Nature aging最新文献_第2页

Interleukin-12 signaling drives Alzheimer's disease pathology through disrupting neuronal and oligodendrocyte homeostasis.

IF 17

Nature aging Pub 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":""},"PeriodicalIF":17.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627337","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 Women In Autophagy network empowers global equity in science.

IF 17

Nature aging Pub Date : 2025-03-12 DOI: 10.1038/s43587-025-00839-9

Ghita Ghislat, Inmaculada Tasset

引用次数: 0

Palliative care use in Taiwanese older adults

IF 17

Nature aging Pub Date : 2025-03-11 DOI: 10.1038/s43587-025-00843-z

Anna Kriebs

引用次数: 0

Exposing the exposome in aging

IF 17

Nature aging Pub Date : 2025-03-11 DOI: 10.1038/s43587-025-00845-x

George Andrew S. Inglis

引用次数: 0

Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease

IF 17

Nature aging Pub Date : 2025-03-10 DOI: 10.1038/s43587-025-00823-3

Yifei Cai, Jean Kanyo, Rashaun Wilson, Shveta Bathla, Pablo Leal Cardozo, Lei Tong, Shanshan Qin, Lukas A. Fuentes, Iguaracy Pinheiro-de-Sousa, Tram Huynh, Liyuan Sun, Mohammad Shahid Mansuri, Zichen Tian, Hao-Ran Gan, Amber Braker, Hoang Kim Trinh, Anita Huttner, TuKiet T. Lam, Evangelia Petsalaki, Kristen J. Brennand, Angus C. Nairn, Jaime Grutzendler

{"title":"Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease","authors":"Yifei Cai, Jean Kanyo, Rashaun Wilson, Shveta Bathla, Pablo Leal Cardozo, Lei Tong, Shanshan Qin, Lukas A. Fuentes, Iguaracy Pinheiro-de-Sousa, Tram Huynh, Liyuan Sun, Mohammad Shahid Mansuri, Zichen Tian, Hao-Ran Gan, Amber Braker, Hoang Kim Trinh, Anita Huttner, TuKiet T. Lam, Evangelia Petsalaki, Kristen J. Brennand, Angus C. Nairn, Jaime Grutzendler","doi":"10.1038/s43587-025-00823-3","DOIUrl":"10.1038/s43587-025-00823-3","url":null,"abstract":"Dystrophic neurites (also termed axonal spheroids) are found around amyloid deposits in Alzheimer’s disease (AD), where they impair axonal electrical conduction, disrupt neural circuits and correlate with AD severity. Despite their importance, the mechanisms underlying spheroid formation remain incompletely understood. To address this, we developed a proximity labeling approach to uncover the proteome of spheroids in human postmortem and mouse brains. Additionally, we established a human induced pluripotent stem cell (iPSC)-derived AD model enabling mechanistic investigation and optical electrophysiology. These complementary approaches revealed the subcellular molecular architecture of spheroids and identified abnormalities in key biological processes, including protein turnover, cytoskeleton dynamics and lipid transport. Notably, the PI3K/AKT/mTOR pathway, which regulates these processes, was activated in spheroids. Furthermore, phosphorylated mTOR levels in spheroids correlated with AD severity in humans. Notably, mTOR inhibition in iPSC-derived neurons and mice ameliorated spheroid pathology. Altogether, our study provides a multidisciplinary toolkit for investigating mechanisms and therapeutic targets for axonal pathology in neurodegeneration. Axonal spheroids disrupt neural circuits in Alzheimer’s disease. In this study, using subcellular proximity labeling proteomics in human brain and iPSC modeling, the authors link spheroid formation to dysregulated mTOR, cytoskeletal and lipid transport signaling.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 3","pages":"504-527"},"PeriodicalIF":17.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-025-00823-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598671","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

A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan

IF 17

Nature aging Pub Date : 2025-03-07 DOI: 10.1038/s43587-025-00830-4

Lorna Jayne, Aurora Lavin-Peter, Julian Roessler, Alexander Tyshkovskiy, Mateusz Antoszewski, Erika Ren, Aleksandar Markovski, Senmiao Sun, Hanqi Yao, Vijay G. Sankaran, Vadim N. Gladyshev, Robert T. Brooke, Steve Horvath, Eric C. Griffith, Sinisa Hrvatin

{"title":"A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan","authors":"Lorna Jayne, Aurora Lavin-Peter, Julian Roessler, Alexander Tyshkovskiy, Mateusz Antoszewski, Erika Ren, Aleksandar Markovski, Senmiao Sun, Hanqi Yao, Vijay G. Sankaran, Vadim N. Gladyshev, Robert T. Brooke, Steve Horvath, Eric C. Griffith, Sinisa Hrvatin","doi":"10.1038/s43587-025-00830-4","DOIUrl":"10.1038/s43587-025-00830-4","url":null,"abstract":"Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms of how torpor affects aging, and whether hypothermic and hypometabolic states can be induced to slow aging and increase healthspan, remain unknown. Here we demonstrate that the activity of a spatially defined neuronal population in the preoptic area, which has previously been identified as a torpor-regulating brain region, is sufficient to induce a torpor-like state (TLS) in mice. Prolonged induction of TLS slows epigenetic aging across multiple tissues and improves healthspan. We isolate the effects of decreased metabolic rate, long-term caloric restriction, and decreased core body temperature (Tb) on blood epigenetic aging and find that the decelerating effect of TLSs on aging is mediated by decreased Tb. Taken together, our findings provide novel mechanistic insight into the decelerating effects of torpor and hibernation on aging and support the growing body of evidence that Tb is an important mediator of the aging processes. Dissecting the effects of hypothermic and hypometabolic states on aging processes, the authors show that activation of neurons in the preoptic area induces a torpor-like state in mice that slows epigenetic aging and improves healthspan. These pro-longevity effects are mediated by reduced Tb, reinforcing evidence that Tb is a key mediator of aging processes.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 3","pages":"437-449"},"PeriodicalIF":17.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-025-00830-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588906","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

Accelerating the promise of geroscience through The Academy of Health & Lifespan Research.

IF 17

Nature aging Pub Date : 2025-03-07 DOI: 10.1038/s43587-025-00832-2

Nir Barzilai, Risa Starr, Eric Verdin, Laura J Niedernhofer, André Bertram, Gordon J Lithgow, Andrea B Maier

引用次数: 0

Cold is hot for slowing aging

IF 17

Nature aging Pub Date : 2025-03-07 DOI: 10.1038/s43587-025-00817-1

Matteo Cerri

引用次数: 0

Mitochondria-enriched hematopoietic stem cells exhibit elevated self-renewal capabilities, thriving within the context of aged bone marrow.

IF 17

Nature aging Pub 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

Single-cell immune aging clocks reveal inter-individual heterogeneity during infection and vaccination.

IF 17

Nature aging Pub Date : 2025-03-05 DOI: 10.1038/s43587-025-00819-z

Wenchao Li, Zhenhua Zhang, Saumya Kumar, Javier Botey-Bataller, Martijn Zoodsma, Ali Ehsani, Qiuyao Zhan, Ahmed Alaswad, Liang Zhou, Inge Grondman, Valerie Koeken, Jian Yang, Gang Wang, Sonja Volland, Tania O Crişan, Leo A B Joosten, Thomas Illig, Cheng-Jian Xu, Mihai G Netea, Yang Li

{"title":"Single-cell immune aging clocks reveal inter-individual heterogeneity during infection and vaccination.","authors":"Wenchao Li, Zhenhua Zhang, Saumya Kumar, Javier Botey-Bataller, Martijn Zoodsma, Ali Ehsani, Qiuyao Zhan, Ahmed Alaswad, Liang Zhou, Inge Grondman, Valerie Koeken, Jian Yang, Gang Wang, Sonja Volland, Tania O Crişan, Leo A B Joosten, Thomas Illig, Cheng-Jian Xu, Mihai G Netea, Yang Li","doi":"10.1038/s43587-025-00819-z","DOIUrl":"https://doi.org/10.1038/s43587-025-00819-z","url":null,"abstract":"Aging affects human immune system functionality, increasing susceptibility to immune-mediated diseases. While gene expression programs accurately reflect immune function, their relationship with biological immune aging and health status remains unclear. Here we developed robust, cell-type-specific aging clocks (sc-ImmuAging) for the myeloid and lymphoid immune cell populations in circulation within peripheral blood mononuclear cells, using single-cell RNA-sequencing data from 1,081 healthy individuals aged from 18 to 97 years. Application of sc-ImmuAging to transcriptome data of patients with COVID-19 revealed notable age acceleration in monocytes, which decreased during recovery. Furthermore, inter-individual variations in immune aging induced by vaccination were identified, with individuals exhibiting elevated baseline interferon response genes showing age rejuvenation in CD8+ T cells after BCG vaccination. sc-ImmuAging provides a powerful tool for decoding immune aging dynamics, offering insights into age-related immune alterations and potential interventions to promote healthy aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569292","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