Nature aging最新文献

{"title":"Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing.","authors":"Nathan S Gasek, Pengyi Yan, Junyu Zhu, K-Raman Purushothaman, Taewan Kim, Lichao Wang, Binsheng Wang, William F Flynn, Mingda Sun, Chun Guo, Billy Huggins, Roshanak Sharafieh, Yueying Zhou, Vojtech Parizek, Tamar Tchkonia, James L Kirkland, Saranya P Wyles, Ming Xu","doi":"10.1038/s43587-024-00755-4","DOIUrl":"https://doi.org/10.1038/s43587-024-00755-4","url":null,"abstract":"<p><p>While senescent cells have detrimental roles in several contexts, they are highly heterogeneous. p16 highly expressing senescent cells have been reported to exert beneficial functions in wound healing. Here we use Xenium spatial transcriptomics to identify a distinct p21 highly expressing senescent population induced on wounding, with a pro-inflammatory profile. We find that clearing p21 highly expressing cells expedites wound closure and is partially mediated by NF-κB inhibition, thus enhancing our understanding of the multifaceted functions of senescence in tissue remodeling.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634961","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}

{"title":"Diagnosis of Alzheimer’s disease using plasma biomarkers adjusted to clinical probability","authors":"Joseph Therriault,&nbsp;Shorena Janelidze,&nbsp;Andréa Lessa Benedet,&nbsp;Nicholas J. Ashton,&nbsp;Javier Arranz Martínez,&nbsp;Armand Gonzalez-Escalante,&nbsp;Bruna Bellaver,&nbsp;Daniel Alcolea,&nbsp;Agathe Vrillon,&nbsp;Helmet Karim,&nbsp;Michelle M. Mielke,&nbsp;Chang Hyung Hong,&nbsp;Hyun Woong Roh,&nbsp;José Contador,&nbsp;Albert Puig Pijoan,&nbsp;Alicia Algeciras-Schimnich,&nbsp;Prashanthi Vemuri,&nbsp;Jonathan Graff-Radford,&nbsp;Val J. Lowe,&nbsp;Thomas K. Karikari,&nbsp;Erin Jonaitis,&nbsp;Wagner Brum,&nbsp;Cécile Tissot,&nbsp;Stijn Servaes,&nbsp;Nesrine Rahmouni,&nbsp;Arthur C. Macedo,&nbsp;Jenna Stevenson,&nbsp;Jaime Fernandez-Arias,&nbsp;Yi-Ting Wang,&nbsp;Marcel S. Woo,&nbsp;Manuel A. Friese,&nbsp;Wan Lu Jia,&nbsp;Julien Dumurgier,&nbsp;Claire Hourregue,&nbsp;Emmanuel Cognat,&nbsp;Pamela Lukasewicz Ferreira,&nbsp;Paolo Vitali,&nbsp;Sterling Johnson,&nbsp;Tharick A. Pascoal,&nbsp;Serge Gauthier,&nbsp;Alberto Lleó,&nbsp;Claire Paquet,&nbsp;Ronald C. Petersen,&nbsp;David Salmon,&nbsp;Niklas Mattsson-Carlgren,&nbsp;Sebastian Palmqvist,&nbsp;Erik Stomrud,&nbsp;Douglas Galasko,&nbsp;Sang Joon Son,&nbsp;Henrik Zetterberg,&nbsp;Juan Fortea,&nbsp;Marc Suárez-Calvet,&nbsp;Clifford R. Jack Jr,&nbsp;Kaj Blennow,&nbsp;Oskar Hansson,&nbsp;Pedro Rosa-Neto","doi":"10.1038/s43587-024-00731-y","DOIUrl":"10.1038/s43587-024-00731-y","url":null,"abstract":"Recently approved anti-amyloid immunotherapies for Alzheimer’s disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the circumstances requiring confirmatory testing are poorly understood. Individual-level interpretation of diagnostic test results requires knowledge of disease prevalence in relation to clinical presentation (clinical pretest probability). Here, in a study of 6,896 individuals evaluated from 11 cohort studies from six countries, we determined the positive and negative predictive value of five plasma biomarkers for amyloid-β pathology in cognitively impaired individuals in relation to clinical pretest probability. We observed that p-tau217 could rule in amyloid-β pathology in individuals with probable AD dementia (positive predictive value above 95%). In mild cognitive impairment, p-tau217 interpretation depended on patient age. Negative p-tau217 results could rule out amyloid-β pathology in individuals with non-AD dementia syndromes (negative predictive value between 90% and 99%). Our findings provide a framework for the individual-level interpretation of plasma biomarkers, suggesting that p-tau217 combined with clinical phenotyping can identify patients where amyloid-β pathology can be ruled in or out without the need for PET or CSF confirmatory testing. Therriault et al. provide a framework for the individual-level interpretation of plasma biomarkers by determining their positive and negative predictive values for amyloid positron emission tomography status in relation to patient age and clinical symptoms.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 11","pages":"1529-1537"},"PeriodicalIF":17.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00731-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635093","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}

{"title":"Chronic social stress induces p16-mediated senescent cell accumulation in mice.","authors":"Carey E Lyons, Jean Pierre Pallais, Seth McGonigle, Rachel P Mansk, Charles W Collinge, Matthew J Yousefzadeh, Darren J Baker, Patricia R Schrank, Jesse W Williams, Laura J Niedernhofer, Jan M van Deursen, Maria Razzoli, Alessandro Bartolomucci","doi":"10.1038/s43587-024-00743-8","DOIUrl":"https://doi.org/10.1038/s43587-024-00743-8","url":null,"abstract":"<p><p>Life stress can shorten lifespan and increase risk for aging-related diseases, but the biology underlying this phenomenon remains unclear. Here we assessed the effect of chronic stress on cellular senescence-a hallmark of aging. Exposure to restraint stress, a psychological non-social stress model, increased p21^Cip1 exclusively in the brains of male, but not female mice, and in a p16^Ink4a-independent manner. Conversely, exposure to chronic subordination stress (only males were tested) increased key senescent cell markers in peripheral blood mononuclear cells, adipose tissue and brain, in a p16^Ink4a-dependent manner. p16^Ink4a-positive cells in the brain of chronic subordination stress-exposed mice were primarily hippocampal and cortical neurons with evidence of DNA damage that could be reduced by p16^Ink4a cell clearance. Clearance of p16^Ink4a-positive cells was not sufficient to ameliorate the adverse effects of social stress on measured metrics of healthspan. Overall, our findings indicate that social stress induces an organ-specific and p16^Ink4a-dependent accumulation of senescent cells, illuminating a fundamental way by which the social environment can contribute to aging.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634960","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}

{"title":"Cell type-divergent functions of senescence","authors":"Hannah Walters","doi":"10.1038/s43587-024-00764-3","DOIUrl":"10.1038/s43587-024-00764-3","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 11","pages":"1520-1520"},"PeriodicalIF":17.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634981","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}

{"title":"Modifiable risk factors of dementia in Latin America","authors":"Yahyah Aman","doi":"10.1038/s43587-024-00766-1","DOIUrl":"10.1038/s43587-024-00766-1","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 11","pages":"1521-1521"},"PeriodicalIF":17.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607403","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}

{"title":"Phenome-wide associations of human aging uncover sex-specific dynamics","authors":"Lee Reicher,&nbsp;Noam Bar,&nbsp;Anastasia Godneva,&nbsp;Yotam Reisner,&nbsp;Liron Zahavi,&nbsp;Nir Shahaf,&nbsp;Raja Dhir,&nbsp;Adina Weinberger,&nbsp;Eran Segal","doi":"10.1038/s43587-024-00734-9","DOIUrl":"10.1038/s43587-024-00734-9","url":null,"abstract":"Aging varies significantly among individuals of the same chronological age, indicating that biological age (BA), estimated from molecular and physiological biomarkers, may better reflect aging. Prior research has often ignored sex-specific differences in aging patterns and mainly focused on aging biomarkers from a single data modality. Here we analyze a deeply phenotyped longitudinal cohort (10K project, Israel) of 10,000 healthy individuals aged 40–70 years that includes clinical, physiological, behavioral, environmental and multiomic parameters. Follow-up visits are scheduled every 2 years for a total of 25 years. We devised machine learning models of chronological age and computed biological aging scores that represented diverse physiological systems, revealing different aging patterns among sexes. Higher BA scores were associated with a higher prevalence of age-related medical conditions, highlighting the clinical relevance of these scores. Our analysis revealed system-specific aging dynamics and the potential of deeply phenotyped cohorts to accelerate improvements in our understanding of chronic diseases. Our findings present a more holistic view of the aging process, and lay the foundation for personalized medical prevention strategies. The authors analyzed data from a deeply phenotyped longitudinal cohort to uncover sex-specific aging patterns. They found that biological age scores, derived from diverse biomarkers, correlate with age-related diseases, providing insights for personalized medical interventions.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 11","pages":"1643-1655"},"PeriodicalIF":17.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584538","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}

{"title":"Lessons from the HEALEY adaptive platform trial in amyotrophic lateral sclerosis","authors":"Sabrina Paganoni,&nbsp;Brittney Harkey,&nbsp;Elisa Giacomelli,&nbsp;Merit Cudkowicz,&nbsp;on behalf of the HEALEY ALS Platform Trial Study Group","doi":"10.1038/s43587-024-00740-x","DOIUrl":"10.1038/s43587-024-00740-x","url":null,"abstract":"Platform trials present potential advantages over stand-alone clinical trials. Here, we describe the operational framework of the HEALEY Amyotrophic Lateral Sclerosis Platform Trial, which enables an adaptable operational infrastructure, concurrent enrolment into four distinct regimens and an accelerated start-up time for a new regimen added after initial trial launch.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 11","pages":"1512-1515"},"PeriodicalIF":17.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564637","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}

{"title":"Rejuvenating older neural stem cells","authors":"George Andrew S. Inglis","doi":"10.1038/s43587-024-00761-6","DOIUrl":"10.1038/s43587-024-00761-6","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 11","pages":"1519-1519"},"PeriodicalIF":17.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559895","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}

{"title":"Retraction Note: KDM4 orchestrates epigenomic remodeling of senescent cells and potentiates the senescence-associated secretory phenotype.","authors":"Boyi Zhang, Qilai Long, Shanshan Wu, Qixia Xu, Shuling Song, Liu Han, Min Qian, Xiaohui Ren, Hanxin Liu, Jing Jiang, Jianming Guo, Xiaoling Zhang, Xing Chang, Qiang Fu, Eric W-F Lam, Judith Campisi, James L Kirkland, Yu Sun","doi":"10.1038/s43587-024-00749-2","DOIUrl":"https://doi.org/10.1038/s43587-024-00749-2","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559896","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}

{"title":"The foam cell-derived exosomal miRNA Novel-3 drives neuroinflammation and ferroptosis during ischemic stroke.","authors":"Chuan Qin, Ming-Hao Dong, Yue Tang, Yun-Hui Chu, Luo-Qi Zhou, Hang Zhang, Sheng Yang, Lu-Yang Zhang, Xiao-Wei Pang, Li-Fang Zhu, Wei Wang, Dai-Shi Tian","doi":"10.1038/s43587-024-00727-8","DOIUrl":"https://doi.org/10.1038/s43587-024-00727-8","url":null,"abstract":"<p><p>Large artery atherosclerosis (LAA) is a prevalent cause of acute ischemic stroke (AIS). Understanding the mechanisms linking atherosclerosis to stroke is essential for developing appropriate intervention strategies. Here, we found that the exosomal miRNA Novel-3 is selectively upregulated in the plasma of patients with LAA-AIS. Notably, Novel-3 was predominantly expressed in macrophage-derived foam cells, and its expression correlated with atherosclerotic plaque vulnerability in patients undergoing carotid endarterectomy. Exploring the function of Novel-3 in a mouse model of cerebral ischemia, we found that Novel-3 exacerbated ischemic injury and targeted microglia and macrophages expressing ionized calcium-binding adapter molecule 1 in peri-infarct regions. Mechanistically, Novel-3 increased ferroptosis and neuroinflammation by interacting with striatin (STRN) and downregulating the phosphoinositide 3-kinase-AKT-mechanistic target of rapamycin signaling pathway. Blocking Novel-3 activity or overexpressing STRN provided neuroprotection under ischemic conditions. Our findings suggest that exosomal Novel-3, which is primarily derived from macrophage-derived foam cells, targets microglia and macrophages in the brain to induce neuroinflammation and could serve as a potential therapeutic target for patients with stroke who have atherosclerosis.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142524008","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}