Nature aging最新文献_第9页

Mitochondria-enriched hematopoietic stem cells exhibit elevated self-renewal capabilities, thriving within the context of aged bone marrow. 富含线粒体的造血干细胞表现出更高的自我更新能力，在衰老的骨髓中茁壮成长。

IF 17

Nature aging Pub Date : 2025-05-01 Epub Date: 2025-03-06 DOI: 10.1038/s43587-025-00828-y

Haruhito Totani, Takayoshi Matsumura, Rui Yokomori, Terumasa Umemoto, Yuji Takihara, Chong Yang, Lee Hui Chua, Atsushi Watanabe, Takaomi Sanda, Toshio Suda

引用次数: 0

Interplay of somatic mutations and epigenetic aging clocks. 体细胞突变与表观遗传衰老时钟的相互作用。

IF 17

Nature aging Pub Date : 2025-04-01 DOI: 10.1038/s43587-025-00846-w

Wolfgang Wagner

引用次数: 0

Somatic mutation as an explanation for epigenetic aging. 体细胞突变是表观遗传衰老的一种解释。

IF 17

Nature aging Pub Date : 2025-04-01 Epub Date: 2025-01-13 DOI: 10.1038/s43587-024-00794-x

Zane Koch, Adam Li, Daniel S Evans, Steven Cummings, Trey Ideker

引用次数: 0

FGF21 keeps the thymus young. FGF21使胸腺保持年轻。

IF 17

Nature aging Pub Date : 2025-04-01 DOI: 10.1038/s43587-025-00814-4

Yousuke Takahama

引用次数: 0

Alarmingly large care deficits globally for people living with dementia and disability. 全球对痴呆症和残疾患者的护理缺口惊人。

IF 17

Nature aging Pub Date : 2025-04-01 DOI: 10.1038/s43587-025-00849-7

引用次数: 0

Paracrine FGF21 dynamically modulates mTOR signaling to regulate thymus function across the lifespan. 旁分泌FGF21动态调节mTOR信号，调节胸腺功能。

IF 17

Nature aging Pub Date : 2025-04-01 Epub Date: 2025-02-19 DOI: 10.1038/s43587-024-00801-1

Sarah A Wedemeyer, Nicholas E Jones, Iwan G A Raza, Freedom M Green, Yangming Xiao, Manpreet K Semwal, Aaron K Garza, Kahealani S Archuleta, Kymberly L Wimberly, Thomas Venables, Georg A Holländer, Ann V Griffith

{"title":"Paracrine FGF21 dynamically modulates mTOR signaling to regulate thymus function across the lifespan.","authors":"Sarah A Wedemeyer, Nicholas E Jones, Iwan G A Raza, Freedom M Green, Yangming Xiao, Manpreet K Semwal, Aaron K Garza, Kahealani S Archuleta, Kymberly L Wimberly, Thomas Venables, Georg A Holländer, Ann V Griffith","doi":"10.1038/s43587-024-00801-1","DOIUrl":"10.1038/s43587-024-00801-1","url":null,"abstract":"Consequences of age-associated thymic atrophy include declining T-cell responsiveness to pathogens and vaccines and diminished T-cell self-tolerance. Cortical thymic epithelial cells (cTECs) are primary targets of thymic aging, and recent studies suggested that their maintenance requires mTOR signaling downstream of medullary TEC (mTEC)-derived growth factors. Here, to test this hypothesis, we generated a knock-in mouse model in which FGF21 and mCherry are expressed by most mTECs. We find that mTEC-derived FGF21 promotes temporally distinct patterns of mTORC1 and mTORC2 signaling in cTECs, promotes thymus and individual cTEC growth and maintenance, increases T-cell responsiveness to viral infection, and diminishes indicators of peripheral autoimmunity in older mice. The effects of FGF21 overexpression on thymus size and mTOR signaling were abrogated by treatment with the mTOR inhibitor rapamycin. These results reveal a mechanism by which paracrine FGF21 signaling regulates thymus size and function throughout the lifespan, as well as potential therapeutic targets for improving T-cell function and tolerance in aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"588-606"},"PeriodicalIF":17.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460848","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

Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells. 小生境衍生的信号蛋白4A保护骨髓偏向性造血干细胞的功能特性。

IF 17

Nature aging Pub Date : 2025-04-01 Epub Date: 2025-01-29 DOI: 10.1038/s43587-024-00798-7

Dorsa Toghani, Sanika Gupte, Sharon Zeng, Elmir Mahammadov, Edie I Crosse, Negar Seyedhassantehrani, Christian Burns, David Gravano, Stefan Radtke, Hans-Peter Kiem, Sonia Rodriguez, Nadia Carlesso, Amogh Pradeep, Alexis Georgiades, Fabienne Lucas, Nicola K Wilson, Sarah J Kinston, Berthold Göttgens, Le Zong, Isabel Beerman, Bongsoo Park, Derek H Janssens, Daniel Jones, Ali Toghani, Claus Nerlov, Eric M Pietras, Marion Mesnieres, Christa Maes, Atsushi Kumanogoh, Thomas Worzfeld, Jin-Gyu Cheong, Steven Z Josefowicz, Peter Kharchenko, David T Scadden, Antonio Scialdone, Joel A Spencer, Lev Silberstein

{"title":"Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.","authors":"Dorsa Toghani, Sanika Gupte, Sharon Zeng, Elmir Mahammadov, Edie I Crosse, Negar Seyedhassantehrani, Christian Burns, David Gravano, Stefan Radtke, Hans-Peter Kiem, Sonia Rodriguez, Nadia Carlesso, Amogh Pradeep, Alexis Georgiades, Fabienne Lucas, Nicola K Wilson, Sarah J Kinston, Berthold Göttgens, Le Zong, Isabel Beerman, Bongsoo Park, Derek H Janssens, Daniel Jones, Ali Toghani, Claus Nerlov, Eric M Pietras, Marion Mesnieres, Christa Maes, Atsushi Kumanogoh, Thomas Worzfeld, Jin-Gyu Cheong, Steven Z Josefowicz, Peter Kharchenko, David T Scadden, Antonio Scialdone, Joel A Spencer, Lev Silberstein","doi":"10.1038/s43587-024-00798-7","DOIUrl":"10.1038/s43587-024-00798-7","url":null,"abstract":"Somatic stem cell pools comprise diverse, highly specialized subsets whose individual contribution is critical for the overall regenerative function. In the bone marrow, myeloid-biased hematopoietic stem cells (myHSCs) are indispensable for replenishment of myeloid cells and platelets during inflammatory response but, at the same time, become irreversibly damaged during inflammation and aging. Here we identify an extrinsic factor, Semaphorin 4A (Sema4A), which non-cell-autonomously confers myHSC resilience to inflammatory stress. We show that, in the absence of Sema4A, myHSC inflammatory hyper-responsiveness in young mice drives excessive myHSC expansion, myeloid bias and profound loss of regenerative function with age. Mechanistically, Sema4A is mainly produced by neutrophils, signals via a cell surface receptor, Plexin D1, and safeguards the myHSC epigenetic state. Our study shows that, by selectively protecting a distinct stem cell subset, an extrinsic factor preserves functional diversity of somatic stem cell pool throughout organismal lifespan.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"558-575"},"PeriodicalIF":17.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12025894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070472","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

Interleukin-12 signaling drives Alzheimer's disease pathology through disrupting neuronal and oligodendrocyte homeostasis. 白细胞介素-12信号通过破坏神经元和少突胶质细胞的稳态来驱动阿尔茨海默病的病理。

IF 17

Nature aging Pub Date : 2025-04-01 Epub Date: 2025-03-13 DOI: 10.1038/s43587-025-00816-2

Shirin Schneeberger, Seung Joon Kim, Maria N Geesdorf, Ekaterina Friebel, Pascale Eede, Marina Jendrach, Anastasiya Boltengagen, Caroline Braeuning, Torben Ruhwedel, Andreas J Hülsmeier, Niclas Gimber, Marlene Foerster, Juliane Obst, Myrto Andreadou, Sarah Mundt, Jan Schmoranzer, Stefan Prokop, Wiebke Kessler, Tanja Kuhlmann, Wiebke Möbius, Klaus-Armin Nave, Thorsten Hornemann, Burkhard Becher, Julia M Edgar, Nikos Karaiskos, Christine Kocks, Nikolaus Rajewsky, Frank L Heppner

{"title":"Interleukin-12 signaling drives Alzheimer's disease pathology through disrupting neuronal and oligodendrocyte homeostasis.","authors":"Shirin Schneeberger, Seung Joon Kim, Maria N Geesdorf, Ekaterina Friebel, Pascale Eede, Marina Jendrach, Anastasiya Boltengagen, Caroline Braeuning, Torben Ruhwedel, Andreas J Hülsmeier, Niclas Gimber, Marlene Foerster, Juliane Obst, Myrto Andreadou, Sarah Mundt, Jan Schmoranzer, Stefan Prokop, Wiebke Kessler, Tanja Kuhlmann, Wiebke Möbius, Klaus-Armin Nave, Thorsten Hornemann, Burkhard Becher, Julia M Edgar, Nikos Karaiskos, Christine Kocks, Nikolaus Rajewsky, Frank L Heppner","doi":"10.1038/s43587-025-00816-2","DOIUrl":"10.1038/s43587-025-00816-2","url":null,"abstract":"Neuroinflammation including interleukin (IL)-12/IL-23-signaling is central to Alzheimer's disease (AD) pathology. Inhibition of p40, a subunit of IL-12/IL-23, attenuates pathology in AD-like mice; however, its signaling mechanism and expression pattern remained elusive. Here we show that IL-12 receptors are predominantly expressed in neurons and oligodendrocytes in AD-like APPPS1 mice and in patients with AD, whereas IL-23 receptor transcripts are barely detectable. Consistently, deletion of the IL-12 receptor in neuroectodermal cells ameliorated AD pathology in APPPS1 mice, whereas removal of IL-23 receptors had no effect. Genetic ablation of IL-12 signaling alone reverted the loss of mature oligodendrocytes, restored myelin homeostasis, rescued the amyloid-β-dependent reduction of parvalbumin-positive interneurons and restored phagocytosis-related changes in microglia of APPPS1 mice. Furthermore, IL-12 protein expression was increased in human AD brains compared to healthy age-matched controls, and human oligodendrocyte-like cells responded profoundly to IL-12 stimulation. We conclude that oligodendroglial and neuronal IL-12 signaling, but not IL-23 signaling, are key in orchestrating AD-related neuroimmune crosstalk and that IL-12 represents an attractive therapeutic target in AD.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"622-641"},"PeriodicalIF":17.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627337","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

Single-cell transcriptomic atlas of the human testis across the reproductive lifespan. 人类生殖期睾丸单细胞转录组图谱。

IF 17

Nature aging Pub Date : 2025-04-01 Epub Date: 2025-03-03 DOI: 10.1038/s43587-025-00824-2

Lina Cui, Xichen Nie, Yixuan Guo, Pengcheng Ren, Yifei Guo, Xiaoyan Wang, Ran Li, James M Hotaling, Bradley R Cairns, Jingtao Guo

{"title":"Single-cell transcriptomic atlas of the human testis across the reproductive lifespan.","authors":"Lina Cui, Xichen Nie, Yixuan Guo, Pengcheng Ren, Yifei Guo, Xiaoyan Wang, Ran Li, James M Hotaling, Bradley R Cairns, Jingtao Guo","doi":"10.1038/s43587-025-00824-2","DOIUrl":"10.1038/s43587-025-00824-2","url":null,"abstract":"Testicular aging is associated with declining reproductive health, but the molecular mechanisms are unclear. Here we generate a dataset of 214,369 single-cell transcriptomes from testicular cells of 35 individuals aged 21-69, offering a resource for studying testicular aging and physiology. Machine learning analysis reveals a stronger aging response in somatic cells compared to germ cells. Two waves of aging-related changes are identified: the first in peritubular cells of donors in their 30s, marked by increased basement membrane thickness, indicating a priming state for aging. In their 50s, testicular cells exhibit functional changes, including altered steroid metabolism in Leydig cells and immune responses in macrophages. Further analyses reveal the impact of body mass index on spermatogenic capacity as age progresses, particularly after age 45. Altogether, our findings illuminate molecular alterations during testis aging and their relationship with body mass index, providing a foundation for future research and offering potential diagnostic markers and therapeutic targets.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"658-674"},"PeriodicalIF":17.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545478","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

Absence of care among community-dwelling older adults with dementia and functional limitations. 社区居住的老年痴呆患者和功能限制患者缺乏护理。

IF 17

Nature aging Pub Date : 2025-04-01 Epub Date: 2025-03-17 DOI: 10.1038/s43587-025-00836-y

Zhuoer Lin, Yuting Qian, Thomas M Gill, Xiaohui Hou, Heather Allore, Shanquan Chen, Xi Chen

{"title":"Absence of care among community-dwelling older adults with dementia and functional limitations.","authors":"Zhuoer Lin, Yuting Qian, Thomas M Gill, Xiaohui Hou, Heather Allore, Shanquan Chen, Xi Chen","doi":"10.1038/s43587-025-00836-y","DOIUrl":"10.1038/s43587-025-00836-y","url":null,"abstract":"Assistance with daily activities is crucial for persons living with dementia and functional limitations, yet many face substantial challenges in accessing adequate care and support. Using harmonized longitudinal survey data (2012-2018) from the United States, England, 18 European countries, Israel and China, we found that at least one-fifth of persons with dementia and functional limitations received no personal assistance for basic activities of daily living or instrumental activities of daily living, regardless of regional development level. Care gaps were widespread across both basic activities of daily living or instrumental activities of daily living limitations, as well as for informal and formal care. Disparities were evident, with less educated people more likely to lack formal care, whereas those living alone often lacked informal support, resulting in the absence of any care. Alarmingly, care availability showed no improvement over time. Our findings underscore the urgent need for policies to address inequities and ensure critical access to care services for this vulnerable population worldwide.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"548-557"},"PeriodicalIF":17.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652908","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