Nature aging最新文献

{"title":"A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging","authors":"Charlène Iltis, Iryna Moskalevska, Antoine Debiesse, Laetitia Seguin, Christina Fissoun, Ludovic Cervera, Lyvia Moudombi, Maude Ardin, Anthony Ferrari, Coline Eliott, Didier Pisani, Alexandre Ottaviani, Manon Bourinet, Carmelo Luci, Philippe Gual, Gabriela Makulyte, David Bernard, Manon Durandy, Lou C. Duret, Tynhinane Hamidouche, Sarah Kunz, Olivier Croce, Clément Delannoy, Yann Guérardel, Fabrice Allain, Paul Hofman, Delphine Benarroch-Popivker, Laurence Bianchini, Berengère Dadone-Montaudie, Estelle Cosson, Julien Guglielmi, Thierry Pourcher, Véronique M. Braud, Marina Shkreli, Yves-Marie Pers, Christian Jorgensen, Jean-Marc Brondello, Chloé C. Féral, Marie-Cécile Michallet, Eric Gilson, Julien Cherfils-Vicini","doi":"10.1038/s43587-024-00776-z","DOIUrl":"10.1038/s43587-024-00776-z","url":null,"abstract":"Although senescent cells can be eliminated by the immune system, they tend to accumulate with age in various tissues. Here we show that senescent cells can evade immune clearance by natural killer (NK) cells by upregulating the expression of the disialylated ganglioside GD3 at their surface. The increased level of GD3 expression on senescent cells that naturally occurs upon aging in liver, lung, kidney or bones leads to a strong suppression of NK-cell-mediated immunosurveillance. In mice, we found that targeting GD3+ senescent cells with anti-GD3 immunotherapy attenuated the development of experimentally induced or age-related lung and liver fibrosis and age-related bone remodeling. These results demonstrate that GD3 upregulation confers immune privilege to senescent cells. We propose that GD3 acts as a senescence immune checkpoint (SIC) that allows senescent cells to escape immunosurveillance and to trigger immune anergy during aging. This study identifies a novel immune checkpoint in senescent cells that is linked to the ganglioside GD3 and that contributes to the evasion of immune clearance by these cells and to aging and age-related diseases.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 2","pages":"219-236"},"PeriodicalIF":17.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00776-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900706","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":"Generation of a selective senolytic platform using a micelle-encapsulated Sudan Black B conjugated analog","authors":"Sophia Magkouta, Dimitris Veroutis, Angelos Papaspyropoulos, Maria Georgiou, Nikolaos Lougiakis, Natassa Pippa, Sophia Havaki, Anastasia Palaiologou, Dimitris-Foivos Thanos, Konstantinos Kambas, Nefeli Lagopati, Nikos Boukos, Nicole Pouli, Panagiotis Marakos, Athanassios Kotsinas, Dimitris Thanos, Konstantinos Evangelou, Fotios Sampaziotis, Constantin Tamvakopoulos, Stergios Pispas, Russell Petty, Nicholas Kotopoulos, Vassilis G. Gorgoulis","doi":"10.1038/s43587-024-00747-4","DOIUrl":"10.1038/s43587-024-00747-4","url":null,"abstract":"The emerging field of senolytics is centered on eliminating senescent cells to block their contribution to the progression of age-related diseases, including cancer, and to facilitate healthy aging. Enhancing the selectivity of senolytic treatments toward senescent cells stands to reduce the adverse effects associated with existing senolytic interventions. Taking advantage of lipofuscin accumulation in senescent cells, we describe here the development of a highly efficient senolytic platform consisting of a lipofuscin-binding domain scaffold, which can be conjugated with a senolytic drug via an ester bond. As a proof of concept, we present the generation of GL392, a senolytic compound that carries a dasatinib senolytic moiety. Encapsulation of the GL392 compound in a micelle nanocarrier (termed mGL392) allows for both in vitro and in vivo (in mice) selective elimination of senescent cells via targeted release of the senolytic agent with minimal systemic toxicity. Our findings suggest that this platform could be used to enhance targeting of senotherapeutics toward senescent cells. Exploiting the selective accumulation of lipofuscin in senescent cells, the authors developed a targeted senolytic platform. As proof of concept, they show that selective delivery of dasatinib elicits senolysis with minimal toxicity, in vitro, in organoids and in mice.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 1","pages":"162-175"},"PeriodicalIF":17.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00747-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900713","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":"Structural inequality linked to brain volume and network dynamics in aging and dementia across the Americas","authors":"Agustina Legaz, Florencia Altschuler, Raul Gonzalez-Gomez, Hernán Hernández, Sandra Baez, Joaquín Migeot, Sol Fittipaldi, Vicente Medel, Marcelo Adrián Maito, María E. Godoy, Sebastián Moguilner, Josephine Cruzat, Carlos Coronel-Oliveros, Enzo Tagliazuchi, Hernando Santamaria Garcia, Francesca R. Farina, Pablo Reyes, Shireen Javandel, Adolfo M. García, Álvaro Deleglise, Diana L. Matallana, José Alberto Avila-Funes, Andrea Slachevsky, María I. Behrens, Nilton Custodio, Catalina Trujillo-Llano, Juan F. Cardona, Pablo Barttfeld, Ignacio L. Brusco, Martín A. Bruno, Ana L. Sosa Ortiz, Stefanie D. Pina-Escudero, Leonel T. Takada, Elisa de Paula França Resende, Katherine L. Possin, Maira Okada de Oliveira, Kun Hu, Francisco Lopera, Brian Lawlor, Victor Valcour, Jennifer S. Yokoyama, Bruce Miller, Agustin Ibañez","doi":"10.1038/s43587-024-00781-2","DOIUrl":"10.1038/s43587-024-00781-2","url":null,"abstract":"Structural inequality, the uneven distribution of resources and opportunities, influences health outcomes. However, the biological embedding of structural inequality in aging and dementia, especially among underrepresented populations, is unclear. We examined the association between structural inequality (country-level and state-level Gini indices) and brain volume and connectivity in 2,135 healthy controls, and individuals with Alzheimer’s disease and frontotemporal lobe degeneration from Latin America and the United States. Greater structural inequality was linked to reduced brain volume and connectivity, with stronger effects in Latin America, especially in the temporo-cerebellar, fronto-thalamic and hippocampal regions. In the United States, milder effects were observed in the insular-cingular and temporal areas. Results were more pronounced in Alzheimer’s disease and were independent of age, sex, education, cognition and other confounding factors. The findings highlight the critical role of structural inequality in aging and dementia, emphasizing the biological embedding of macrosocial factors and the need for targeted interventions in underserved populations. The authors find that structural economic inequality is linked to reduced brain volume and connectivity in middle-aged and older adults across the Americas, more so in Alzheimer’s disease than in frontotemporal dementia. The findings emphasize the biological embedding of inequality in aging and dementia.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 2","pages":"259-274"},"PeriodicalIF":17.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900914","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":"A global analysis of adaptation to societal aging across low-, middle- and high-income countries using the Global Aging Society Index","authors":"Cynthia Chen, Julian Lim, Jemima Koh, John Beard, John W. Rowe, for the Research Network on an Aging Society","doi":"10.1038/s43587-024-00772-3","DOIUrl":"10.1038/s43587-024-00772-3","url":null,"abstract":"We have previously presented a multidimensional Aging Society Index, a weighted summation of five domains central to successful adaptation to societal aging: well-being, productivity and engagement, equity, cohesion and security, as a tool to assess countries’ adaptation to demographic transformation. As the index was based on data from developed countries and some of the individual metrics or weightings may not be well suited for application to low- and middle-income countries, we here present the scores on a modified index (Global Aging Society Index) on 143 countries distributed across the span of economic development. Only 5 out of 143 (3.5%) countries had higher scores for women than men. Countries with the most notable gender differences were primarily low-income countries. The multidimensional index permits cross-national comparisons and may facilitate the identification of targets for developing policies and programs to enhance the likelihood that older persons will age successfully. The authors score and rank the adaptation to societal aging across 143 countries using a newly developed index called the Global Aging Society Index, which may be helpful to identify targets for the development of policies and programs to enhance the likelihood that older people will age successfully.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 1","pages":"113-121"},"PeriodicalIF":17.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00772-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900708","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":"Cohort trends in intrinsic capacity in England and China","authors":"John R. Beard, Katja Hanewald, Yafei Si, Jotheeswaran Amuthavalli Thiyagarajan, Dario Moreno-Agostino","doi":"10.1038/s43587-024-00741-w","DOIUrl":"10.1038/s43587-024-00741-w","url":null,"abstract":"To understand how the health of older adults today compares to that of previous generations, we estimated intrinsic capacity and subdomains of cognitive, locomotor, sensory, psychological and vitality capacities in participants of the English Longitudinal Study of Ageing and the China Health and Retirement Longitudinal Study. Applying multilevel growth curve models, we found that more recent cohorts entered older ages with higher levels of capacity, while subsequent age-related declines were somewhat compressed compared to earlier cohorts. Trends were most evident for the cognitive, locomotor and vitality capacities. Improvements were large, with the greatest gains being in the most recent cohorts. For example, a 68-year-old participant of the English Longitudinal Study of Ageing born in 1950 had higher capacity than a 62-year-old born 10 years earlier. Trends were similar for men and women and were generally consistent across English and Chinese cohorts. Possible causes include broad societal influences and improvements in medical care. Intrinsic capacity includes a person’s mental and physical capacities. The authors examined cohort trends in intrinsic capacity in two large English and Chinese studies. They report that more recently born participants entered older ages with markedly higher levels of functioning, while subsequent age-related declines were somewhat delayed.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 1","pages":"87-98"},"PeriodicalIF":17.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00741-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866850","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":"Supporting the sexual healthcare needs of aging women","authors":"Holly N. Thomas","doi":"10.1038/s43587-024-00725-w","DOIUrl":"10.1038/s43587-024-00725-w","url":null,"abstract":"A satisfying sex life is a key component of health and well-being for many older women. However, there is insufficient awareness of and care for women’s sexual health. This Comment discusses steps healthcare providers can take to support women’s sexual health across the lifespan, which should be a top priority.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 12","pages":"1660-1662"},"PeriodicalIF":17.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821506","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":"Emerging therapeutic strategies to mitigate female and male reproductive aging","authors":"Yasmyn E. Winstanley, Jennifer S. Stables, Macarena B. Gonzalez, Takashi Umehara, Robert J. Norman, Rebecca L. Robker","doi":"10.1038/s43587-024-00771-4","DOIUrl":"10.1038/s43587-024-00771-4","url":null,"abstract":"People today are choosing to have children later in life, often in their thirties and forties, when their fertility is in decline. We sought to identify and compile effective methods for improving either male or female fertility in this context of advanced reproductive age. We found few clinical studies with strong evidence for therapeutics that mitigate reproductive aging or extend fertility; however, this Perspective summarizes the range of emerging experimental strategies under development. Preclinical studies, in mouse models of aging, have identified pharmaceutical candidates that improve egg and sperm quality. Further, a diverse array of medically assisted reproduction methodologies, including those that stimulate rare ovarian follicles and rejuvenate egg quality using mitochondria, may have future utility for older patients. Finally, we highlight the many knowledge gaps and possible future directions in the field of therapeutics to extend the age of healthy human reproduction. People now choose to start families in their 30s to 40s, when fertility is low owing to reproductive aging. In this Perspective, the authors highlight the absence of clinically confirmed therapeutics to mitigate reproductive aging or extend fertility, and they summarize the range of emerging strategies and point to knowledge gaps and future directions in the field.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 12","pages":"1682-1696"},"PeriodicalIF":17.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821520","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":"Healthy longevity requires bridging reproductive medicine, aging research and public engagement","authors":"Zhongwei Huang, on behalf of NUS Bia-Echo Asia Centre for Reproductive Longevity and Equality (ACRLE)","doi":"10.1038/s43587-024-00713-0","DOIUrl":"10.1038/s43587-024-00713-0","url":null,"abstract":"Reproductive health is fundamentally connected with overall health. The Bia-Echo Asia Centre for Reproductive Longevity and Equality discusses an innovative approach to healthy longevity that is tailored uniquely to individual patterns of aging, which will require reproductive medicine, biological aging research and public engagement to join forces.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 12","pages":"1658-1659"},"PeriodicalIF":17.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821519","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":"Healthy aging in individuals born after assisted reproductive technology is a research area for the future","authors":"Anna Sophie Lebech Kjaer, Maria Linander Vestager, Rikke Beck Jensen, Anja Pinborg","doi":"10.1038/s43587-024-00721-0","DOIUrl":"10.1038/s43587-024-00721-0","url":null,"abstract":"As fertility rates decline and childbearing age increases globally, assisted reproductive technology (ART) has a crucial role in enhancing birth rates and will contribute substantially to future generations. ART has fulfilled family formation wishes for many individuals facing infertility and aids in solving demographic challenges. Today, up to 9% of the European population is conceived after ART. Considerable advancements in ARTs have improved the effectiveness of treatment, but the ultimate quality control in ART is healthy offspring. Therefore, it is of utmost importance to monitor the health of individuals conceived through ART, and ensure that ART not only provides for the birth of healthy children but also for health into old age.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 12","pages":"1663-1666"},"PeriodicalIF":17.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821511","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":"Reproductive aging research as a gateway to health and wellbeing","authors":"","doi":"10.1038/s43587-024-00786-x","DOIUrl":"10.1038/s43587-024-00786-x","url":null,"abstract":"Reproductive aging is increasingly recognized as an important determinant of fertility span and overall health and wellbeing in older age. In this Focus issue, Nature Aging presents a series of reviews and opinion pieces on recent advances in reproductive aging research.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 12","pages":"1657-1657"},"PeriodicalIF":17.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00786-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821513","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}