Nature aging最新文献_第8页

Blocking IL-11 improves healthspan and lifespan in mice 阻断 IL-11 可改善小鼠的健康和寿命。

IF 17

Nature aging Pub Date : 2024-08-08 DOI: 10.1038/s43587-024-00699-9

Hannah Walters

引用次数: 0

Multiorgan biological age shows that no organ system is an island 多器官生物年龄表明，任何器官系统都不是一座孤岛。

IF 17

Nature aging Pub Date : 2024-08-02 DOI: 10.1038/s43587-024-00690-4

引用次数: 0

Maternal age enhances purifying selection on pathogenic mutations in complex I genes of mammalian mtDNA 母体年龄增强了对哺乳动物mtDNA I复合基因致病突变的纯化选择。

IF 17

Nature aging Pub Date : 2024-07-29 DOI: 10.1038/s43587-024-00672-6

Yanfei Ru, Xiaoling Deng, Jiatong Chen, Leping Zhang, Zhe Xu, Qunyu Lv, Shiyun Long, Zijian Huang, Minghua Kong, Jing Guo, Min Jiang

{"title":"Maternal age enhances purifying selection on pathogenic mutations in complex I genes of mammalian mtDNA","authors":"Yanfei Ru, Xiaoling Deng, Jiatong Chen, Leping Zhang, Zhe Xu, Qunyu Lv, Shiyun Long, Zijian Huang, Minghua Kong, Jing Guo, Min Jiang","doi":"10.1038/s43587-024-00672-6","DOIUrl":"10.1038/s43587-024-00672-6","url":null,"abstract":"Mitochondrial diseases, caused mainly by pathogenic mitochondrial DNA (mtDNA) mutations, pose major challenges due to the lack of effective treatments. Investigating the patterns of maternal transmission of mitochondrial diseases could pave the way for preventive approaches. In this study, we used DddA-derived cytosine base editors (DdCBEs) to generate two mouse models, each haboring a single pathogenic mutation in complex I genes (ND1 and ND5), replicating those found in human patients. Our findings revealed that both mutations are under strong purifying selection during maternal transmission and occur predominantly during postnatal oocyte maturation, with increased protein synthesis playing a vital role. Interestingly, we discovered that maternal age intensifies the purifying selection, suggesting that older maternal age may offer a protective effect against the transmission of deleterious mtDNA mutations, contradicting the conventional notion that maternal age correlates with increased transmitted mtDNA mutations. As collecting comprehensive clinical data is needed to understand the relationship between maternal age and transmission patterns in humans, our findings may have profound implications for reproductive counseling of mitochondrial diseases, especially those involving complex I gene mutations. Mitochondrial DNA mutations are subject to purifying selection in the female germline, limiting the transmission of pathogenic variants. In this study, the authors used two mouse models that harbor pathogenic mutations in mitochondrial complex I and observed that maternal age intensifies purifying selection processes.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1211-1230"},"PeriodicalIF":17.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794453","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

mTOR links nutrients, inflammaging and lifespan mTOR 将营养、炎症和寿命联系在一起。

IF 17

Nature aging Pub Date : 2024-07-26 DOI: 10.1038/s43587-024-00681-5

Helena M. Cochemé, Jesús Gil

引用次数: 0

Separation of reproductive decline from lifespan extension during methionine restriction 蛋氨酸限制过程中生殖能力下降与寿命延长的分离

IF 17

Nature aging Pub Date : 2024-07-26 DOI: 10.1038/s43587-024-00674-4

Fangchao Wei, Shiyu Liu, Juan Liu, Yudong Sun, Annamarie E. Allen, Michael A. Reid, Jason W. Locasale

{"title":"Separation of reproductive decline from lifespan extension during methionine restriction","authors":"Fangchao Wei, Shiyu Liu, Juan Liu, Yudong Sun, Annamarie E. Allen, Michael A. Reid, Jason W. Locasale","doi":"10.1038/s43587-024-00674-4","DOIUrl":"10.1038/s43587-024-00674-4","url":null,"abstract":"Lifespan-extending interventions are generally thought to result in reduced fecundity. The generality of this principle and how it may extend to nutrition and metabolism is not understood. We considered dietary methionine restriction (MR), a lifespan-extending intervention linked to Mediterranean and plant-based diets. Using a chemically defined diet that we developed for Drosophila melanogaster, we surveyed the nutritional landscape in the background of MR and found that folic acid, a vitamin linked to one-carbon metabolism, notably was the lone nutrient that restored reproductive capacity while maintaining lifespan extension. In vivo isotope tracing, metabolomics and flux analysis identified the tricarboxylic cycle and redox coupling as major determinants of the MR-folic acid benefits, in part, as they related to sperm function. Together these findings suggest that dietary interventions optimized for longevity may be separable from adverse effects such as reproductive decline. Methionine restriction decreases fecundity and increases lifespan in flies. Here Wei et al. show that supplementing folic acid, associated with one-carbon metabolism, during methionine restriction in flies, mitigates the decline in fertility while retaining the intervention’s life-extending benefits.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 8","pages":"1089-1101"},"PeriodicalIF":17.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141768398","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 microbial features and circulating metabolomic signatures of frailty in older adults 老年人肠道微生物特征和循环代谢组特征与虚弱有关。

IF 17

Nature aging Pub Date : 2024-07-25 DOI: 10.1038/s43587-024-00678-0

Yanni Pu, Zhonghan Sun, Hui Zhang, Qingxia Huang, Zhengdong Wang, Zhendong Mei, Peilu Wang, Mengmeng Kong, Wenjun Yang, Chenhao Lin, Xiaofeng Zhou, Shuchun Lin, Qiumin Huang, Lili Huang, Liang Sun, Changzheng Yuan, Qian Xu, Huiru Tang, Xiaofeng Wang, Yan Zheng

{"title":"Gut microbial features and circulating metabolomic signatures of frailty in older adults","authors":"Yanni Pu, Zhonghan Sun, Hui Zhang, Qingxia Huang, Zhengdong Wang, Zhendong Mei, Peilu Wang, Mengmeng Kong, Wenjun Yang, Chenhao Lin, Xiaofeng Zhou, Shuchun Lin, Qiumin Huang, Lili Huang, Liang Sun, Changzheng Yuan, Qian Xu, Huiru Tang, Xiaofeng Wang, Yan Zheng","doi":"10.1038/s43587-024-00678-0","DOIUrl":"10.1038/s43587-024-00678-0","url":null,"abstract":"Frailty, a multidimensional indicator of suboptimal aging, reflects cumulative declines across multiple physiological systems. Although age-related changes have been reported in gut microbiota, their role in healthy aging remains unclear. In this study, we calculated frailty index (FI) from 33 health-related items to reflect the overall health status of 1,821 older adults (62–96 years, 55% female) and conducted multi-omics analysis using gut metagenomic sequencing data and plasma metabolomic data. We identified 18 microbial species and 17 metabolites shifted along with frailty severity, with stronger links observed in females. The associations of nine species, including various Clostridium species and Faecalibacterium prausnitzii, with FI were reproducible in two external populations. Plasma glycerol levels, white blood cell count and kidney function partially mediated these associations. A composite microbial score derived from FI significantly predicted 2-year mortality (adjusted hazard ratio across extreme quartiles, 2.86; 95% confidence interval, 1.38–5.93), highlighting the potential of microbiota-based strategies for risk stratification in older adults. This study reveals gut microbial and metabolomic features associated with the severity of frailty, demonstrating that these microbial features outperform traditional assessment tools in identifying individuals at high risk of frailty and mortality.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1249-1262"},"PeriodicalIF":17.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763664","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

An NAD+-dependent metabolic checkpoint regulates hematopoietic stem cell activation and aging 依赖于 NAD+ 的代谢检查点调节造血干细胞的活化和衰老。

IF 17

Nature aging Pub Date : 2024-07-23 DOI: 10.1038/s43587-024-00670-8

Zehan Song, Sang Hee Park, Wei-Chieh Mu, Yufan Feng, Chih-Ling Wang, Yifei Wang, Marine Barthez, Ayane Maruichi, Jiayue Guo, Fanghan Yang, Anita Wong Lin, Kartoosh Heydari, Claudia C. S. Chini, Eduardo N. Chini, Cholsoon Jang, Danica Chen

{"title":"An NAD+-dependent metabolic checkpoint regulates hematopoietic stem cell activation and aging","authors":"Zehan Song, Sang Hee Park, Wei-Chieh Mu, Yufan Feng, Chih-Ling Wang, Yifei Wang, Marine Barthez, Ayane Maruichi, Jiayue Guo, Fanghan Yang, Anita Wong Lin, Kartoosh Heydari, Claudia C. S. Chini, Eduardo N. Chini, Cholsoon Jang, Danica Chen","doi":"10.1038/s43587-024-00670-8","DOIUrl":"10.1038/s43587-024-00670-8","url":null,"abstract":"How hematopoietic stem cells (HSCs) maintain metabolic homeostasis to support tissue repair and regeneration throughout the lifespan is elusive. Here, we show that CD38, an NAD+-dependent metabolic enzyme, promotes HSC proliferation by inducing mitochondrial Ca2+ influx and mitochondrial metabolism in young mice. Conversely, aberrant CD38 upregulation during aging is a driver of HSC deterioration in aged mice due to dysregulated NAD+ metabolism and compromised mitochondrial stress management. The mitochondrial calcium uniporter, a mediator of mitochondrial Ca2+ influx, also supports HSC proliferation in young mice yet drives HSC decline in aged mice. Pharmacological inactivation of CD38 reverses HSC aging and the pathophysiological changes of the aging hematopoietic system in aged mice. Together, our study highlights an NAD+ metabolic checkpoint that balances mitochondrial activation to support HSC proliferation and mitochondrial stress management to enhance HSC self-renewal throughout the lifespan, and links aberrant Ca2+ signaling to HSC aging. Song et al. show that in young mice CD38 supports hematopoietic stem cell (HSC) proliferation by regulating Ca2+ signaling and mitochondrial activity. Conversely, the upregulation of CD38 during aging causes dysregulation of NAD metabolism, mitochondrial stress and HSC dysfunction.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1384-1393"},"PeriodicalIF":17.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753714","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

Long-term cognitive change after COVID-19 in older individuals 老年人服用 COVID-19 后的长期认知变化。

IF 17

Nature aging Pub Date : 2024-07-23 DOI: 10.1038/s43587-024-00687-z

引用次数: 0

Demystifying the appeal process 揭开上诉程序的神秘面纱。

IF 17

Nature aging Pub Date : 2024-07-19 DOI: 10.1038/s43587-024-00679-z

引用次数: 0

A metabolic atlas of blood cells in young and aged mice identifies uridine as a metabolite to rejuvenate aged hematopoietic stem cells 年轻和衰老小鼠血细胞代谢图谱发现尿苷是使衰老造血干细胞恢复活力的代谢物。

IF 17

Nature aging Pub Date : 2024-07-17 DOI: 10.1038/s43587-024-00669-1

Xiangjun Zeng, Ce Shi, Yingli Han, Kejia Hu, Xiaoqing Li, Cong Wei, Lijuan Ding, Jiazhen Cui, Simao Huang, Yulin Xu, Meng Zhang, Wei Shan, Qian Luo, Jian Yu, Zhongzheng Zheng, Xia Li, Pengxu Qian, He Huang

{"title":"A metabolic atlas of blood cells in young and aged mice identifies uridine as a metabolite to rejuvenate aged hematopoietic stem cells","authors":"Xiangjun Zeng, Ce Shi, Yingli Han, Kejia Hu, Xiaoqing Li, Cong Wei, Lijuan Ding, Jiazhen Cui, Simao Huang, Yulin Xu, Meng Zhang, Wei Shan, Qian Luo, Jian Yu, Zhongzheng Zheng, Xia Li, Pengxu Qian, He Huang","doi":"10.1038/s43587-024-00669-1","DOIUrl":"10.1038/s43587-024-00669-1","url":null,"abstract":"Aging of hematopoietic stem cells (HSCs) is accompanied by impaired self-renewal ability, myeloid skewing, immunodeficiencies and increased susceptibility to malignancies. Although previous studies highlighted the pivotal roles of individual metabolites in hematopoiesis, comprehensive and high-resolution metabolomic profiles of different hematopoietic cells across ages are still lacking. In this study, we created a metabolome atlas of different blood cells across ages in mice. We reveal here that purine, pyrimidine and retinol metabolism are enriched in young hematopoietic stem and progenitor cells (HSPCs), whereas glutamate and sphingolipid metabolism are concentrated in aged HSPCs. Through metabolic screening, we identified uridine as a potential regulator to rejuvenate aged HSPCs. Mechanistically, uridine treatment upregulates the FoxO signaling pathway and enhances self-renewal while suppressing inflammation in aged HSCs. Finally, we constructed an open-source platform for public easy access and metabolomic analysis in blood cells. Collectively, we provide a resource for metabolic studies in hematopoiesis that can contribute to future anti-aging metabolite screening. Zeng, Shi, Han, Hu, Li, Wei et al. present a metabolic atlas covering 15 hematopoietic cell types from young and aged mice. By screening metabolites that are depleted with age, they identify that uridine treatment can restore function in aged hematopoietic stem cells.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1477-1492"},"PeriodicalIF":17.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636320","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