Nature aging最新文献_第8页

Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence 衰老的骨髓巨噬细胞通过细胞外囊泡介导的旁分泌衰老诱导驱动全身衰老和与年龄相关的功能障碍

IF 17

Nature aging Pub Date : 2024-09-12 DOI: 10.1038/s43587-024-00694-0

Jing Hou, Kai-Xuan Chen, Chen He, Xiao-Xiao Li, Mei Huang, Yang-Zi Jiang, Yu-Rui Jiao, Qiao-Ni Xiao, Wen-Zhen He, Ling Liu, Nan-Yu Zou, Min Huang, Jie Wei, Ye Xiao, Mi Yang, Xiang-Hang Luo, Chao Zeng, Guang-Hua Lei, Chang-Jun Li

{"title":"Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence","authors":"Jing Hou, Kai-Xuan Chen, Chen He, Xiao-Xiao Li, Mei Huang, Yang-Zi Jiang, Yu-Rui Jiao, Qiao-Ni Xiao, Wen-Zhen He, Ling Liu, Nan-Yu Zou, Min Huang, Jie Wei, Ye Xiao, Mi Yang, Xiang-Hang Luo, Chao Zeng, Guang-Hua Lei, Chang-Jun Li","doi":"10.1038/s43587-024-00694-0","DOIUrl":"10.1038/s43587-024-00694-0","url":null,"abstract":"The accumulation and systemic propagation of senescent cells contributes to physiological aging and age-related pathology. However, which cell types are most susceptible to the aged milieu and could be responsible for the propagation of senescence has remained unclear. Here we found that physiologically aged bone marrow monocytes/macrophages (BMMs) propagate senescence to multiple tissues, through extracellular vesicles (EVs), and drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a target of microRNAs within aged BMM-EVs that regulates downstream effects on senescence and age-related dysfunction. Demonstrating therapeutic potential, we report that treatment with the PPARα agonist fenofibrate effectively restores tissue homeostasis in aged mice. Suggesting conservation to humans, in a cohort study of 7,986 participants, we found that fenofibrate use is associated with a reduced risk of age-related chronic disease and higher life expectancy. Together, our findings establish that BMMs can propagate senescence to distant tissues and cause age-related dysfunction, and they provide supportive evidence for fenofibrate to extend healthy lifespan. Hou, Chen et al. show that aged bone marrow macrophages propagate senescence to multiple tissues in vivo, through extracellular vesicles containing PPARα-targeted microRNAs. They demonstrate the therapeutic potential of intervening in this process using the PPARα agonist fenofibrate.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 11","pages":"1562-1581"},"PeriodicalIF":17.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00694-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142225106","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

Incompetent neck valves threaten the aging brain 不健全的颈部瓣膜威胁老化的大脑

IF 17

Nature aging Pub Date : 2024-09-11 DOI: 10.1038/s43587-024-00707-y

Monica M. Santisteban, Costantino Iadecola

引用次数: 0

Publisher Correction: A plasma protein-based risk score to predict hip fractures 出版商更正：预测髋部骨折的血浆蛋白风险评分。

IF 17

Nature aging Pub Date : 2024-09-10 DOI: 10.1038/s43587-024-00717-w

Thomas R. Austin, Maria Nethander, Howard A. Fink, Anna E. Törnqvist, Diana I. Jalal, Petra Buzkova, Joshua I. Barzilay, Laura Carbone, Maiken E. Gabrielsen, Louise Grahnemo, Tianyuan Lu, Kristian Hveem, Christian Jonasson, Jorge R. Kizer, Arnulf Langhammer, Kenneth J. Mukamal, Robert E. Gerszten, Bruce M. Psaty, John A. Robbins, Yan V. Sun, Anne Heidi Skogholt, John A. Kanis, Helena Johansson, Bjørn Olav Åsvold, Rodrigo J. Valderrabano, Jie Zheng, J. Brent Richards, Eivind Coward, Claes Ohlsson

引用次数: 0

Preexisting senescent fibroblasts in the aged bladder create a tumor-permissive niche through CXCL12 secretion 老化膀胱中已有的衰老成纤维细胞通过分泌 CXCL12 创造出有利于肿瘤生长的生态位

IF 17

Nature aging Pub Date : 2024-09-09 DOI: 10.1038/s43587-024-00704-1

Satoru Meguro, Yoshikazu Johmura, Teh-Wei Wang, Satoshi Kawakami, Shota Tanimoto, Satotaka Omori, Yuki T. Okamura, Seiji Hoshi, Emina Kayama, Kiyoshi Yamaguchi, Seira Hatakeyama, Satoshi Yamazaki, Eigo Shimizu, Seiya Imoto, Yoichi Furukawa, Yoshiyuki Kojima, Makoto Nakanishi

{"title":"Preexisting senescent fibroblasts in the aged bladder create a tumor-permissive niche through CXCL12 secretion","authors":"Satoru Meguro, Yoshikazu Johmura, Teh-Wei Wang, Satoshi Kawakami, Shota Tanimoto, Satotaka Omori, Yuki T. Okamura, Seiji Hoshi, Emina Kayama, Kiyoshi Yamaguchi, Seira Hatakeyama, Satoshi Yamazaki, Eigo Shimizu, Seiya Imoto, Yoichi Furukawa, Yoshiyuki Kojima, Makoto Nakanishi","doi":"10.1038/s43587-024-00704-1","DOIUrl":"10.1038/s43587-024-00704-1","url":null,"abstract":"Aging is a major risk factor for cancer, but the precise mechanism by which aging promotes carcinogenesis remains largely unknown. Here, using genetically modified mouse models, we show that p16high senescent (p16h-sn) fibroblasts accumulate with age, constitute inflammatory cancer-associated fibroblasts (CAFs) and promote tumor growth in bladder cancer models. Single-cell RNA sequencing of fibroblasts from aged mice revealed higher expression of the C–X–C motif chemokine 12 gene (Cxcl12) in p16h-sn fibroblasts than in p16low fibroblasts. Elimination of p16h-sn cells or inhibition of CXCL12 signaling notebly suppressed bladder tumor growth in vivo. We identified high expression levels of SMOC2, GUCY1A1 (GUCY1A3), CXCL12, CRISPLD2, GAS1 and LUM as a signature of p16h-sn CAFs in humans and mice, which was associated with age and poor prognosis in patients with advanced and nonadvanced bladder cancer. Here we show that p16h-sn fibroblasts in the aged bladder create a cancer-permissive niche and promote tumor growth by secreting CXCL12. Meguro et al. show an accumulation of p16high senescent fibroblasts in the aging bladder that serves as a cancer-permissive niche and promotes tumor growth by secreting CXCL12. Inhibition of senescence or CXCL12 signaling suppresses bladder tumor growth.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 11","pages":"1582-1597"},"PeriodicalIF":17.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00704-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196082","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

Rejuvenation of aged oocyte through exposure to young follicular microenvironment 暴露于年轻卵泡微环境中的高龄卵母细胞返老还童

IF 17

Nature aging Pub Date : 2024-09-09 DOI: 10.1038/s43587-024-00697-x

HaiYang Wang, Zhongwei Huang, Xingyu Shen, Yaelim Lee, XinJie Song, Chang Shu, Lik Hang Wu, Leroy Sivappiragasam Pakkiri, Poh Leong Lim, Xi Zhang, Chester Lee Drum, Jin Zhu, Rong Li

{"title":"Rejuvenation of aged oocyte through exposure to young follicular microenvironment","authors":"HaiYang Wang, Zhongwei Huang, Xingyu Shen, Yaelim Lee, XinJie Song, Chang Shu, Lik Hang Wu, Leroy Sivappiragasam Pakkiri, Poh Leong Lim, Xi Zhang, Chester Lee Drum, Jin Zhu, Rong Li","doi":"10.1038/s43587-024-00697-x","DOIUrl":"10.1038/s43587-024-00697-x","url":null,"abstract":"Reproductive aging is a major cause of fertility decline, attributed to decreased oocyte quantity and developmental potential. A possible cause is aging of the surrounding follicular somatic cells that support oocyte growth and development by providing nutrients and regulatory factors. Here, by creating chimeric follicles, whereby an oocyte from one follicle was transplanted into and cultured within another follicle whose native oocyte was removed, we show that young oocytes cultured in aged follicles exhibited impeded meiotic maturation and developmental potential, whereas aged oocytes cultured within young follicles were significantly improved in rates of maturation, blastocyst formation and live birth after in vitro fertilization and embryo implantation. This rejuvenation of aged oocytes was associated with enhanced interaction with somatic cells, transcriptomic and metabolomic remodeling, improved mitochondrial function and higher fidelity of meiotic chromosome segregation. These findings provide the basis for a future follicular somatic cell-based therapy to treat female infertility. Oocyte quality declines during aging. Here the authors show that oocytes from aged mice cultured within follicles from young mice have improved developmental potential. Aged oocytes cultured within young follicles have enhanced interaction with somatic cells, improved mitochondrial function and better meiotic chromosome segregation.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1194-1210"},"PeriodicalIF":17.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196159","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

Stromal cell dysfunction contributes to thymic decline in aging 基质细胞功能障碍导致胸腺衰老。

IF 17

Nature aging Pub Date : 2024-09-06 DOI: 10.1038/s43587-024-00711-2

Hannah Walters

引用次数: 0

Spermidine controls autophagy during fasting 精氨酸在禁食期间控制自噬。

IF 17

Nature aging Pub Date : 2024-09-04 DOI: 10.1038/s43587-024-00710-3

Anna Kriebs

引用次数: 0

Older age reduces mtDNA mutation inheritance 年龄越大，mtDNA 变异的遗传性越低。

IF 17

Nature aging Pub Date : 2024-09-04 DOI: 10.1038/s43587-024-00701-4

Polyxeni Papadea, Nils-Göran Larsson

引用次数: 0

DNA hydroxymethylation in aging 衰老过程中的 DNA 羟甲基化。

IF 17

Nature aging Pub Date : 2024-09-04 DOI: 10.1038/s43587-024-00709-w

George Andrew S. Inglis

引用次数: 0

Loss of coordination between basic cellular processes in human aging 人类衰老过程中基本细胞过程之间失去协调。

IF 17

Nature aging Pub Date : 2024-09-03 DOI: 10.1038/s43587-024-00696-y

Ana Carolina Leote, Francisco Lopes, Andreas Beyer

{"title":"Loss of coordination between basic cellular processes in human aging","authors":"Ana Carolina Leote, Francisco Lopes, Andreas Beyer","doi":"10.1038/s43587-024-00696-y","DOIUrl":"10.1038/s43587-024-00696-y","url":null,"abstract":"Age-related loss of gene expression coordination has been reported for distinct cell types and may lead to impaired cellular function. Here we propose a method for quantifying age-related changes in transcriptional regulatory relationships between genes, based on a model learned from external data. We used this method to uncover age-related trends in gene–gene relationships across eight human tissues, which demonstrates that reduced co-expression may also result from coordinated transcriptional responses. Our analyses reveal similar numbers of strengthening and weakening gene–gene relationships with age, impacting both tissue-specific (for example, coagulation in blood) and ubiquitous biological functions. Regulatory relationships becoming weaker with age were established mostly between genes operating in distinct cellular processes. As opposed to that, regulatory relationships becoming stronger with age were established both within and between different cellular functions. Our work reveals that, although most transcriptional regulatory gene–gene relationships are maintained during aging, those with declining regulatory coupling result mostly from a loss of coordination between distinct cellular processes. Age-related loss of gene expression coordination may contribute to impaired cellular function. In this study, the authors analyzed age-related trends in gene–gene relationships. They found that expression control often remains intact among genes involved in shared cellular functions while the coordination between functions tends to decline.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1432-1445"},"PeriodicalIF":17.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00696-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127775","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