Aging Cell最新文献_第9页

Prophylactic senolytic treatment in aged mice reduces seizure severity and improves survival from Status Epilepticus 对老年小鼠进行预防性溶酶治疗可降低癫痫发作的严重程度并提高癫痫状态的存活率

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-20 DOI: 10.1111/acel.14239

Tahiyana Khan, Abbas I. Hussain, Timothy P. Casilli, Logan Frayser, Michelle Cho, Gabrielle Williams, David McFall, Patrick A. Forcelli

{"title":"Prophylactic senolytic treatment in aged mice reduces seizure severity and improves survival from Status Epilepticus","authors":"Tahiyana Khan, Abbas I. Hussain, Timothy P. Casilli, Logan Frayser, Michelle Cho, Gabrielle Williams, David McFall, Patrick A. Forcelli","doi":"10.1111/acel.14239","DOIUrl":"10.1111/acel.14239","url":null,"abstract":"Increased vulnerability to seizures in aging has been well documented both clinically and in various models of aging in epilepsy. Seizures can exacerbate cognitive decline that is already prominent in aging. Senescent cells are thought to contribute to cognitive impairment in aging and clearing senescent cells with senolytic drugs improves cognitive function in animal models. It remains unclear whether senescent cells render the aged brain vulnerable to seizures. Here, we demonstrate that prophylactic senolytic treatment with Dasatinib and Quercetin (D&Q) reduced both seizure severity and mortality in aged C57BL/6J mice. We subjected the D&Q and VEH-treated aged mice to spatial memory testing before and after an acute seizure insult, Status Epilepticus [SE], which leads to epilepsy development. We found that senolytic therapy improved spatial memory before injury, however, spatial memory was not rescued after SE. Senescence-related proteins p16 and senescence-associated β-galactosidase were reduced in D&Q-treated aged mice. Our findings indicate that senescent cells increase seizure susceptibility in aging. Thus, prophylactically targeting senescent cells may prevent age-related seizure vulnerability.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141503918","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}

引用次数: 0

Aging-induced short-chain acyl-CoA dehydrogenase promotes age-related hepatic steatosis by suppressing lipophagy 衰老诱导的短链酰基-CoA脱氢酶通过抑制噬脂作用促进与衰老相关的肝脂肪变性。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-19 DOI: 10.1111/acel.14256

Dan Deng, Shanshan Yang, Xiaoqian Yu, Ruixue Zhou, Yin Liu, Hongmei Zhang, Daxin Cui, Xingrong Feng, Yanting Wu, Xiaocun Qi, Zhiguang Su

{"title":"Aging-induced short-chain acyl-CoA dehydrogenase promotes age-related hepatic steatosis by suppressing lipophagy","authors":"Dan Deng, Shanshan Yang, Xiaoqian Yu, Ruixue Zhou, Yin Liu, Hongmei Zhang, Daxin Cui, Xingrong Feng, Yanting Wu, Xiaocun Qi, Zhiguang Su","doi":"10.1111/acel.14256","DOIUrl":"10.1111/acel.14256","url":null,"abstract":"Hepatic steatosis, the first step in the development of nonalcoholic fatty liver disease (NAFLD), is frequently observed in the aging population. However, the underlying molecular mechanism remains largely unknown. In this study, we first employed GSEA enrichment analysis to identify short-chain acyl-CoA dehydrogenase (SCAD), which participates in the mitochondrial β-oxidation of fatty acids and may be associated with hepatic steatosis in elderly individuals. Subsequently, we examined SCAD expression and hepatic triglyceride content in various aged humans and mice and found that triglycerides were markedly increased and that SCAD was upregulated in aged livers. Our further evidence in SCAD-ablated mice suggested that SCAD deletion was able to slow liver aging and ameliorate aging-associated fatty liver. Examination of the molecular pathways by which the deletion of SCAD attenuates steatosis revealed that the autophagic degradation of lipid droplets, which was not detected in elderly wild-type mice, was maintained in SCAD-deficient old mice. This was due to the decrease in the production of acetyl-coenzyme A (acetyl-CoA), which is abundant in the livers of old wild-type mice. In conclusion, our findings demonstrate that the suppression of SCAD may prevent age-associated hepatic steatosis by promoting lipophagy and that SCAD could be a promising therapeutic target for liver aging and associated steatosis.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425795","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}

引用次数: 0

Age-dependent heat shock hormesis to HSF-1 deficiency suggests a compensatory mechanism mediated by the unfolded protein response and innate immunity in young Caenorhabditis elegans 年龄依赖性热休克激素对 HSF-1 缺乏的影响表明，年轻的秀丽隐杆线虫体内存在一种由未折叠蛋白反应和先天性免疫介导的补偿机制。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-19 DOI: 10.1111/acel.14246

Dániel Kovács, János Barnabás Biró, Saqib Ahmed, Márton Kovács, Tímea Sigmond, Bernadette Hotzi, Máté Varga, Viktor Vázsony Vincze, Umar Mohammad, Tibor Vellai, János Barna

{"title":"Age-dependent heat shock hormesis to HSF-1 deficiency suggests a compensatory mechanism mediated by the unfolded protein response and innate immunity in young Caenorhabditis elegans","authors":"Dániel Kovács, János Barnabás Biró, Saqib Ahmed, Márton Kovács, Tímea Sigmond, Bernadette Hotzi, Máté Varga, Viktor Vázsony Vincze, Umar Mohammad, Tibor Vellai, János Barna","doi":"10.1111/acel.14246","DOIUrl":"10.1111/acel.14246","url":null,"abstract":"The transcription factor HSF-1 (heat shock factor 1) acts as a master regulator of heat shock response in eukaryotic cells to maintain cellular proteostasis. The protein has a protective role in preventing cells from undergoing ageing, and neurodegeneration, and also mediates tumorigenesis. Thus, modulating HSF-1 activity in humans has a promising therapeutic potential for treating these pathologies. Loss of HSF-1 function is usually associated with impaired stress tolerance. Contrary to this conventional knowledge, we show here that inactivation of HSF-1 in the nematode Caenorhabditis elegans results in increased thermotolerance at young adult stages, whereas HSF-1 deficiency in animals passing early adult stages indeed leads to decreased thermotolerance, as compared to wild-type. Furthermore, a gene expression analysis supports that in young adults, distinct cellular stress response and immunity-related signaling pathways become induced upon HSF-1 deficiency. We also demonstrate that increased tolerance to proteotoxic stress in HSF-1-depleted young worms requires the activity of the unfolded protein response of the endoplasmic reticulum and the SKN-1/Nrf2-mediated oxidative stress response pathway, as well as an innate immunity-related pathway, suggesting a mutual compensatory interaction between HSF-1 and these conserved stress response systems. A similar compensatory molecular network is likely to also operate in higher animal taxa, raising the possibility of an unexpected outcome when HSF-1 activity is manipulated in humans.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416864","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}

引用次数: 0

Deficiency of SECTM1 impairs corneal wound healing in aging 缺乏 SECTM1 会影响衰老过程中角膜伤口的愈合。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-17 DOI: 10.1111/acel.14247

Jin Zhu, Xihong Lan, Kunlun Mo, Wang Zhang, Ying Huang, Jieying Tan, Li Wang, Jianping Ji, Qiong Ke, Hong Ouyang

{"title":"Deficiency of SECTM1 impairs corneal wound healing in aging","authors":"Jin Zhu, Xihong Lan, Kunlun Mo, Wang Zhang, Ying Huang, Jieying Tan, Li Wang, Jianping Ji, Qiong Ke, Hong Ouyang","doi":"10.1111/acel.14247","DOIUrl":"10.1111/acel.14247","url":null,"abstract":"The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self-renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity. A novel cytokine, Secreted and Transmembrane 1 (SECTM1), was found to facilitate corneal healing and was upregulated in young macaques upon wounding. Mechanistically, SECTM1 is essential for LSC migration and proliferation, and may partially function through Cell Division Cycle Associated 7 (CDCA7). Notably, the topical application of SECTM1 to aged wounded corneas dramatically promoted re-epithelialization and improved corneal transparency in both mice and macaques. Our work suggests that aging may impair the expression of healing response factors and injury repair in non-human primate corneas, and that SECTM1 application could potentially benefit corneal wound healing in clinical treatment.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416865","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}

引用次数: 0

Casual associations between brain structure and sarcopenia: A large-scale genetic correlation and mendelian randomization study 大脑结构与肌肉疏松症之间的偶然联系：大规模遗传相关性和亡羊补牢随机化研究。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-17 DOI: 10.1111/acel.14252

Guang Yang, Wenqing Xie, Bin Li, Guihu Zhao, Jinchen Li, Wenfeng Xiao, Yusheng Li

{"title":"Casual associations between brain structure and sarcopenia: A large-scale genetic correlation and mendelian randomization study","authors":"Guang Yang, Wenqing Xie, Bin Li, Guihu Zhao, Jinchen Li, Wenfeng Xiao, Yusheng Li","doi":"10.1111/acel.14252","DOIUrl":"10.1111/acel.14252","url":null,"abstract":"Sarcopenia presenting a critical challenge in population-aging healthcare. The elucidation of the interplay between brain structure and sarcopenia necessitates further research. The aim of this study is to explore the casual association between brain structure and sarcopenia. Linkage disequilibrium score regression (LDSC) was conducted to estimate the genetic correlations; MR was then performed to explore the causal relationship between Brain imaging-derived phenotypes (BIDPs) and three sarcopenia-related traits: handgrip strength, walking pace, and appendicular lean mass (ALM). The main analyses were conducted using the inverse-variance weighted method. Moreover, weighted median and MR–Egger were conducted as sensitivity analyses. Genetic association between 6.41% of BIDPs and ALM was observed, and 4.68% of BIDPs exhibited causal MR association with handgrip strength, 2.11% of BIDPs were causally associated with walking pace, and 2.04% of BIDPs showed causal association with ALM. Volume of ventromedial hypothalamus was associated with increased odds of handgrip strength (OR: 1.18, 95% CI: 1.02 to 1.37) and ALM (OR: 1.05, 95% CI: 1.01 to 1.09). Mean thickness of G-pariet-inf-Angular was associated with decreased odds of handgrip strength (OR: 0.83, 95% CI: 0.70 to 0.97) and walking pace (OR: 0.97, 95% CI: 0.93 to 0.99). As part of the brain structure forward causally influences sarcopenia, which may provide new perspectives for the prevention of sarcopenia and offer valuable insights for further research on the brain-muscle axis.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141329809","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}

引用次数: 0

Age-specific and compartment-dependent changes in mitochondrial homeostasis and cytoplasmic viscosity in mouse peripheral neurons 小鼠外周神经元线粒体稳态和胞质粘度的变化具有年龄特异性和分区依赖性。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-17 DOI: 10.1111/acel.14250

James N. Sleigh, Francesca Mattedi, Sandy Richter, Emily Annuario, Kristal Ng, I. Emilie Steinmark, Iveta Ivanova, István L. Darabán, Parth P. Joshi, Elena R. Rhymes, Shirwa Awale, Gokhan Yahioglu, Jacqueline C. Mitchell, Klaus Suhling, Giampietro Schiavo, Alessio Vagnoni

{"title":"Age-specific and compartment-dependent changes in mitochondrial homeostasis and cytoplasmic viscosity in mouse peripheral neurons","authors":"James N. Sleigh, Francesca Mattedi, Sandy Richter, Emily Annuario, Kristal Ng, I. Emilie Steinmark, Iveta Ivanova, István L. Darabán, Parth P. Joshi, Elena R. Rhymes, Shirwa Awale, Gokhan Yahioglu, Jacqueline C. Mitchell, Klaus Suhling, Giampietro Schiavo, Alessio Vagnoni","doi":"10.1111/acel.14250","DOIUrl":"10.1111/acel.14250","url":null,"abstract":"Mitochondria are dynamic bioenergetic hubs that become compromised with age. In neurons, declining mitochondrial axonal transport has been associated with reduced cellular health. However, it is still unclear to what extent the decline of mitochondrial transport and function observed during ageing are coupled, and if somal and axonal mitochondria display compartment-specific features that make them more susceptible to the ageing process. It is also not known whether the biophysical state of the cytoplasm, thought to affect many cellular functions, changes with age to impact mitochondrial trafficking and homeostasis. Focusing on the mouse peripheral nervous system, we show that age-dependent decline in mitochondrial trafficking is accompanied by reduction of mitochondrial membrane potential and intramitochondrial viscosity, but not calcium buffering, in both somal and axonal mitochondria. Intriguingly, we observe a specific increase in cytoplasmic viscosity in the neuronal cell body, where mitochondria are most polarised, which correlates with decreased cytoplasmic diffusiveness. Increasing cytoplasmic crowding in the somatic compartment of DRG neurons grown in microfluidic chambers reduces mitochondrial axonal trafficking, suggesting a mechanistic link between the regulation of cytoplasmic viscosity and mitochondrial dynamics. Our work provides a reference for studying the relationship between neuronal mitochondrial homeostasis and the viscoelasticity of the cytoplasm in a compartment-dependent manner during ageing.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141329808","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}

引用次数: 0

Correction to “Targeting amphiregulin (AREG) derived from senescent stromal cells diminishes cancer resistance and averts programmed cell death 1 ligand (PD-L1)-mediated immunosuppression” 对 "靶向来自衰老基质细胞的两性胰岛素（AREG）可减轻癌症抗药性并避免程序性细胞死亡 1 配体（PD-L1）介导的免疫抑制 "的更正："靶向来自衰老基质细胞的两性胰岛素（AREG）可减轻癌症抗药性并避免程序性细胞死亡 1 配体（PD-L1）介导的免疫抑制。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-14 DOI: 10.1111/acel.14248

{"title":"Correction to “Targeting amphiregulin (AREG) derived from senescent stromal cells diminishes cancer resistance and averts programmed cell death 1 ligand (PD-L1)-mediated immunosuppression”","authors":"","doi":"10.1111/acel.14248","DOIUrl":"10.1111/acel.14248","url":null,"abstract":"Xu Q, Long Q, Zhu D, et al. Targeting amphiregulin (AREG) derived from senescent stromal cells diminishes cancer resistance and averts programmed cell death 1 ligand (PD-L1)-mediated immunosuppression. Aging Cell. 2019;18:e13027. https://doi.org/10.1111/acel.13027During the data organization and author preparation of this manuscript, there were a couple of errors inadvertently incorporated into the manuscript and not recognized effectively during the proofing stage. We noticed that the following item needs to be appropriately corrected.Figure 5h. Representative IHC images of caspase 3 (cleaved) in tumors at the end of therapeutic regimes. The “Placebo-treated AREG mAb” and “MIT-treated Cetuximab” images were mistakenly picked up by authors to organize the original panel. As a necessary effort, the authors have now located the appropriate representative images and corrected this figure. Please refer to the updated Figure 5h.All other parts of this article remain intact, valid, and unchanged. The authors sincerely regret the error and would like to apologize for any inconvenience this may have caused. The corrected figure is provided below. We apologize for this error.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 7","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316170","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}

引用次数: 0

TAF15 downregulation contributes to the benefits of physical training on dendritic spines and working memory in aged mice TAF15下调有助于体育训练对老年小鼠树突棘和工作记忆的益处。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-14 DOI: 10.1111/acel.14244

Yun He, Benju Liu, Fu-Yuan Yang, Qun Yang, Benke Xu, Lian Liu, Yuncai Chen

{"title":"TAF15 downregulation contributes to the benefits of physical training on dendritic spines and working memory in aged mice","authors":"Yun He, Benju Liu, Fu-Yuan Yang, Qun Yang, Benke Xu, Lian Liu, Yuncai Chen","doi":"10.1111/acel.14244","DOIUrl":"10.1111/acel.14244","url":null,"abstract":"Moderate physical training has been shown to hinder age-related memory decline. While the benefits of physical training on hippocampal memory function are well-documented, little is known about its impact on working memory, which is linked to the prelimbic cortex (PrL), one major subdivision of the prefrontal cortex. Here, we examined the effects of physical training on spatial working memory in a well-established animal model of physical training, starting at 16 months of age and continuing for 5 months (running wheel 1 h/day and 5 days/week). This training strategy improved spatial working memory in aged mice (22-month-old), which was accompanied by an increased spine density and a lower TAF15 expression in the PrL. Specifically, physical training affected both thin and mushroom-type spines on PrL pyramidal cells, and prevented age-related loss of spines on selective segments of apical dendritic branches. Correlation analysis revealed that increased TAF15-expression was detrimental to the dendritic spines. However, physical training downregulated TAF15 expression in the PrL, preserving the dendritic spines on PrL pyramidal cells and improving working memory in trained aged mice. When TAF15 was overexpressed in the PrL via a viral approach, the benefits of physical training on the dendritic spines and working memory were abolished. These data suggest that physical training at a moderate pace might downregulate TAF15 expression in the PrL, which favors the dendritic spines on PrL pyramidal cells, thereby improving spatial working memory.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316171","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}

引用次数: 0

Growth hormone-releasing hormone deficiency confers extended lifespan and metabolic resilience during high-fat feeding in mid and late life 生长激素释放激素缺乏症可延长寿命，并在中后期高脂肪喂养期间提高代谢恢复能力。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-12 DOI: 10.1111/acel.14238

Joseph Adkins-Jablonsky, Alexander Tate Lasher, Amit Patki, Akash Nagarajan, Liou Y. Sun

{"title":"Growth hormone-releasing hormone deficiency confers extended lifespan and metabolic resilience during high-fat feeding in mid and late life","authors":"Joseph Adkins-Jablonsky, Alexander Tate Lasher, Amit Patki, Akash Nagarajan, Liou Y. Sun","doi":"10.1111/acel.14238","DOIUrl":"10.1111/acel.14238","url":null,"abstract":"Growth hormone-releasing hormone-deficient (GHRH-KO) mice have previously been characterized by lower body weight, disproportionately high body fat accumulation, preferential metabolism of lipids compared to carbohydrates, improved insulin sensitivity, and an extended lifespan. That these mice are long-lived and insulin-sensitive conflicts with the notion that adipose tissue accumulation drives the health detriments associated with obesity (i.e., diabetes), and indicates that GH signaling may be necessary for the development of adverse effects linked to obesity. This prompts investigation into the ultimate effect of diet-induced obesity on the lifespan of these long-lived mice. To this end, we initiated high-fat feeding in mid and late-life in GHRH-KO and wild-type (WT) mice. We carried out extensive lifespan analysis coupled with glucose/insulin tolerance testing and indirect calorimetry to gauge the metabolic effect of high-fat dietary stress through adulthood on these mice. We show that under high-fat diet (HFD) conditions, GHRH-KO mice display extended lifespans relative to WT controls. We also show that GHRH-KO mice are more insulin-sensitive and display less dramatic changes in their metabolism relative to WT mice, with GHRH-KO mice fed HFD displaying respiratory exchange ratios and glucose oxidation rates comparable to control-diet fed GHRH-KO mice, while WT mice fed HFD showed significant reductions in these parameters. Our results indicate that GH deficiency protects against the adverse effects of diet-induced obesity in later life.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309673","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}

引用次数: 0

Anatomical Society Research Studentships 2024/25 解剖学会 2024/25 年度研究奖学金

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-11 DOI: 10.1111/acel.14253

引用次数: 0