Nature aging最新文献_第2页

Modulating mTOR-dependent astrocyte substate transitions to alleviate neurodegeneration. 调节mtor依赖性星形胶质细胞亚状态转变以减轻神经退行性变。

IF 17

Nature aging Pub Date : 2025-01-08 DOI: 10.1038/s43587-024-00792-z

Liansheng Zhang, Zhengzheng Xu, Zhiheng Jia, Shicheng Cai, Qiang Wu, Xingyu Liu, Xinde Hu, Tao Bai, Yongyu Chen, Tianwen Li, Zhen Liu, Bin Wu, Jianhong Zhu, Haibo Zhou

{"title":"Modulating mTOR-dependent astrocyte substate transitions to alleviate neurodegeneration.","authors":"Liansheng Zhang, Zhengzheng Xu, Zhiheng Jia, Shicheng Cai, Qiang Wu, Xingyu Liu, Xinde Hu, Tao Bai, Yongyu Chen, Tianwen Li, Zhen Liu, Bin Wu, Jianhong Zhu, Haibo Zhou","doi":"10.1038/s43587-024-00792-z","DOIUrl":"https://doi.org/10.1038/s43587-024-00792-z","url":null,"abstract":"Traditional approaches to studying astrocyte heterogeneity have mostly focused on analyzing static properties, failing to identify whether subtypes represent intermediate or final states of reactive astrocytes. Here we show that previously proposed neuroprotective and neurotoxic astrocytes are transitional states rather than distinct subtypes, as revealed through time-series multiomic sequencing. Neuroprotective astrocytes are an intermediate state of the transition from a nonreactive to a neurotoxic state in response to neuroinflammation, a process regulated by the mTOR signaling pathway. In Alzheimer's disease (AD) and aging, we observed an imbalance in neurotoxic and neuroprotective astrocytes in animal models and human patients. Moreover, targeting mTOR in astrocytes with rapamycin or shRNA mitigated astrocyte neurotoxic effects in neurodegenerative mouse models. Overall, our study uncovers a mechanism through which astrocytes exhibit neuroprotective functions before becoming neurotoxic under neuroinflammatory conditions and highlights mTOR modulation specifically in astrocytes as a potential therapeutic strategy for neurodegenerative diseases.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960792","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

The evolution of geriatric day hospitals in Ireland 爱尔兰老年病日间医院的演变。

IF 17

Nature aging Pub Date : 2025-01-03 DOI: 10.1038/s43587-024-00789-8

Román Romero-Ortuño

引用次数: 0

Plasma proteins associated with the brain age gap 血浆蛋白与大脑年龄差距有关。

IF 17

Nature aging Pub Date : 2025-01-03 DOI: 10.1038/s43587-024-00780-3

Erik C. B. Johnson

引用次数: 0

Seventy really may be the new sixty for English baby boomers 对于英国婴儿潮一代来说，70岁真的可能是新的60岁。

IF 17

Nature aging Pub Date : 2025-01-03 DOI: 10.1038/s43587-024-00796-9

引用次数: 0

Balancing the promise and risks of geroscience interventions 平衡地球科学干预措施的前景与风险。

IF 17

Nature aging Pub Date : 2025-01-03 DOI: 10.1038/s43587-024-00788-9

Alan A. Cohen, John R. Beard, Luigi Ferrucci, Tamàs Fülöp, Vadim N. Gladyshev, Mahdi Moqri, Marcel G. M. Olde Rikkert, Martin Picard

引用次数: 0

Author Correction: Genetics of female and male reproductive traits and their relationship with health, longevity and consequences for offspring. 作者更正：女性和男性生殖特征的遗传学及其与健康、寿命和后代后果的关系。

IF 17

Nature aging Pub Date : 2025-01-02 DOI: 10.1038/s43587-024-00800-2

Stefania Benonisdottir, Vincent J Straub, Augustine Kong, Melinda C Mills

引用次数: 0

Chronic stress induces senescence build-up early in life 慢性压力会在生命早期引起衰老。

IF 17

Nature aging Pub Date : 2025-01-02 DOI: 10.1038/s43587-024-00774-1

Victor Lau, Ifeoluwa Awogbindin, Marie-Ève Tremblay

引用次数: 0

Restoring aging-related tissue homeostasis via reactivated innate immunotherapy 通过再激活先天免疫疗法恢复衰老相关组织的稳态。

IF 17

Nature aging Pub Date : 2025-01-02 DOI: 10.1038/s43587-024-00782-1

引用次数: 0

A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging. 基于神经节苷脂的免疫检查点使衰老细胞在衰老过程中逃避免疫监视。

IF 17

Nature aging Pub Date : 2024-12-27 DOI: 10.1038/s43587-024-00776-z

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

{"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.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900706","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

Generation of a selective senolytic platform using a micelle-encapsulated Sudan Black B conjugated analog 利用胶束包裹的苏丹黑 B 共轭类似物生成选择性衰老分解平台。

IF 17

Nature aging Pub Date : 2024-12-27 DOI: 10.1038/s43587-024-00747-4

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

{"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}

引用次数: 0