Nature aging最新文献_第7页

The promise of machine learning approaches to capture cellular senescence heterogeneity 机器学习方法捕捉细胞衰老异质性的前景。

IF 17

Nature aging Pub Date : 2024-08-26 DOI: 10.1038/s43587-024-00703-2

Imanol Duran, Cleo L. Bishop, Jesús Gil, Ryan Wallis

引用次数: 0

Serum proteomics reveal APOE-ε4-dependent and APOE-ε4-independent protein signatures in Alzheimer’s disease 血清蛋白质组学揭示了阿尔茨海默病中依赖 APOE-ε4 和不依赖 APOE-ε4 的蛋白质特征。

IF 17

Nature aging Pub Date : 2024-08-21 DOI: 10.1038/s43587-024-00693-1

Elisabet A. Frick, Valur Emilsson, Thorarinn Jonmundsson, Anna E. Steindorsdottir, Erik C. B. Johnson, Raquel Puerta, Eric B. Dammer, Anantharaman Shantaraman, Amanda Cano, Mercè Boada, Sergi Valero, Pablo García-González, Elias F. Gudmundsson, Alexander Gudjonsson, Rebecca Pitts, Xiazi Qiu, Nancy Finkel, Joseph J. Loureiro, Anthony P. Orth, Nicholas T. Seyfried, Allan I. Levey, Agustin Ruiz, Thor Aspelund, Lori L. Jennings, Lenore J. Launer, Valborg Gudmundsdottir, Vilmundur Gudnason

{"title":"Serum proteomics reveal APOE-ε4-dependent and APOE-ε4-independent protein signatures in Alzheimer’s disease","authors":"Elisabet A. Frick, Valur Emilsson, Thorarinn Jonmundsson, Anna E. Steindorsdottir, Erik C. B. Johnson, Raquel Puerta, Eric B. Dammer, Anantharaman Shantaraman, Amanda Cano, Mercè Boada, Sergi Valero, Pablo García-González, Elias F. Gudmundsson, Alexander Gudjonsson, Rebecca Pitts, Xiazi Qiu, Nancy Finkel, Joseph J. Loureiro, Anthony P. Orth, Nicholas T. Seyfried, Allan I. Levey, Agustin Ruiz, Thor Aspelund, Lori L. Jennings, Lenore J. Launer, Valborg Gudmundsdottir, Vilmundur Gudnason","doi":"10.1038/s43587-024-00693-1","DOIUrl":"10.1038/s43587-024-00693-1","url":null,"abstract":"A deeper understanding of the molecular processes underlying late-onset Alzheimer’s disease (LOAD) could aid in biomarker and drug target discovery. Using high-throughput serum proteomics in the prospective population-based Age, Gene/Environment Susceptibility–Reykjavik Study (AGES) cohort of 5,127 older Icelandic adults (mean age, 76.6 ± 5.6 years), we identified 303 proteins associated with incident LOAD over a median follow-up of 12.8 years. Over 40% of these proteins were associated with LOAD independently of APOE-ε4 carrier status, were implicated in neuronal processes and overlapped with LOAD protein signatures in brain and cerebrospinal fluid. We identified 17 proteins whose associations with LOAD were strongly dependent on APOE-ε4 carrier status, with mostly consistent associations in cerebrospinal fluid. Remarkably, four of these proteins (TBCA, ARL2, S100A13 and IRF6) were downregulated by APOE-ε4 yet upregulated due to LOAD, a finding replicated in external cohorts and possibly reflecting a response to disease onset. These findings highlight dysregulated pathways at the preclinical stages of LOAD, including those both independent of and dependent on APOE-ε4 status. Using high-throughput proteomics in a prospective population-based study of older adults, Frick et al. identified over 300 proteins linked to incident late-onset Alzheimer’s disease, including associations dependent on or independent of APOE-ε4 status.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1446-1464"},"PeriodicalIF":17.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00693-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019980","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

Accelerometer-derived ‘weekend warrior’ physical activity pattern and brain health 加速度计衍生的 "周末战士 "体育活动模式与大脑健康。

IF 17

Nature aging Pub Date : 2024-08-21 DOI: 10.1038/s43587-024-00688-y

Jiahao Min, Zhi Cao, Tingshan Duan, Yaogang Wang, Chenjie Xu

{"title":"Accelerometer-derived ‘weekend warrior’ physical activity pattern and brain health","authors":"Jiahao Min, Zhi Cao, Tingshan Duan, Yaogang Wang, Chenjie Xu","doi":"10.1038/s43587-024-00688-y","DOIUrl":"10.1038/s43587-024-00688-y","url":null,"abstract":"Extensive evidence shows the beneficial effect of adhering to a regular physical activity (PA) pattern on brain health. However, whether the ‘weekend warrior’ pattern, characterized by concentrated moderate-to-vigorous PA (MVPA) over 1–2 days, is associated with brain health is unclear. Here, we perform a prospective cohort study including 75,629 participants from the UK Biobank with validated accelerometry data. Individuals were classified into three PA patterns using current guideline thresholds: inactive (<150 min week−1 of MVPA), weekend warrior (≥150 min week−1 with ≥50% of total MVPA occurring within 1–2 days) and regularly active (≥150 min week−1 but not meeting weekend warrior criteria). We find that the weekend warrior pattern is associated with similarly lower risks of dementia, stroke, Parkinson’s disease, depressive disorders and anxiety compared to a regularly active pattern. Our findings highlight the weekend warrior pattern as a potential alternative in preventive intervention strategies, particularly for those unable to maintain daily activity routines. Research suggests that exercise has a beneficial effect on brain health during aging but more information is needed. Here, the authors show, using UK Biobank data, that the ‘weekend warrior’ physical activity pattern, with concentrated exercise over 1–2 days, is similarly linked to lower risk of brain disorders compared to regular exercise.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1394-1402"},"PeriodicalIF":17.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019979","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

Restoration of cervical lymphatic vessel function in aging rescues cerebrospinal fluid drainage 在衰老过程中恢复颈部淋巴管功能可挽救脑脊液引流。

IF 17

Nature aging Pub Date : 2024-08-15 DOI: 10.1038/s43587-024-00691-3

Ting Du, Aditya Raghunandan, Humberto Mestre, Virginia Plá, Guojun Liu, Antonio Ladrón-de-Guevara, Evan Newbold, Paul Tobin, Daniel Gahn-Martinez, Saurav Pattanayak, Qinwen Huang, Weiguo Peng, Maiken Nedergaard, Douglas H. Kelley

{"title":"Restoration of cervical lymphatic vessel function in aging rescues cerebrospinal fluid drainage","authors":"Ting Du, Aditya Raghunandan, Humberto Mestre, Virginia Plá, Guojun Liu, Antonio Ladrón-de-Guevara, Evan Newbold, Paul Tobin, Daniel Gahn-Martinez, Saurav Pattanayak, Qinwen Huang, Weiguo Peng, Maiken Nedergaard, Douglas H. Kelley","doi":"10.1038/s43587-024-00691-3","DOIUrl":"10.1038/s43587-024-00691-3","url":null,"abstract":"Cervical lymphatic vessels (cLVs) have been shown to drain solutes and cerebrospinal fluid (CSF) from the brain. However, their hydrodynamical properties have never been evaluated in vivo. Here, we developed two-photon optical imaging with particle tracking in vivo of CSF tracers (2P-OPTIC) in superficial and deep cLVs of mice, characterizing their flow and showing that the major driver is intrinsic pumping by contraction of the lymphatic vessel wall. Moreover, contraction frequency and flow velocity were reduced in aged mice, which coincided with a reduction in smooth muscle actin expression. Slowed flow in aged mice was rescued using topical application of prostaglandin F2α, a prostanoid that increases smooth muscle contractility, which restored lymphatic function in aged mice and enhanced central nervous system clearance. We show that cLVs are important regulators of CSF drainage and that restoring their function is an effective therapy for improving clearance in aging. Cervical lymphatics drain cerebrospinal fluid and clear metabolic waste from the brain. Du et al. show using 2P-OPTIC that these are disrupted in aging due to reduced pumping. Restoring cervical lymphatic function with prostaglandin F2α rescues brain clearance.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1418-1431"},"PeriodicalIF":17.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989856","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

Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline 蛋白质组学确定了感染后脑萎缩和认知能力下降的潜在免疫驱动因素。

IF 17

Nature aging Pub Date : 2024-08-14 DOI: 10.1038/s43587-024-00682-4

Michael R. Duggan, Zhongsheng Peng, Pyry N. Sipilä, Joni V. Lindbohm, Jingsha Chen, Yifei Lu, Christos Davatzikos, Guray Erus, Timothy J. Hohman, Shea J. Andrews, Julián Candia, Toshiko Tanaka, Cassandra M. Joynes, Chelsea X. Alvarado, Mike A. Nalls, Jenifer Cordon, Gulzar N. Daya, Yang An, Alexandria Lewis, Abhay Moghekar, Priya Palta, Josef Coresh, Luigi Ferrucci, Mika Kivimäki, Keenan A. Walker

{"title":"Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline","authors":"Michael R. Duggan, Zhongsheng Peng, Pyry N. Sipilä, Joni V. Lindbohm, Jingsha Chen, Yifei Lu, Christos Davatzikos, Guray Erus, Timothy J. Hohman, Shea J. Andrews, Julián Candia, Toshiko Tanaka, Cassandra M. Joynes, Chelsea X. Alvarado, Mike A. Nalls, Jenifer Cordon, Gulzar N. Daya, Yang An, Alexandria Lewis, Abhay Moghekar, Priya Palta, Josef Coresh, Luigi Ferrucci, Mika Kivimäki, Keenan A. Walker","doi":"10.1038/s43587-024-00682-4","DOIUrl":"10.1038/s43587-024-00682-4","url":null,"abstract":"Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe. We identified 260 out of 942 immunologically relevant proteins in plasma that were differentially expressed in individuals with an infection history. Of the infection-related proteins, 35 predicted volumetric changes in brain regions vulnerable to infection-specific atrophy. Several of these proteins, including PIK3CG, PACSIN2, and PRKCB, were related to cognitive decline and plasma biomarkers of dementia (Aβ42/40, GFAP, NfL, pTau-181). Genetic variants that influenced expression of immunologically relevant infection-related proteins, including ITGB6 and TLR5, predicted brain volume loss. Our findings support the role of infections in dementia risk and identify molecular mediators by which infections may contribute to neurodegeneration. This study reveals how infections that increase long-term dementia risk can contribute to longitudinal brain volume loss and regulate immunological proteins in plasma, and which of these proteins may drive infection-specific neurodegeneration.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1263-1278"},"PeriodicalIF":17.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00682-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984264","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

Nonlinear dynamics of multi-omics profiles during human aging 人类衰老过程中多组学特征的非线性动态变化。

IF 17

Nature aging Pub Date : 2024-08-14 DOI: 10.1038/s43587-024-00692-2

Xiaotao Shen, Chuchu Wang, Xin Zhou, Wenyu Zhou, Daniel Hornburg, Si Wu, Michael P. Snyder

{"title":"Nonlinear dynamics of multi-omics profiles during human aging","authors":"Xiaotao Shen, Chuchu Wang, Xin Zhou, Wenyu Zhou, Daniel Hornburg, Si Wu, Michael P. Snyder","doi":"10.1038/s43587-024-00692-2","DOIUrl":"10.1038/s43587-024-00692-2","url":null,"abstract":"Aging is a complex process associated with nearly all diseases. Understanding the molecular changes underlying aging and identifying therapeutic targets for aging-related diseases are crucial for increasing healthspan. Although many studies have explored linear changes during aging, the prevalence of aging-related diseases and mortality risk accelerates after specific time points, indicating the importance of studying nonlinear molecular changes. In this study, we performed comprehensive multi-omics profiling on a longitudinal human cohort of 108 participants, aged between 25 years and 75 years. The participants resided in California, United States, and were tracked for a median period of 1.7 years, with a maximum follow-up duration of 6.8 years. The analysis revealed consistent nonlinear patterns in molecular markers of aging, with substantial dysregulation occurring at two major periods occurring at approximately 44 years and 60 years of chronological age. Distinct molecules and functional pathways associated with these periods were also identified, such as immune regulation and carbohydrate metabolism that shifted during the 60-year transition and cardiovascular disease, lipid and alcohol metabolism changes at the 40-year transition. Overall, this research demonstrates that functions and risks of aging-related diseases change nonlinearly across the human lifespan and provides insights into the molecular and biological pathways involved in these changes. Understanding the molecular changes underlying aging is important for developing biomarkers and healthy aging interventions. In this study, the authors used comprehensive multi-omics data to reveal nonlinear molecular profiles across chronological ages, highlighting two substantial variations observed around ages 40 and 60, which are linked to increased disease risks.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 11","pages":"1619-1634"},"PeriodicalIF":17.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00692-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984263","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

Exploring how APOE ε4 increases Alzheimer’s disease risk in women 探索 APOE ε4 如何增加女性患阿尔茨海默病的风险

IF 17

Nature aging Pub Date : 2024-08-12 DOI: 10.1038/s43587-024-00698-w

George Andrew S. Inglis

引用次数: 0

Real-life intrinsic capacity screening data from the ICOPE-Care program 来自 ICOPE-Care 计划的真实内在能力筛选数据。

IF 17

Nature aging Pub Date : 2024-08-09 DOI: 10.1038/s43587-024-00684-2

Philipe de Souto Barreto, Emmanuel Gonzalez-Bautista, Heike A. Bischoff-Ferrari, Vitor Pelegrim de Oliveira, Renato Gorga Bandeira de Mello, Sandrine Andrieu, Caroline Berbon, Neda Tavassoli, John R. Beard, Yves Rolland, Maria Eugenia Soto Martín, Bruno Vellas

{"title":"Real-life intrinsic capacity screening data from the ICOPE-Care program","authors":"Philipe de Souto Barreto, Emmanuel Gonzalez-Bautista, Heike A. Bischoff-Ferrari, Vitor Pelegrim de Oliveira, Renato Gorga Bandeira de Mello, Sandrine Andrieu, Caroline Berbon, Neda Tavassoli, John R. Beard, Yves Rolland, Maria Eugenia Soto Martín, Bruno Vellas","doi":"10.1038/s43587-024-00684-2","DOIUrl":"10.1038/s43587-024-00684-2","url":null,"abstract":"The Integrated Care for Older People (ICOPE) program is a healthcare pathway that uses a screening test for intrinsic capacity (IC) as its entry point. However, real-life data informing on how IC domains cluster and change over time, as well as their clinical utility, are lacking. Using primary healthcare screening data from more than 20,000 French adults 60 years of age or older, this study identified four clusters of IC impairment: ‘Low impairment’ (most prevalent), ‘Cognition+Locomotion+Hearing+Vision’, ‘All IC impaired’ and ‘Psychology+Vitality+Vision’. Compared to individuals with ‘Low impairment’, those in the other clusters had higher likelihood of having frailty and limitations in both activities of daily living (ADL) and instrumental activities of daily living (IADL), with the strongest associations being observed for ‘All IC impaired’. This study found that ICOPE screening might be a useful tool for patient risk stratification in clinical practice, with a higher number of IC domains impaired at screening indicating a higher probability of functional decline. The Integrated Care for Older People (ICOPE) program was developed to promote a function-centered and individualized approach to healthy aging, but it is not yet widely implemented. In this study, de Souto Barreto et al. used early-stage ICOPE data collected in primary healthcare from more than 20,000 older adults to characterize patterns of intrinsic capacity impairment and associated odds of frailty and disability.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1279-1289"},"PeriodicalIF":17.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914887","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

Decoding the phenotypic mosaic of aging 解码衰老的表型镶嵌。

IF 17

Nature aging Pub Date : 2024-08-09 DOI: 10.1038/s43587-024-00686-0

Liang-Kung Chen

引用次数: 0

Age-associated clonal B cells drive B cell lymphoma in mice 与年龄相关的克隆 B 细胞会诱发小鼠 B 细胞淋巴瘤。

IF 17

Nature aging Pub Date : 2024-08-08 DOI: 10.1038/s43587-024-00671-7

José P. Castro, Anastasia V. Shindyapina, Alessandro Barbieri, Kejun Ying, Olga S. Strelkova, João A. Paulo, Alexander Tyshkovskiy, Rico Meinl, Csaba Kerepesi, Anna P. Petrashen, Marco Mariotti, Margarita V. Meer, Yan Hu, Alexander Karamyshev, Grigoriy Losyev, Mafalda Galhardo, Elsa Logarinho, Artur A. Indzhykulian, Steven P. Gygi, John M. Sedivy, John P. Manis, Vadim N. Gladyshev

{"title":"Age-associated clonal B cells drive B cell lymphoma in mice","authors":"José P. Castro, Anastasia V. Shindyapina, Alessandro Barbieri, Kejun Ying, Olga S. Strelkova, João A. Paulo, Alexander Tyshkovskiy, Rico Meinl, Csaba Kerepesi, Anna P. Petrashen, Marco Mariotti, Margarita V. Meer, Yan Hu, Alexander Karamyshev, Grigoriy Losyev, Mafalda Galhardo, Elsa Logarinho, Artur A. Indzhykulian, Steven P. Gygi, John M. Sedivy, John P. Manis, Vadim N. Gladyshev","doi":"10.1038/s43587-024-00671-7","DOIUrl":"10.1038/s43587-024-00671-7","url":null,"abstract":"Although cancer is an age-related disease, how the processes of aging contribute to cancer progression is not well understood. In this study, we uncovered how mouse B cell lymphoma develops as a consequence of a naturally aged system. We show here that this malignancy is associated with an age-associated clonal B cell (ACBC) population that likely originates from age-associated B cells. Driven by c-Myc activation, promoter hypermethylation and somatic mutations, IgM+ ACBCs clonally expand independently of germinal centers and show increased biological age. ACBCs become self-sufficient and support malignancy when transferred into young recipients. Inhibition of mTOR or c-Myc in old mice attenuates pre-malignant changes in B cells during aging. Although the etiology of mouse and human B cell lymphomas is considered distinct, epigenetic changes in transformed mouse B cells are enriched for changes observed in human B cell lymphomas. Together, our findings characterize the spontaneous progression of cancer during aging through both cell-intrinsic and microenvironmental changes and suggest interventions for its prevention. Castro, Shindyapina et al. explore how aging promotes B cell lymphoma in mice, identifying a population of age-associated clonal B cells that expands through mutation, c-Myc activation and epigenetic alterations to drive age-associated malignancy.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1403-1417"},"PeriodicalIF":17.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908747","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