Aging Biology最新文献_第2页

Restricting the Possibilities for Mechanisms of Calorie Restriction 限制热量限制机制的可能性

Aging Biology Pub Date : 2023-06-29 DOI: 10.59368/agingbio.20230006

Peter D. Adams

引用次数: 0

Senolytics Reduce Endothelial Cell DNA Damage and Telomere Dysfunction Despite Reductions in Telomere Length. 利用单细胞全基因组测序分析衰老细胞的体细胞突变

Aging Biology Pub Date : 2023-01-01 Epub Date: 2023-06-27 DOI: 10.59368/agingbio.20230007

Samuel I Bloom, Eric Tuday, Torikul Islam, Venkateswara R Gogulamudi, Lisa A Lesniewski, Anthony J Donato

{"title":"Senolytics Reduce Endothelial Cell DNA Damage and Telomere Dysfunction Despite Reductions in Telomere Length.","authors":"Samuel I Bloom, Eric Tuday, Torikul Islam, Venkateswara R Gogulamudi, Lisa A Lesniewski, Anthony J Donato","doi":"10.59368/agingbio.20230007","DOIUrl":"10.59368/agingbio.20230007","url":null,"abstract":"Aging results in cellular damage that can induce cell cycle arrest known as cellular senescence. Endothelial cells are one of the first cell types to become senescent in advancing age and contribute to age-related cardiovascular diseases. Drugs known as senolytics reduce endothelial cell senescence in cell culture. From a translational perspective, a key question is whether this occurs in vivo and if remaining cells appear healthier and display fewer hallmarks of cellular aging. In this study, we treated old mice with the senolytic cocktail dasatinib and quercetin (D+Q) or a vehicle control. In 24-month-old mice, D+Q treatment reduced p21 gene expression in carotid artery endothelial cells, indicative of reductions in senescence. In lung endothelial cells, we examined DNA damage, telomere dysfunction (DNA damage signaling at telomeres), and telomere length, which are hallmarks of aging associated with senescence and other deleterious effects on cellular function. D+Q treatment resulted in fewer endothelial cells with DNA damage and dysfunctional telomeres. Surprisingly, D+Q reduced endothelial cell telomere length, yet this did not result in critically short telomeres and thus telomere dysfunction. Mice have longer telomeres than humans; therefore, future studies on the effect of senolytics on telomere length are warranted. Collectively, this study provides important evidence on the effect of senolytics, including that they clear senescent endothelial cells in vivo, which reduces DNA damage and telomere dysfunction. These data indicate that the clearing of senescent endothelial cells in old age leaves behind a population of cells that exhibit fewer hallmarks of vascular aging.","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89115398","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

Aging Rate Indicators: Speedometers for Aging Research in Mice. 衰老率指标:小鼠衰老研究的速度计。

Aging Biology Pub Date : 2023-01-01 DOI: 10.59368/agingbio.20230003

Richard A Miller, Xinna Li, Gonzalo Garcia

{"title":"Aging Rate Indicators: Speedometers for Aging Research in Mice.","authors":"Richard A Miller, Xinna Li, Gonzalo Garcia","doi":"10.59368/agingbio.20230003","DOIUrl":"https://doi.org/10.59368/agingbio.20230003","url":null,"abstract":"A \"biomarker of aging\" is conceptualized as an index of how far an individual has moved along the path from youth to old age. In contrast, an aging rate indicator (ARI) represents a measure of speed, rather than distance, that is, a measure of how rapidly the individual is moving toward the phenotypic changes typical of old age. This essay presents and reviews recent data suggesting common characteristics of slow-aging mice, whether the slowed aging is caused by a mutant allele, the calorie restriction diet, or drugs that slow aging and extend mean and maximal lifespan. Some of the candidate ARIs, shared by nine varieties of slow-aging mice, are physiological changes seen in fat, fat-associated macrophages, muscle, liver, brain, and plasma. Others are molecular measurements, reflecting activity of mTORC1, selective mRNA translation, or each of six MAP kinases in two distinct MAPK cascades in liver, muscle, or kidney. Changes in ARIs are notable in young adult mice after 8 months of drug or diet exposure, are detectable in mutant mice at least as early as 4-6 months of age, and persist until at least 18-22 months. Many of the candidate ARIs are thought to play an influential role in cognition, inflammation, exercise responses, and control of metabolic rate, and are thus plausible as modulators of age-related physiological and neurological illnesses. In principle, screening for drugs that induce alterations in ARIs in normal young adult mice might facilitate the search for preventive medicines that can retard aging and late-life illnesses in mice or in human populations.","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486275/pdf/nihms-1928132.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10588057","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: 3

FGF21 has a sex-specific role in calorie-restriction-induced beiging of white adipose tissue in mice. FGF21在卡路里限制诱导的小鼠白色脂肪组织粗化过程中具有性别特异性。

Aging Biology Pub Date : 2022-01-01

Mariah F Calubag, Ismail Ademi, Chung-Yang Yeh, Reji Babygirija, Heidi H Pak, Alyssa M Bhoopat, Ildiko Kasza, Cara L Green, Michelle M Sonsalla, Dudley W Lamming

{"title":"FGF21 has a sex-specific role in calorie-restriction-induced beiging of white adipose tissue in mice.","authors":"Mariah F Calubag, Ismail Ademi, Chung-Yang Yeh, Reji Babygirija, Heidi H Pak, Alyssa M Bhoopat, Ildiko Kasza, Cara L Green, Michelle M Sonsalla, Dudley W Lamming","doi":"","DOIUrl":"","url":null,"abstract":"Calorie restriction (CR) promotes healthspan and extends the lifespan of diverse organisms, including mice, and there is intense interest in understanding the molecular mechanisms by which CR functions. Some studies have demonstrated that CR induces fibroblast growth factor 21 (FGF21), a hormone that regulates energy balance and that when overexpressed, promotes metabolic health and longevity in mice, but the role of FGF21 in the response to CR has not been fully investigated. We directly examined the role of FGF21 in the physiological and metabolic response to a CR diet by feeding Fgf21-/- and wild-type control mice either ad libitum (AL) diet or a 30% CR diet for 15 weeks. Here, we find that FGF21 is largely dispensable for CR-induced improvements in body composition and energy balance, but that lack of Fgf21 blunts CR-induced changes aspects of glucose regulation and insulin sensitivity in females. Surprisingly, despite not affecting CR-induced changes in energy expenditure, loss of Fgf21 significantly blunts CR-induced beiging of white adipose tissue in male but not female mice. Our results shed new light on the molecular mechanisms involved in the beneficial effects of a CR diet, clarify that FGF21 is largely dispensable for the metabolic effects of a CR diet, and highlight a sex-dependent role for FGF21 in the molecular adaptation of white adipose tissue to CR.","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10181818/pdf/nihms-1864795.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9873047","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