Nature aging最新文献_第3页

The complex interplay between aging and cancer

IF 17

Nature aging Pub Date : 2025-03-04 DOI: 10.1038/s43587-025-00827-z

Lucrezia A. Trastus, Fabrizio d’Adda di Fagagna

{"title":"The complex interplay between aging and cancer","authors":"Lucrezia A. Trastus, Fabrizio d’Adda di Fagagna","doi":"10.1038/s43587-025-00827-z","DOIUrl":"10.1038/s43587-025-00827-z","url":null,"abstract":"Cancer is an age-related disease, but the interplay between cancer and aging is complex and their shared molecular drivers are deeply intertwined. This Review provides an overview of how different biological pathways affect cancer and aging, leveraging evidence mainly derived from animal studies. We discuss how genome maintenance and accumulation of DNA mutations affect tumorigenesis and tissue homeostasis during aging. We describe how age-related telomere dysfunction and cellular senescence intricately modulate tumor development through mechanisms involving genomic instability and inflammation. We examine how an aged immune system and chronic inflammation shape tumor immunosurveillance, fueling DNA damage and cellular senescence. Finally, as animal models are important to untangling the relative contributions of these aging-modulated pathways to cancer progression and to test interventions, we discuss some of the limitations of physiological and accelerated aging models, aiming to improve experimental designs and enhance translation. This Review explores the intersection between cancer and aging, illustrating shared causal mechanisms including genome instability, telomere dysfunction, cellular senescence and dysregulated immunity and how these can be explored in animal models.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 3","pages":"350-365"},"PeriodicalIF":17.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560428","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

Single-cell transcriptomic atlas of the human testis across the reproductive lifespan.

IF 17

Nature aging Pub 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":"https://doi.org/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":""},"PeriodicalIF":17.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545478","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

What makes biological age epigenetic clocks tick

IF 17

Nature aging Pub Date : 2025-02-24 DOI: 10.1038/s43587-025-00833-1

Mahdi Moqri, Jesse R. Poganik, Steve Horvath, Vadim N. Gladyshev

引用次数: 0

Restoring the primary cilia–autophagy axis in neurons to foster cognitive resilience

IF 17

Nature aging Pub Date : 2025-02-24 DOI: 10.1038/s43587-025-00834-0

引用次数: 0

A primary cilia–autophagy axis in hippocampal neurons is essential to maintain cognitive resilience

IF 17

Nature aging Pub Date : 2025-02-21 DOI: 10.1038/s43587-024-00791-0

Manon Rivagorda, David Romeo-Guitart, Victoria Blanchet, François Mailliet, Valérie Boitez, Natalie Barry, Dimitrije Milunov, Eleni Siopi, Nicolas Goudin, Stéphanie Moriceau, Chiara Guerrera, Michel Leibovici, Soham Saha, Patrice Codogno, Eugenia Morselli, Etienne Morel, Anne-Sophie Armand, Franck Oury

{"title":"A primary cilia–autophagy axis in hippocampal neurons is essential to maintain cognitive resilience","authors":"Manon Rivagorda, David Romeo-Guitart, Victoria Blanchet, François Mailliet, Valérie Boitez, Natalie Barry, Dimitrije Milunov, Eleni Siopi, Nicolas Goudin, Stéphanie Moriceau, Chiara Guerrera, Michel Leibovici, Soham Saha, Patrice Codogno, Eugenia Morselli, Etienne Morel, Anne-Sophie Armand, Franck Oury","doi":"10.1038/s43587-024-00791-0","DOIUrl":"10.1038/s43587-024-00791-0","url":null,"abstract":"Blood-borne factors are essential to maintain neuronal synaptic plasticity and cognitive resilience throughout life. One such factor is osteocalcin (OCN), a hormone produced by osteoblasts that influences multiple physiological processes, including hippocampal neuronal homeostasis. However, the mechanism through which this blood-borne factor communicates with neurons remains unclear. Here we show the importance of a core primary cilium (PC) protein–autophagy axis in mediating the effects of OCN. We found that the OCN receptor GPR158 is present at the PC of hippocampal neurons and mediates the regulation of autophagy machinery by OCN. During aging, autophagy and PC core proteins are reduced in neurons, and restoring their levels is sufficient to improve cognitive impairments in aged mice. Mechanistically, the induction of this axis by OCN is dependent on the PC-dependent cAMP response element-binding protein signaling pathway. Altogether, this study demonstrates that the PC–autophagy axis is a gateway to mediate communication between blood-borne factors and neurons, and it advances understanding of the mechanisms involved in age-related cognitive decline. Exploring the molecular mechanisms by which the blood-borne factor osteocalcin promotes cognitive resilience, Rivagorda, Romeo-Guitart et al. identify a primary cilia axis through which osteocalcin promotes autophagy in neurons.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 3","pages":"450-467"},"PeriodicalIF":17.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00791-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473388","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

Author Correction: Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells. 作者更正：源于龛位的Semaphorin 4A可保护髓系偏异造血干细胞的功能特性。

IF 17

Nature aging Pub Date : 2025-02-20 DOI: 10.1038/s43587-025-00837-x

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

引用次数: 0

Large-scale proteomic analyses of incident Parkinson's disease reveal new pathophysiological insights and potential biomarkers.

IF 17

Nature aging Pub Date : 2025-02-20 DOI: 10.1038/s43587-025-00818-0

Yi-Han Gan, Ling-Zhi Ma, Yi Zhang, Jia You, Yu Guo, Yu He, Lin-Bo Wang, Xiao-Yu He, Yu-Zhu Li, Qiang Dong, Jian-Feng Feng, Wei Cheng, Jin-Tai Yu

{"title":"Large-scale proteomic analyses of incident Parkinson's disease reveal new pathophysiological insights and potential biomarkers.","authors":"Yi-Han Gan, Ling-Zhi Ma, Yi Zhang, Jia You, Yu Guo, Yu He, Lin-Bo Wang, Xiao-Yu He, Yu-Zhu Li, Qiang Dong, Jian-Feng Feng, Wei Cheng, Jin-Tai Yu","doi":"10.1038/s43587-025-00818-0","DOIUrl":"https://doi.org/10.1038/s43587-025-00818-0","url":null,"abstract":"The early pathophysiology of Parkinson's disease (PD) is poorly understood. We analyzed 2,920 Olink-measured plasma proteins in 51,804 UK Biobank participants, identifying 859 incident PD cases after 14.45 years. We found 38 PD-related proteins, with six of the top ten validated in the Parkinson's Progression Markers Initiative (PPMI) cohort. ITGAV, HNMT and ITGAM showed consistent significant association (hazard ratio: 0.11-0.57, P = 6.90 × 10-24 to 2.10 × 10-11). Lipid metabolism dysfunction was evident 15 years before PD onset, and levels of BAG3, HPGDS, ITGAV and PEPD continuously decreased before diagnosis. These proteins were linked to prodromal symptoms and brain measures. Mendelian randomization suggested ITGAM and EGFR as potential causes of PD. A predictive model using machine learning combined the top 16 proteins and demographics, achieving high accuracy for 5-year (area under the curve (AUC) = 0.887) and over-5-year PD prediction (AUC = 0.816), outperforming demographic-only models. It was externally validated in PPMI (AUC = 0.802). Our findings reveal early peripheral pathophysiological changes in PD crucial for developing early biomarkers and precision therapies.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470356","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

FGF21 keeps the thymus young.

IF 17

Nature aging Pub Date : 2025-02-19 DOI: 10.1038/s43587-025-00814-4

Yousuke Takahama

引用次数: 0

Paracrine FGF21 dynamically modulates mTOR signaling to regulate thymus function across the lifespan.

IF 17

Nature aging Pub 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":""},"PeriodicalIF":17.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460848","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

Enhanced paracrine action of FGF21 in stromal cells delays thymic aging.

IF 17

Nature aging Pub Date : 2025-02-19 DOI: 10.1038/s43587-025-00813-5

Yun-Hee Youm, Christy Gliniak, Yuan Zhang, Tamara Dlugos, Philipp E Scherer, Vishwa Deep Dixit

引用次数: 0