Nature aging最新文献_第2页

A blood-based DNA damage signature in patients with Parkinson's disease is associated with disease progression. 帕金森病患者的血液DNA损伤特征与疾病进展有关。

IF 19.4

Nature aging Pub Date : 2025-09-05 DOI: 10.1038/s43587-025-00926-x

Daisy Sproviero, César Payán-Gómez, Chiara Milanese, Sander Barnhoorn, Shixiang Sun, Akos Gyenis, Domenico Delia, Tammaryn Lashley, Jan H J Hoeijmakers, Jan Vijg, Pier G Mastroberardino

{"title":"A blood-based DNA damage signature in patients with Parkinson's disease is associated with disease progression.","authors":"Daisy Sproviero, César Payán-Gómez, Chiara Milanese, Sander Barnhoorn, Shixiang Sun, Akos Gyenis, Domenico Delia, Tammaryn Lashley, Jan H J Hoeijmakers, Jan Vijg, Pier G Mastroberardino","doi":"10.1038/s43587-025-00926-x","DOIUrl":"https://doi.org/10.1038/s43587-025-00926-x","url":null,"abstract":"Aging is the main risk factor for Parkinson's disease (PD), yet our understanding of how age-related mechanisms contribute to PD pathophysiology remains limited. We conducted a longitudinal analysis of blood samples from the Parkinson's Progression Markers Initiative cohort to investigate DNA damage in PD. Patients with PD exhibited disrupted DNA repair pathways and biased suppression of longer transcripts, indicating age-related, transcription-stalling DNA damage. Notably, at the intake visit, this DNA damage signature was detected only in patients with more severe progression of motor symptoms over 3 years, suggesting its potential as a predictor of disease severity. We validated this signature in independent PD cohorts and confirmed increased DNA damage in peripheral blood cells and dopamine neurons of the substantia nigra pars compacta in postmortem PD brains. Our study sheds light on an aging-related mechanism in PD pathogenesis and identifies potential markers of disease progression, providing a diagnostic platform to prognosticate disease progression.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006939","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

Midlife hearing loss and dementia risk. 中年听力损失和痴呆风险。

IF 19.4

Nature aging Pub Date : 2025-09-03 DOI: 10.1038/s43587-025-00955-6

Nicholas S Reed, Alison R Huang, Josef Coresh

引用次数: 0

The aging factor EPS8 induces disease-related protein aggregation through RAC signaling hyperactivation. 衰老因子EPS8通过RAC信号超激活诱导疾病相关蛋白聚集。

IF 19.4

Nature aging Pub Date : 2025-09-03 DOI: 10.1038/s43587-025-00943-w

Seda Koyuncu, Yaiza Dominguez-Canterla, Rafael Alis, Nassima Salarzai, Dunja Petrovic, Nuria Flames, David Vilchez

{"title":"The aging factor EPS8 induces disease-related protein aggregation through RAC signaling hyperactivation.","authors":"Seda Koyuncu, Yaiza Dominguez-Canterla, Rafael Alis, Nassima Salarzai, Dunja Petrovic, Nuria Flames, David Vilchez","doi":"10.1038/s43587-025-00943-w","DOIUrl":"https://doi.org/10.1038/s43587-025-00943-w","url":null,"abstract":"Aging is a major risk factor for neurodegenerative diseases associated with protein aggregation, including Huntington's disease and amyotrophic lateral sclerosis (ALS). Although these diseases involve different aggregation-prone proteins, their common late onset suggests a link to converging changes resulting from aging. In this study, we found that age-associated hyperactivation of EPS8/RAC signaling in Caenorhabditis elegans promotes the pathological aggregation of Huntington's disease-related polyglutamine repeats and ALS-associated mutant FUS and TDP-43 variants. Conversely, knockdown of eps-8 or RAC orthologs prevents protein aggregation and subsequent deficits in neuronal function during aging. Similarly, inhibiting EPS8 signaling reduces protein aggregation and neurodegeneration in human cell models. We further identify the deubiquitinating enzyme USP4 as a regulator of EPS8 ubiquitination and degradation in both worms and human cells. Notably, reducing USP-4 upregulation during aging prevents EPS-8 accumulation, extends longevity and attenuates disease-related changes. Our findings suggest that targeting EPS8 and its regulatory mechanisms could provide therapeutic strategies for age-related diseases.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994960","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

Nerve-associated macrophages control adipose homeostasis across lifespan and restrain age-related inflammation. 神经相关巨噬细胞在整个生命周期中控制脂肪稳态并抑制与年龄相关的炎症。

IF 19.4

Nature aging Pub Date : 2025-09-02 DOI: 10.1038/s43587-025-00952-9

Elsie Gonzalez-Hurtado, Claire Leveau, Keyi Li, Manish Mishra, Rihao Qu, Emily L Goldberg, Sviatoslav Sidorov, Payal Damani-Yokota, Stephen T Yeung, Camille Khairallah, David Gonzalez, Taverlyn M Shepard, Christina Camell, Maxim N Artyomov, Yuval Kluger, Kamal M Khanna, Vishwa Deep Dixit

{"title":"Nerve-associated macrophages control adipose homeostasis across lifespan and restrain age-related inflammation.","authors":"Elsie Gonzalez-Hurtado, Claire Leveau, Keyi Li, Manish Mishra, Rihao Qu, Emily L Goldberg, Sviatoslav Sidorov, Payal Damani-Yokota, Stephen T Yeung, Camille Khairallah, David Gonzalez, Taverlyn M Shepard, Christina Camell, Maxim N Artyomov, Yuval Kluger, Kamal M Khanna, Vishwa Deep Dixit","doi":"10.1038/s43587-025-00952-9","DOIUrl":"10.1038/s43587-025-00952-9","url":null,"abstract":"Age-related inflammation or 'inflammaging' increases disease burden and controls lifespan. Adipose tissue macrophages (ATMs) are critical regulators of inflammaging; however, the mechanisms involved are not well understood in part because the molecular identities of niche-specific ATMs are unknown. Using intravascular labeling to exclude circulating myeloid cells followed by single-cell sequencing with orthogonal validation via multiparametric flow cytometry, we define sex-specific changes and diverse populations of resident ATMs through lifespan in mice. Aging led to depletion of vessel-associated macrophages, expansion of lipid-associated macrophages and emergence of a unique subset of CD38+ age-associated macrophages in visceral adipose tissue with inflammatory phenotype. Notably, CD169+CD11c- ATMs are enriched in a subpopulation of nerve-associated macrophages (NAMs) that declines with age. Depletion of CD169+ NAMs in aged mice increases inflammaging and impairs lipolysis suggesting catecholamine resistance in visceral adipose tissue. Our findings reveal NAMs are a specialized ATM subset that control adipose homeostasis and link inflammation to tissue dysfunction during aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983446","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

REV-ERBα regulates brain NAD⁺ levels and tauopathy via an NFIL3-CD38 axis. rev - erba通过NFIL3-CD38轴调控脑NAD+水平和tau病变。

IF 19.4

Nature aging Pub Date : 2025-09-01 DOI: 10.1038/s43587-025-00950-x

Jiyeon Lee, Ryeonghwa Kang, Sohui Park, Ibrahim O Saliu, Minsoo Son, Jaymie R Voorhees, Julie M Dimitry, Elsa I Quillin, Lauren N Woodie, Brian V Lananna, Li Gan, Young-Ah Goo, Guoyan Zhao, Mitchell A Lazar, Thomas P Burris, Erik S Musiek

{"title":"REV-ERBα regulates brain NAD+ levels and tauopathy via an NFIL3-CD38 axis.","authors":"Jiyeon Lee, Ryeonghwa Kang, Sohui Park, Ibrahim O Saliu, Minsoo Son, Jaymie R Voorhees, Julie M Dimitry, Elsa I Quillin, Lauren N Woodie, Brian V Lananna, Li Gan, Young-Ah Goo, Guoyan Zhao, Mitchell A Lazar, Thomas P Burris, Erik S Musiek","doi":"10.1038/s43587-025-00950-x","DOIUrl":"10.1038/s43587-025-00950-x","url":null,"abstract":"Nicotinamide adenine dinucleotide (NAD+) is a critical metabolic co-enzyme implicated in brain aging, and augmenting NAD+ levels in the aging brain is an attractive therapeutic strategy for neurodegeneration. However, the molecular mechanisms of brain NAD+ regulation are incompletely understood. In cardiac tissue, the circadian nuclear receptor REV-ERBα has been shown to regulate NAD+ via control of the NAD+-producing enzyme NAMPT. Here we show that REV-ERBα controls brain NAD+ levels through a distinct pathway involving NFIL3-dependent suppression of the NAD+-consuming enzyme CD38, particularly in astrocytes. REV-ERBα deletion does not affect NAMPT expression in the brain and has an opposite effect on NAD+ levels as in the heart. Astrocytic REV-ERBα deletion augments brain NAD+ and prevents tauopathy in P301S mice. Our data reveal that REV-ERBα regulates NAD+ in a tissue-specific manner via opposing regulation of NAMPT versus CD38 and define an astrocyte REV-ERBα-NFIL3-CD38 pathway controlling brain NAD+ metabolism and neurodegeneration.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983528","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

Tackling Ghana's dementia underdiagnosis needs investment in workforce, diagnostics, education and insurance. 解决加纳的痴呆症诊断不足问题需要在劳动力、诊断、教育和保险方面进行投资。

IF 19.4

Nature aging Pub Date : 2025-09-01 DOI: 10.1038/s43587-025-00963-6

Mary Amoakoh-Coleman

引用次数: 0

Unlocking longevity through the comparative biology of aging. 通过衰老的比较生物学解开长寿之谜。

IF 19.4

Nature aging Pub Date : 2025-08-28 DOI: 10.1038/s43587-025-00945-8

Cheyenne Rechsteiner, Francesco Morandini, Sei Joong Kim, Andrei Seluanov, Vera Gorbunova

引用次数: 0

Oxidative stress response protein delays ovarian aging by promoting stress granule clearance. 氧化应激反应蛋白通过促进应激颗粒清除延缓卵巢衰老。

IF 19.4

Nature aging Pub Date : 2025-08-27 DOI: 10.1038/s43587-025-00960-9

引用次数: 0

Mevalonate metabolites boost aged oocyte quality through prenylation of small GTPases. 甲羟戊酸代谢物通过小gtp酶的戊烯酰化提高衰老的卵母细胞质量。

IF 19.4

Nature aging Pub Date : 2025-08-26 DOI: 10.1038/s43587-025-00946-7

Chuanming Liu, Huidan Zhang, Jialian Mao, Sainan Zhang, Xiao Tian, Yibing Zhu, Changjiang Wang, Junshun Fang, Huijie Pan, Nannan Kang, Yang Zhang, Jidong Zhou, Xin Zhen, Guijun Yan, Chaojun Li, Yali Hu, Cunqi Ye, Ran Xie, Chun So, Haixiang Sun, Lijun Ding

{"title":"Mevalonate metabolites boost aged oocyte quality through prenylation of small GTPases.","authors":"Chuanming Liu, Huidan Zhang, Jialian Mao, Sainan Zhang, Xiao Tian, Yibing Zhu, Changjiang Wang, Junshun Fang, Huijie Pan, Nannan Kang, Yang Zhang, Jidong Zhou, Xin Zhen, Guijun Yan, Chaojun Li, Yali Hu, Cunqi Ye, Ran Xie, Chun So, Haixiang Sun, Lijun Ding","doi":"10.1038/s43587-025-00946-7","DOIUrl":"https://doi.org/10.1038/s43587-025-00946-7","url":null,"abstract":"Declining oocyte quality is the major contributor to female subfertility in aged mammals. Currently, there are no effective interventions to ameliorate aged oocyte quality. Here we found that oocytes at metaphase I from the cumulus-oocyte complexes of aged mice showed reduced cortical F-actin and lower levels of mevalonate (MVA) pathway metabolites, including MVA, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate. We further showed that MVA supplementation improved FPP levels, cortical F-actin and the quality of aged oocytes. Mechanistically, we found that MVA supplementation induced granulosa cells to synthesize FPP, which was subsequently transferred to aged oocytes. Transported FPP increased the prenylation of small GTPases, including CDC42 and RAC1, and promoted membrane localization of CDC42-N-WASP-Arp2/3 and RAC1-WAVE2-Arp2/3 complexes, promoting cortical F-actin reassembly and reducing aneuploidy of aged oocytes. We also identified a natural chemical compound, 8-isopentenyl flavone, with an isopentenyl side chain from Epimedium brevicornu Maxim, which could increase CDC42 and RAC1 prenylation, improving the cortical F-actin and the competence of aged oocytes, and ameliorating reproductive outcomes in aged female mice. Collectively, increasing the prenylation of small GTPases via MVA metabolites or 8-isopentenyl flavone provides a therapeutic approach for boosting female fertility during reproductive aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983440","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

Plasma tau biomarkers for biological staging of Alzheimer's disease. 血浆tau生物标志物用于阿尔茨海默病的生物学分期。

IF 19.4

Nature aging Pub Date : 2025-08-22 DOI: 10.1038/s43587-025-00951-w

Laia Montoliu-Gaya, Gemma Salvadó, Joseph Therriault, Johanna Nilsson, Shorena Janelidze, Sophia Weiner, Nicholas J Ashton, Andrea L Benedet, Nesrine Rahmouni, Juan Lantero-Rodriguez, Niklas Mattsson-Carlgren, Sebastian Palmqvist, Gunnar Brinkmalm, Erik Stomrud, Henrik Zetterberg, Johan Gobom, Pedro Rosa-Neto, Kaj Blennow, Oskar Hansson

{"title":"Plasma tau biomarkers for biological staging of Alzheimer's disease.","authors":"Laia Montoliu-Gaya, Gemma Salvadó, Joseph Therriault, Johanna Nilsson, Shorena Janelidze, Sophia Weiner, Nicholas J Ashton, Andrea L Benedet, Nesrine Rahmouni, Juan Lantero-Rodriguez, Niklas Mattsson-Carlgren, Sebastian Palmqvist, Gunnar Brinkmalm, Erik Stomrud, Henrik Zetterberg, Johan Gobom, Pedro Rosa-Neto, Kaj Blennow, Oskar Hansson","doi":"10.1038/s43587-025-00951-w","DOIUrl":"https://doi.org/10.1038/s43587-025-00951-w","url":null,"abstract":"A blood biomarker-based staging system for Alzheimer's disease (AD) could improve the diagnosis, prognosis and identification of individuals most likely to benefit from specific therapies. Here, using targeted mass spectrometry, we measured six phosphorylated and six nonphosphorylated tau peptides in plasma from two independent cohorts: BioFINDER-2 and TRIAD (n = 689). We also analyzed the ratios of phosphorylated to nonphosphorylated peptides. Our results revealed that specific tau species became abnormal at different points along the disease continuum. Based on these findings, we developed a data-driven, blood-based staging model that demonstrated strong consistency across cohorts (>85% agreement in ≥90% initializations) and reflected changes in other AD biomarkers. These plasma-based stages were associated with clinical diagnoses, positron emission tomography-based stages and distinct patterns of longitudinal disease progression, including Aβ- and tau-positron emission tomography uptake, atrophy and cognitive decline. This study highlights the potential of tau blood-based biomarkers for biological staging in AD, offering a scalable tool for tracking disease progression and guiding clinical decisions.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983611","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