Aging Cell最新文献_第3页

Comprehensive evaluation of lifespan-extending molecules in C. elegans 线虫寿命延长分子的综合评价。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-24 DOI: 10.1111/acel.14424

Grace B. Phelps, Jonas Morin, Carla Pinto, Lucas Schoenfeldt, Sebastien Guilmot, Alejandro Ocampo, Kevin Perez

{"title":"Comprehensive evaluation of lifespan-extending molecules in C. elegans","authors":"Grace B. Phelps, Jonas Morin, Carla Pinto, Lucas Schoenfeldt, Sebastien Guilmot, Alejandro Ocampo, Kevin Perez","doi":"10.1111/acel.14424","DOIUrl":"10.1111/acel.14424","url":null,"abstract":"The nematode C. elegans has long served as a gold-standard model organism in aging research, particularly since the discovery of long-lived mutants in conserved aging pathways including daf-2 (IGF1) and age-1 (PI3K). Its short lifespan and small size make it highly suitable for high-throughput experiments. While numerous molecules have been tested for their effects on C. elegans lifespan, consensus is still lacking regarding the most effective and reproducible compounds. Confounding effects, especially those related to drug-bacteria interactions, remain a contentious issue in the literature. In this study, we evaluated 16 of the most frequently reported lifespan-extending molecules in C. elegans, examining their effects on lifespan with two different diets (live and UV-killed OP50). In addition, we assessed the compounds' impact on bacterial growth, their effects on various nematode strains, and the impact of the starting age of treatment. Our findings first confirmed robust lifespan extension by many, but not all, of the 16 tested compounds from the literature, and revealed that some of them could be combined to obtain additive effects. Additionally, we showed that some of these compounds also extend lifespan in the fly D. melanogaster, demonstrating a conserved effect across species. Finally, by expanding our screen to a broader pool of molecules, we identified novel lifespan-extending compounds in C. elegans.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Aging and Cancer—Inextricably Linked Across the Lifespan 衰老和癌症在人的一生中有着千丝万缕的联系。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-21 DOI: 10.1111/acel.14483

James DeGregori, Katherine J. Seidl, Monty Montano

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Correction to “Rutin is a Potent Senomorphic Agent to Target Senescent Cells and Can Improve Chemotherapeutic Efficacy” 更正“芦丁是一种针对衰老细胞的强效Senomorphic Agent，可以提高化疗疗效”。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-17 DOI: 10.1111/acel.14488

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Higher Intron Retention Levels in Female Alzheimer's Brains May Be Linked to Disease Prevalence 女性阿尔茨海默氏症患者大脑中较高的内含子保留水平可能与疾病患病率有关。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-13 DOI: 10.1111/acel.14457

Ching-Thong Choo, Chao-Yong Leow, Chin-Tong Ong

{"title":"Higher Intron Retention Levels in Female Alzheimer's Brains May Be Linked to Disease Prevalence","authors":"Ching-Thong Choo, Chao-Yong Leow, Chin-Tong Ong","doi":"10.1111/acel.14457","DOIUrl":"10.1111/acel.14457","url":null,"abstract":"Multimodal study of Alzheimer's disease (AD) dorsolateral prefrontal cortex (DLPFC) showed AD-related aberrant intron retention (IR) and proteomic changes not observed at the RNA level. However, the role of sex and how IR may impact the proteome are unclear. Analysis of DLPFC transcriptome showed a clear sex-biased pattern where female AD had 1645 elevated IR events compared to 80 in male AD DLPFC. Increased IR is correlated with lower mRNA levels, suggestive of nonsense-mediated mRNA decay. Two hundred thirty-three mRNAs with elevated IR in females were curated AD genes enriched for ubiquitin-like protein ligase and Tau protein binding. Increased IR genes in combined sex and female AD cohorts showed significant changes in their protein expression patterns with 11%–24% of them differential expressed proteins (DEP), alluding to the regulation of AD proteome by IR independent of RNA level. Upregulated DEPs in male AD were linked to RNA splicing that may prevent aberrant IR, whereas in female AD, they overlapped significantly more with the MAPK/metabolism module associated with cognitive decline. IR genes appeared to be significantly downregulated in specific female AD inhibitory and excitatory neurons compared to control. Differentially retained introns in female AD have elevated H3K27ac marks, strong CTCF binding at their flanking exons, and enriched for PABPC1 motif. Given that H3K27ac is repressive over gene bodies in aged brain and CTCF impedes transcription elongation, their binding patterns can delay co-transcriptional recruitment of spliceosome to cause IR, which may in turn contribute to different trajectories of AD pathology in women.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Cross-tissue comparison of epigenetic aging clocks in humans 人类表观遗传衰老时钟的跨组织比较。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-09 DOI: 10.1111/acel.14451

Abner T. Apsley, Qiaofeng Ye, Avshalom Caspi, Christopher Chiaro, Laura Etzel, Waylon J. Hastings, Christine M. Heim, John Kozlosky, Jennie G. Noll, Hannah M. C. Schreier, Chad E. Shenk, Karen Sugden, Idan Shalev

{"title":"Cross-tissue comparison of epigenetic aging clocks in humans","authors":"Abner T. Apsley, Qiaofeng Ye, Avshalom Caspi, Christopher Chiaro, Laura Etzel, Waylon J. Hastings, Christine M. Heim, John Kozlosky, Jennie G. Noll, Hannah M. C. Schreier, Chad E. Shenk, Karen Sugden, Idan Shalev","doi":"10.1111/acel.14451","DOIUrl":"10.1111/acel.14451","url":null,"abstract":"Epigenetic clocks are a common group of tools used to measure biological aging—the progressive deterioration of cells, tissues, and organs. Epigenetic clocks have been trained almost exclusively using blood-based tissues, but there is growing interest in estimating epigenetic age using less-invasive oral-based tissues (i.e., buccal or saliva) in both research and commercial settings. However, differentiated cell types across body tissues exhibit unique DNA methylation landscapes and age-related alterations to the DNA methylome. Applying epigenetic clocks derived from blood-based tissues to estimate epigenetic age of oral-based tissues may introduce biases. We tested the within-person comparability of common epigenetic clocks across five tissue types: buccal epithelial, saliva, dry blood spots, buffy coat (i.e., leukocytes), and peripheral blood mononuclear cells. We tested 284 distinct tissue samples from 83 individuals aged 9–70 years. Overall, there were significant within-person differences in epigenetic clock estimates from oral-based versus blood-based tissues, with average differences of almost 30 years observed in some age clocks. In addition, most epigenetic clock estimates of blood-based tissues exhibited low correlation with estimates from oral-based tissues despite controlling for cellular proportions and other technical factors. Notably, the Skin and Blood clock exhibited the greatest concordance across all tissue types, indicating its unique ability to estimate chronological age in oral- and blood-based tissues. Our findings indicate that application of blood-derived epigenetic clocks in oral-based tissues may not yield comparable estimates of epigenetic age, highlighting the need for careful consideration of tissue type when estimating epigenetic age.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-08 DOI: 10.1111/acel.14479

Todd W. Dowrey, Samuel F. Cranston, Nicholas Skvir, Yvonne Lok, Brian Gould, Bradley Petrowitz, Daniel Villar, Jidong Shan, Marianne James, Mark Dodge, Anna C. Belkina, Richard M. Giadone, Sofiya Milman, Paola Sebastiani, Thomas T. Perls, Stacy L. Andersen, George J. Murphy

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Additional Cover 额外的封面

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-08 DOI: 10.1111/acel.14480

Nathalie Launay, Maria Espinosa-Alcantud, Edgard Verdura, Gorka Fernández-Eulate, Jon Ondaro, Pablo Iruzubieta, Maria Marsal, Agatha Schlüter, Montserrat Ruiz, Stephane Fourcade, Agustí Rodríguez-Palmero, Miren Zulaica, Andone Sistiaga, Garazi Labayru, Pablo Loza-Alvarez, Alejandro Vaquero, Adolfo Lopez de Munain, Aurora Pujol

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Featured Cover 了封面

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-08 DOI: 10.1111/acel.14478

Yu Li, Jinxin Qi, Linhong Guo, Xian Jiang, Gu He

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Dietary cinnamon promotes longevity and extends healthspan via mTORC1 and autophagy signaling 膳食肉桂通过mTORC1和自噬信号促进长寿和延长健康寿命。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-06 DOI: 10.1111/acel.14448

Yuling Guo, Qing Zhang, Bi Zhang, Tong Pan, Elizabeth A. Ronan, Anthony Huffman, Yongqun He, Ken Inoki, Jianfeng Liu, X.Z. Shawn Xu

{"title":"Dietary cinnamon promotes longevity and extends healthspan via mTORC1 and autophagy signaling","authors":"Yuling Guo, Qing Zhang, Bi Zhang, Tong Pan, Elizabeth A. Ronan, Anthony Huffman, Yongqun He, Ken Inoki, Jianfeng Liu, X.Z. Shawn Xu","doi":"10.1111/acel.14448","DOIUrl":"10.1111/acel.14448","url":null,"abstract":"Cinnamon, renowned for its aromatic flavor, represents one of the most widely used spices worldwide. Cinnamon is also considered beneficial to human health with therapeutic potential for treating various diseases, ranging from diabetes and cancer to neurodegenerative diseases. However, the mechanisms underlying cinnamon's health benefits remain elusive. It is also unclear whether cinnamon has any role in aging. Using C. elegans as a model, here we show that feeding worms cinnamaldehyde (CA), the active ingredient in cinnamon oil, prolongs longevity. CA also promotes stress resistance and reduces β-Amyloid toxicity in a C. elegans model of Alzheimer's disease. Mechanistically, CA exerts its beneficial effects through mTORC1 and autophagy signaling. Interestingly, CA promotes longevity by inducing a dietary restriction-like state without affecting food intake, suggesting CA as a dietary restriction mimetic. In human cells, CA exerts a similar effect on mTORC1 and autophagy signaling, suggesting a conserved mechanism. Our results demonstrate that dietary cinnamon promotes both lifespan and healthspan and does so by regulating mTORC1 and autophagy signaling.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Immunotherapeutic targeting of aging-associated isoDGR motif in chronic lung inflammation 衰老相关的isoDGR基序在慢性肺部炎症中的免疫治疗靶向。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-05 DOI: 10.1111/acel.14425

Pazhanichamy Kalailingam, SoFong Cam Ngan, Ranjith Iyappan, Afra Nehchiri, Khalilatul-Hanisah Mohd-Kahliab, Benjamin Sian Teck Lee, Bhargy Sharma, Radek Machan, Sint Thida Bo, Emma S. Chambers, Val A. Fajardo, Rebecca E. K. Macpherson, Jian Liu, Panagiota Klentrou, Evangelia Litsa Tsiani, Kah Leong Lim, I. Hsin Su, Yong-Gui Gao, A. Mark Richar, Raj N. Kalaria, Christopher P. Chen, Cynthia Balion, Dominique de Kleijn, Neil E. McCarthy, Siu Kwan Sze

{"title":"Immunotherapeutic targeting of aging-associated isoDGR motif in chronic lung inflammation","authors":"Pazhanichamy Kalailingam, SoFong Cam Ngan, Ranjith Iyappan, Afra Nehchiri, Khalilatul-Hanisah Mohd-Kahliab, Benjamin Sian Teck Lee, Bhargy Sharma, Radek Machan, Sint Thida Bo, Emma S. Chambers, Val A. Fajardo, Rebecca E. K. Macpherson, Jian Liu, Panagiota Klentrou, Evangelia Litsa Tsiani, Kah Leong Lim, I. Hsin Su, Yong-Gui Gao, A. Mark Richar, Raj N. Kalaria, Christopher P. Chen, Cynthia Balion, Dominique de Kleijn, Neil E. McCarthy, Siu Kwan Sze","doi":"10.1111/acel.14425","DOIUrl":"10.1111/acel.14425","url":null,"abstract":"Accumulation of damaged biomolecules in body tissues is the primary cause of aging and age-related chronic diseases. Since this damage often occurs spontaneously, it has traditionally been regarded as untreatable, with typical therapeutic strategies targeting genes or enzymes being ineffective in this domain. In this report, we demonstrate that an antibody targeting the isoDGR damage motif in lung tissue can guide immune clearance of harmful damaged proteins in vivo, effectively reducing age-linked lung inflammation. We observed age-dependent accumulation of the isoDGR motif in human lung tissues, as well as an 8-fold increase in isoDGR-damaged proteins in lung fibrotic tissues compared with healthy tissue. This increase was accompanied by marked infiltration of CD68+/CD11b + macrophages, consistent with a role for isoDGR in promoting chronic inflammation. We therefore assessed isoDGR function in mice that were either naturally aged or lacked the isoDGR repair enzyme. IsoDGR-protein accumulation in mouse lung tissue was strongly correlated with chronic inflammation, pulmonary edema, and hypoxemia. This accumulation also induced mitochondrial and ribosomal dysfunction, in addition to features of cellular senescence, thereby contributing to progressive lung damage over time. Importantly, treatment with anti-isoDGR antibody was able to reduce these molecular features of disease and significantly reduced lung pathology in vivo.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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