that ZDHHC11 is highly expressed in articular chondrocytes but is downregulated in the degenerated cartilage of aged mice and patients with OA. ZDHHC11 prevents chondrocyte senescence and promotes cartilage anabolism, culminating in an improved OA phenotype. The deletion of Zdhhc11 in mice (Zdhhc11fl/fl) exacerbates OA progression in a destabilized medial meniscus model. Specifically, we identify ZDHHC11 as a key palmitoyltransferase whose depletion leads to a GNB2-dependent E3 ubiquitin ligase-mediated proteasomal degradation of APOD. Mechanistically, ZDHHC11-mediated palmitoylation alleviates OA progression by deactivating the GATA4-P65 signaling pathway. We also propose an original lipid nanoparticle-based platform for Zdhhc11 mRNA delivery to rejuvenate impaired cartilage by specifically targeting chondrocytes in vivo. Collectively, ZDHHC11-dependent palmitoylation is essential for ameliorating OA, and the targeted delivery of ZDHHC11 may serve as a promising strategy for future OA treatment.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202592","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