Nature aging最新文献_第8页

Perspectives on biomarkers of reproductive aging for fertility and beyond 生殖老化生物标志物对生育及其他问题的展望

IF 17

Nature aging Pub Date : 2024-12-13 DOI: 10.1038/s43587-024-00770-5

Si Wang, Jie Ren, Ying Jing, Jing Qu, Guang-Hui Liu

{"title":"Perspectives on biomarkers of reproductive aging for fertility and beyond","authors":"Si Wang, Jie Ren, Ying Jing, Jing Qu, Guang-Hui Liu","doi":"10.1038/s43587-024-00770-5","DOIUrl":"10.1038/s43587-024-00770-5","url":null,"abstract":"Reproductive aging, spanning an age-related functional decline in the female and male reproductive systems, compromises fertility and leads to a range of health complications. In this Perspective, we first introduce a comprehensive framework for biomarkers applicable in clinical settings and discuss the existing repertoire of biomarkers used in practice. These encompass functional, imaging-based and biofluid-based biomarkers, all of which reflect the physiological characteristics of reproductive aging and help to determine the reproductive biological age. Next, we delve into the molecular alterations associated with aging in the reproductive system, highlighting the gap between these changes and their potential as biomarkers. Finally, to enhance the precision and practicality of assessing reproductive aging, we suggest adopting cutting-edge technologies for identifying new biomarkers and conducting thorough validations in population studies before clinical applications. These advancements will foster improved comprehension, prognosis and treatment of subfertility, thereby increasing chances of preserving reproductive health and resilience in populations of advanced age. Measuring reproductive aging in humans remains challenging. In this Perspective, Wang et al. summarize biomarkers for reproductive aging in clinical use, discuss age-linked molecular changes related to reproductive aging that could potentially serve as future biomarkers and highlight unresolved challenges and upcoming opportunities in the field.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 12","pages":"1697-1710"},"PeriodicalIF":17.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821517","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

Challenges for aging research in Lebanon in times of crisis and conflict 危机和冲突时期黎巴嫩老龄化研究面临的挑战。

IF 17

Nature aging Pub Date : 2024-12-10 DOI: 10.1038/s43587-024-00787-w

Martine Elbejjani, Adina Zeki Al Hazzouri, Kaylie Moropoulos, Abla M. Sibai

引用次数: 0

IL-23R is a senescence-linked circulating and tissue biomarker of aging IL-23R是一种与衰老相关的循环和组织生物标志物。

IF 17

Nature aging Pub Date : 2024-12-10 DOI: 10.1038/s43587-024-00752-7

Chase M. Carver, Sonia L. Rodriguez, Elizabeth J. Atkinson, Andrew J. Dosch, Niels C. Asmussen, Paul T. Gomez, Ethan A. Leitschuh, Jair M. Espindola-Netto, Karthik B. Jeganathan, Madison G. Whaley, Theodore M. Kamenecka, Darren J. Baker, Andrew J. Haak, Nathan K. LeBrasseur, Marissa J. Schafer

{"title":"IL-23R is a senescence-linked circulating and tissue biomarker of aging","authors":"Chase M. Carver, Sonia L. Rodriguez, Elizabeth J. Atkinson, Andrew J. Dosch, Niels C. Asmussen, Paul T. Gomez, Ethan A. Leitschuh, Jair M. Espindola-Netto, Karthik B. Jeganathan, Madison G. Whaley, Theodore M. Kamenecka, Darren J. Baker, Andrew J. Haak, Nathan K. LeBrasseur, Marissa J. Schafer","doi":"10.1038/s43587-024-00752-7","DOIUrl":"10.1038/s43587-024-00752-7","url":null,"abstract":"Cellular senescence is an aging mechanism characterized by cell cycle arrest and a senescence-associated secretory phenotype (SASP). Preclinical studies demonstrate that senolytic drugs, which target survival pathways in senescent cells, can counteract age-associated conditions that span several organs. The comparative efficacy of distinct senolytic drugs for modifying aging and senescence biomarkers in vivo has not been demonstrated. Here, we established aging- and senescence-related plasma proteins and tissue transcripts that changed in old versus young female and male mice. We investigated responsivity to acute treatment with venetoclax, navitoclax, fisetin or luteolin versus transgenic senescent cell clearance in aged p16-InkAttac mice. We discovered that age-dependent changes in plasma proteins, including IL-23R, CCL5 and CA13, were reversed by senotherapeutics, which corresponded to expression differences in tissues, particularly in the kidney. In plasma from humans across the lifespan, IL-23R increased with age. Our results reveal circulating factors as candidate mediators of senescence-associated interorgan signal transduction and translationally impactful biomarkers of systemic senescent cell burden. Using mouse and human plasma, Carver et al. identify factors that are altered with age and test which are reverted by a panel of genetic and pharmacological senolytic interventions in aged mice. They identify IL-23R as a senescence-associated, age-increased circulating biomarker.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 2","pages":"291-305"},"PeriodicalIF":17.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00752-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808846","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

Plasma proteomics identify biomarkers and undulating changes of brain aging 血浆蛋白质组学确定了大脑衰老的生物标志物和起伏变化。

IF 17

Nature aging Pub Date : 2024-12-09 DOI: 10.1038/s43587-024-00753-6

Wei-Shi Liu, Jia You, Shi-Dong Chen, Yi Zhang, Jian-Feng Feng, Yu-Ming Xu, Jin-Tai Yu, Wei Cheng

{"title":"Plasma proteomics identify biomarkers and undulating changes of brain aging","authors":"Wei-Shi Liu, Jia You, Shi-Dong Chen, Yi Zhang, Jian-Feng Feng, Yu-Ming Xu, Jin-Tai Yu, Wei Cheng","doi":"10.1038/s43587-024-00753-6","DOIUrl":"10.1038/s43587-024-00753-6","url":null,"abstract":"Proteomics enables the characterization of brain aging biomarkers and discernment of changes during brain aging. We leveraged multimodal brain imaging data from 10,949 healthy adults to estimate brain age gap (BAG), an indicator of brain aging. Proteome-wide association analysis across 4,696 participants of 2,922 proteins identified 13 significantly associated with BAG, implicating stress, regeneration and inflammation. Brevican (BCAN) (β = −0.838, P = 2.63 × 10−10) and growth differentiation factor 15 (β = 0.825, P = 3.48 × 10−11) showed the most significant, and multiple, associations with dementia, stroke and movement functions. Dysregulation of BCAN affected multiple cortical and subcortical structures. Mendelian randomization supported the causal association between BCAN and BAG. We revealed undulating changes in the plasma proteome across brain aging, and profiled brain age-related change peaks at 57, 70 and 78 years, implicating distinct biological pathways during brain aging. Our findings revealed the plasma proteomic landscape of brain aging and pinpointed biomarkers for brain disorders. Using proteomics and imaging data from UK Biobank, the authors identified multiple circulating proteins associated with brain aging and discovered undulating age-related changes in the plasma proteome, with peaks occurring at 57, 70 and 78 years of age.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 1","pages":"99-112"},"PeriodicalIF":17.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803897","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

Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions 绘制老年人大脑中的microRNA景观及其对神经精神疾病的遗传贡献。

IF 17

Nature aging Pub Date : 2024-12-06 DOI: 10.1038/s43587-024-00778-x

Selina M. Vattathil, Ekaterina S. Gerasimov, Se Min Canon, Adriana Lori, Sarah Sze Min Tan, Paul J. Kim, Yue Liu, Eric C. Lai, David A. Bennett, Thomas S. Wingo, Aliza P. Wingo

{"title":"Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions","authors":"Selina M. Vattathil, Ekaterina S. Gerasimov, Se Min Canon, Adriana Lori, Sarah Sze Min Tan, Paul J. Kim, Yue Liu, Eric C. Lai, David A. Bennett, Thomas S. Wingo, Aliza P. Wingo","doi":"10.1038/s43587-024-00778-x","DOIUrl":"10.1038/s43587-024-00778-x","url":null,"abstract":"MicroRNAs (miRNAs) play a crucial role in regulating gene expression and influence many biological processes. Despite their importance, understanding of how genetic variation affects miRNA expression in the brain and how this relates to brain disorders remains limited. Here we investigated these questions by identifying microRNA expression quantitative trait loci (miR-QTLs), or genetic variants associated with brain miRNA levels, using genome-wide small RNA sequencing profiles from dorsolateral prefrontal cortex samples of 604 older adult donors of European ancestry. Here we show that nearly half (224 of 470) of the analyzed miRNAs have associated miR-QTLs, many of which fall in regulatory regions such as brain promoters and enhancers. We also demonstrate that intragenic miRNAs often have genetic regulation independent from their host genes. Furthermore, by integrating our findings with 16 genome-wide association studies of psychiatric and neurodegenerative disorders, we identified miRNAs that likely contribute to bipolar disorder, depression, schizophrenia and Parkinson’s disease. These findings advance understanding of the genetic regulation of miRNAs and their role in brain health and disease. Using small RNA sequencing data from aged human brain tissue, Vattathil, Gerasimov et al. uncovered genetic variants that influence microRNA (miRNA) expression and, by integrating genome-wide association study data, identified miRNAs linked to the etiology of psychiatric and neurodegenerative disorders.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 2","pages":"306-319"},"PeriodicalIF":17.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00778-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793029","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

Age-related changes in mammary gland increase tumorigenesis 年龄相关的乳腺变化会增加肿瘤的发生。

IF 17

Nature aging Pub Date : 2024-12-05 DOI: 10.1038/s43587-024-00783-0

Anna Kriebs

引用次数: 0

Age as an ingredient of household food waste 年龄是家庭食物垃圾的一个组成部分。

IF 17

Nature aging Pub Date : 2024-12-04 DOI: 10.1038/s43587-024-00784-z

George Andrew S. Inglis

引用次数: 0

Discovering geroprotectors through the explainable artificial intelligence-based platform AgeXtend 通过可解释的人工智能平台AgeXtend发现老年保护器。

IF 17

Nature aging Pub Date : 2024-12-03 DOI: 10.1038/s43587-024-00763-4

Sakshi Arora, Aayushi Mittal, Subhadeep Duari, Sonam Chauhan, Nilesh Kumar Dixit, Sanjay Kumar Mohanty, Arushi Sharma, Saveena Solanki, Anmol Kumar Sharma, Vishakha Gautam, Pushpendra Singh Gahlot, Shiva Satija, Jeet Nanshi, Nikita Kapoor, Lavanya CB, Debarka Sengupta, Parul Mehrotra, Tarini Shankar Ghosh, Gaurav Ahuja

{"title":"Discovering geroprotectors through the explainable artificial intelligence-based platform AgeXtend","authors":"Sakshi Arora, Aayushi Mittal, Subhadeep Duari, Sonam Chauhan, Nilesh Kumar Dixit, Sanjay Kumar Mohanty, Arushi Sharma, Saveena Solanki, Anmol Kumar Sharma, Vishakha Gautam, Pushpendra Singh Gahlot, Shiva Satija, Jeet Nanshi, Nikita Kapoor, Lavanya CB, Debarka Sengupta, Parul Mehrotra, Tarini Shankar Ghosh, Gaurav Ahuja","doi":"10.1038/s43587-024-00763-4","DOIUrl":"10.1038/s43587-024-00763-4","url":null,"abstract":"Aging involves metabolic changes that lead to reduced cellular fitness, yet the role of many metabolites in aging is unclear. Understanding the mechanisms of known geroprotective molecules reveals insights into metabolic networks regulating aging and aids in identifying additional geroprotectors. Here we present AgeXtend, an artificial intelligence (AI)-based multimodal geroprotector prediction platform that leverages bioactivity data of known geroprotectors. AgeXtend encompasses modules that predict geroprotective potential, assess toxicity and identify target proteins and potential mechanisms. We found that AgeXtend accurately identified the pro-longevity effects of known geroprotectors excluded from training data, such as metformin and taurine. Using AgeXtend, we screened ~1.1 billion compounds and identified numerous potential geroprotectors, which we validated using yeast and Caenorhabditis elegans lifespan assays, as well as exploring microbiome-derived metabolites. Finally, we evaluated endogenous metabolites predicted as senomodulators using senescence assays in human fibroblasts, highlighting AgeXtend’s potential to reveal unidentified geroprotectors and provide insights into aging mechanisms. Arora et al. present AgeXtend, an explainable artificial intelligence-based platform that leverages bioactivity data to predict geroprotectors. They validate potential geroprotectors identified using this platform in yeast, worm and senescence assays.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 1","pages":"144-161"},"PeriodicalIF":17.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776115","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 chimeric peptide promotes immune surveillance of senescent cells in injury, fibrosis, tumorigenesis and aging 嵌合肽促进损伤，纤维化，肿瘤发生和衰老衰老细胞的免疫监视。

IF 17

Nature aging Pub Date : 2024-12-02 DOI: 10.1038/s43587-024-00750-9

Xinliang Ming, Ze Yang, Yuqiao Huang, Zhiguo Wang, Qingyan Zhang, Changchang Lu, Yandi Sun, Yuanhao Chen, Liang Zhang, Jicheng Wu, Hao Shou, Zhimin Lu, Ben Wang

{"title":"A chimeric peptide promotes immune surveillance of senescent cells in injury, fibrosis, tumorigenesis and aging","authors":"Xinliang Ming, Ze Yang, Yuqiao Huang, Zhiguo Wang, Qingyan Zhang, Changchang Lu, Yandi Sun, Yuanhao Chen, Liang Zhang, Jicheng Wu, Hao Shou, Zhimin Lu, Ben Wang","doi":"10.1038/s43587-024-00750-9","DOIUrl":"10.1038/s43587-024-00750-9","url":null,"abstract":"The accumulation of senescent cells can lead to tissue degeneration, chronic inflammatory disease and age-related tumorigenesis. Interventions such as senolytics are currently limited by off-target toxicity, which could be circumvented by instead enhancing immune-mediated senescent cell clearance; however, immune surveillance of senescent cells is often impeded by immunosuppressive factors in the inflammatory microenvironment. Here, we employ a chimeric peptide as a ‘matchmaker’ to bind to the urokinase-type plasminogen activator receptor, a cell surface marker of senescent cells. This peptide modifies the cell surface with polyglutamic acid, promoting immune cell-mediated responses through glutamate recognition. By enhancing the recruitment of immune cells and directly coupling senescent cells and immune cells, we show that this chimeric peptide induces immune clearance of senescent cells and restores tissue homeostasis in conditions such as liver fibrosis, lung injury, cancer and natural aging in mice. This chimeric peptide introduces an immunological conversion strategy that rebalances the senescent immune microenvironment, offering a promising direction for aging immunotherapy. Ming, Yang, Huang et al. design a chimeric matchmaker peptide, which targets a senescent cell-specific surface marker and modifies the cell surface with polyglutamic acid. This promotes interactions with natural killer cells and senescent cell clearance in liver fibrosis, lung injury, cancer and natural aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 1","pages":"28-47"},"PeriodicalIF":17.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776114","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

Keeping endogenous retroviruses at bay 抑制内源性逆转录病毒。

IF 17

Nature aging Pub Date : 2024-11-29 DOI: 10.1038/s43587-024-00785-y

Hannah Walters

引用次数: 0