Nature aging最新文献_第2页

Publisher Correction: Transposable element methylation tracks age. 出版商更正：转座因子甲基化与年龄有关。

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Nature aging Pub Date : 2025-07-01 DOI: 10.1038/s43587-025-00922-1

Bernadette Hotzi, Tibor Vellai

引用次数: 0

The GNPC provides a proteomic resource for biomarker discovery and mechanistic insight in neurodegenerative disease. GNPC为神经退行性疾病的生物标志物发现和机制洞察提供了蛋白质组学资源。

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Nature aging Pub Date : 2025-07-01 DOI: 10.1038/s43587-025-00920-3

Simon Lovestone, Farhad Imam

引用次数: 0

Emerging role of mitochondrial calcium levels in cellular senescence and in switching cell fates. 线粒体钙水平在细胞衰老和细胞命运转换中的新作用。

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Nature aging Pub Date : 2025-07-01 DOI: 10.1038/s43587-025-00887-1

Céline Margand, Pablo Morgado-Cáceres, Ulises Ahumada-Castro, J César Cárdenas, Nadine Martin, David Bernard

引用次数: 0

Association of midlife hearing impairment and hearing aid use with incident dementia: analysis of two UK-based longitudinal cohort studies. 中年听力障碍和助听器使用与痴呆事件的关联：两项英国纵向队列研究的分析。

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Nature aging Pub Date : 2025-07-01 DOI: 10.1038/s43587-025-00914-1

Marcos D Machado-Fragua, Aurore Fayosse, Julien Dumurgier, Mika Kivimaki, Céline Ben Hassen, Gill Livingston, Claire Paquet, Séverine Sabia, Archana Singh-Manoux

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。

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Nature aging Pub Date : 2025-07-01 Epub 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":"1266-1279"},"PeriodicalIF":17.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217976","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

Author Correction: Single-cell and spatial RNA sequencing identify divergent microenvironments and progression signatures in early- versus late-onset prostate cancer. 作者更正：单细胞和空间RNA测序鉴定了早发性前列腺癌与晚发性前列腺癌不同的微环境和进展特征。

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Nature aging Pub Date : 2025-07-01 DOI: 10.1038/s43587-025-00892-4

Yifei Cheng, Bingxin Liu, Junyi Xin, Xiaobin Wu, Wenchao Li, Jinwei Shang, Jiajin Wu, Zhengdong Zhang, Bin Xu, Mulong Du, Gong Cheng, Meilin Wang

引用次数: 0

Age-dependent accumulation of mitochondrial tRNA mutations in mouse kidneys linked to mitochondrial kidney diseases. 与线粒体肾病相关的小鼠肾脏线粒体tRNA突变的年龄依赖性积累

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Nature aging Pub Date : 2025-07-01 Epub Date: 2025-06-27 DOI: 10.1038/s43587-025-00909-y

Leping Zhang, Zhe Xu, Jia Jing, Guoshi Chai, Guanglei Xie, Yanfei Ru, Qunyu Lv, Xiang Zuo, Qian Zhang, Jiatong Chen, He Jin, Ning Liu, Minghua Kong, Bin Shen, Mingxi Liu, Lei Jiang, Xi Wang, Yanxiao Zhang, Min Jiang

{"title":"Age-dependent accumulation of mitochondrial tRNA mutations in mouse kidneys linked to mitochondrial kidney diseases.","authors":"Leping Zhang, Zhe Xu, Jia Jing, Guoshi Chai, Guanglei Xie, Yanfei Ru, Qunyu Lv, Xiang Zuo, Qian Zhang, Jiatong Chen, He Jin, Ning Liu, Minghua Kong, Bin Shen, Mingxi Liu, Lei Jiang, Xi Wang, Yanxiao Zhang, Min Jiang","doi":"10.1038/s43587-025-00909-y","DOIUrl":"10.1038/s43587-025-00909-y","url":null,"abstract":"Heteroplasmic pathogenic mitochondrial DNA (mtDNA) mutations are key drivers of mitochondrial diseases, yet their tissue-specific and cell-specific accumulation patterns during aging and the mechanistic links to pathology remain poorly understood. In this study, we employed DddA-derived cytosine base editor technology to generate three mouse models harboring distinct pathogenic mitochondrial tRNA mutations. These mutations exhibited age-dependent accumulation in the kidneys, leading to severe kidney defects that well recapitulate human mitochondrial kidney disease. Mitochondrial single-cell assay for transposase-accessible chromatin with sequencing (mtscATAC-seq) revealed unique heteroplasmy dynamics across different kidney cell types: podocytes exhibited a positive selection for mutant mtDNA, whereas tubular epithelial cells displayed neutral drift of mutations during aging. Integrative analyses combining mtscATAC-seq, single-cell RNA sequencing and spatially enhanced resolution omics sequencing further identified molecular changes in high-mutant defective cells, including increased AP-1 family transcription factor activity, tubular epithelial cell proliferation and immune activation, which contribute to disease progression. Our study underscores the importance of kidney function monitoring in patients with mitochondrial disease, particularly in older adults, and establishes robust preclinical models to facilitate the development of therapeutic strategies.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"1317-1339"},"PeriodicalIF":17.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513026","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

Body-to-brain insulin and Notch signaling regulates memory through neuronal CREB activity. 体对脑胰岛素和Notch信号通过神经元CREB活动调节记忆。

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Nature aging Pub Date : 2025-07-01 Epub Date: 2025-05-27 DOI: 10.1038/s43587-025-00873-7

Shiyi Zhou, Katherine E Novak, Rachel Kaletsky, Yifei Weng, Jonathan St Ange, Morgan E Stevenson, Erik Toraason, Yanping Zhang, Wenhong Zhang, Meng-Qiu Dong, Coleen T Murphy

{"title":"Body-to-brain insulin and Notch signaling regulates memory through neuronal CREB activity.","authors":"Shiyi Zhou, Katherine E Novak, Rachel Kaletsky, Yifei Weng, Jonathan St Ange, Morgan E Stevenson, Erik Toraason, Yanping Zhang, Wenhong Zhang, Meng-Qiu Dong, Coleen T Murphy","doi":"10.1038/s43587-025-00873-7","DOIUrl":"10.1038/s43587-025-00873-7","url":null,"abstract":"While memory regulation is predominantly understood as autonomous to neurons, factors outside the brain can also affect neuronal function. In Caenorhabditis elegans, the insulin/IGF-1-like signaling (IIS) pathway regulates longevity, metabolism and memory: long-lived daf-2 insulin/IGF-1 receptor mutants more than double memory duration after a single training session, and it was assumed that memory regulation was strictly neuronal. However, here we show that degradation of DAF-2 in the hypodermis also greatly extends memory, via expression of the diffusible Notch ligand, OSM-11, which in turn activates Notch signaling in neurons. Single-nucleus RNA sequencing of neurons revealed increased expression of CREB and other memory genes. Furthermore, in aged animals, activation of the hypodermal IIS-Notch pathway as well as OSM-11 overexpression rescue both memory and learning via CREB activity. Thus, insulin signaling in the liver-like hypodermis non-autonomously regulates neuronal function, providing a systemic connection between metabolism and memory through IIS-Notch-CREB signaling from the body to the brain.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"1232-1248"},"PeriodicalIF":17.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164454","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

The geroprotectors trametinib and rapamycin combine additively to extend mouse healthspan and lifespan. 老年保护剂曲美替尼和雷帕霉素加用可延长小鼠健康寿命和寿命。

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Nature aging Pub Date : 2025-07-01 Epub Date: 2025-05-28 DOI: 10.1038/s43587-025-00876-4

Lisonia Gkioni, Tobias Nespital, Maarouf Baghdadi, Carolina Monzó, Jitin Bali, Taim Nassr, Anna Lena Cremer, Andreas Beyer, Joris Deelen, Heiko Backes, Sebastian Grönke, Linda Partridge

{"title":"The geroprotectors trametinib and rapamycin combine additively to extend mouse healthspan and lifespan.","authors":"Lisonia Gkioni, Tobias Nespital, Maarouf Baghdadi, Carolina Monzó, Jitin Bali, Taim Nassr, Anna Lena Cremer, Andreas Beyer, Joris Deelen, Heiko Backes, Sebastian Grönke, Linda Partridge","doi":"10.1038/s43587-025-00876-4","DOIUrl":"10.1038/s43587-025-00876-4","url":null,"abstract":"Suppression of the insulin-IGF-mTORC1-Ras network ameliorates aging in animals. Many drugs have targets in the network because of its roles in cancer and metabolic disease and are candidates for repurposing as geroprotectors. Rapamycin, an established geroprotective drug, blocks mTORC1 signaling, and trametinib inhibits the Ras-MEK-ERK pathway. In this study, we assessed survival and health of male and female mice treated with trametinib, rapamycin or their combination. We show here that trametinib treatment extended lifespan in both sexes and that its combination with rapamycin was additive. Combination treatment reduced liver tumors in both sexes and spleen tumors in male mice, blocked the age-related increase in brain glucose uptake and strongly reduced inflammation in brain, kidney, spleen and muscle and circulating levels of pro-inflammatory cytokines. We conclude that trametinib is a geroprotector in mice and that its combination with rapamycin is more effective than either drug alone, making the combination a candidate for repurposing as a gerotherapy in humans.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"1249-1265"},"PeriodicalIF":17.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176372","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

Senescent macrophages induce ferroptosis in skeletal muscle and accelerate osteoarthritis-related muscle atrophy. 衰老巨噬细胞诱导骨骼肌铁下垂，加速骨关节炎相关肌肉萎缩。

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Nature aging Pub Date : 2025-07-01 Epub Date: 2025-06-27 DOI: 10.1038/s43587-025-00907-0

Wei Xiang, Tongyi Zhang, Bingfei Li, Song Li, Bin Zhang, Shunzheng Fang, Lifeng Chen, Yunquan Gong, Bo Huang, Daibo Feng, Jinhui Wu, Jing Yuan, Yaran Wu, Xiaojing Yan, Runze Jin, Xiaoqi Zhang, Xiangqin Fang, Jiqin Lian, Lin Chen, Siru Zhou, Zhenhong Ni

{"title":"Senescent macrophages induce ferroptosis in skeletal muscle and accelerate osteoarthritis-related muscle atrophy.","authors":"Wei Xiang, Tongyi Zhang, Bingfei Li, Song Li, Bin Zhang, Shunzheng Fang, Lifeng Chen, Yunquan Gong, Bo Huang, Daibo Feng, Jinhui Wu, Jing Yuan, Yaran Wu, Xiaojing Yan, Runze Jin, Xiaoqi Zhang, Xiangqin Fang, Jiqin Lian, Lin Chen, Siru Zhou, Zhenhong Ni","doi":"10.1038/s43587-025-00907-0","DOIUrl":"10.1038/s43587-025-00907-0","url":null,"abstract":"Muscle atrophy around joints is a common issue for people with osteoarthritis (OA), but its causes are poorly understood. Here we demonstrate that chronic inflammation in quadriceps muscle coincides with OA in mice, characterized by an increase in macrophages, activation of inflammatory pathways and tissue vascularization. We show that, during OA progression, macrophages progressively exhibit increasing phenotypes of senescence and promote muscle atrophy through paracrine induction of ferroptosis. Mechanistically, iron overload-induced mitochondrial damage results in reduced asparagine metabolites, impairing coenzyme Q10 (CoQ10) synthesis by inhibiting mTORC1-HMGCR signaling. Ultimately, this cascade enhances lipid peroxidation and promotes ferroptosis in skeletal muscle cells. We show that the cardiac medication CoQ10 can attenuate muscle atrophy by inhibiting ferroptosis, thereby reducing pathological damage to OA joints. Our findings offer insights for the potential management of muscle atrophy in patients with OA.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"1295-1316"},"PeriodicalIF":17.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513027","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