Aging Cell最新文献_第4页

Aging-associated atrial fibrillation: A comprehensive review focusing on the potential mechanisms 与衰老相关的心房颤动：以潜在机制为重点的全面综述。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-08-12 DOI: 10.1111/acel.14309

Meng-Fei Wang, Can Hou, Fang Jia, Cheng-Hao Zhong, Cong Xue, Jian-Jun Li

{"title":"Aging-associated atrial fibrillation: A comprehensive review focusing on the potential mechanisms","authors":"Meng-Fei Wang, Can Hou, Fang Jia, Cheng-Hao Zhong, Cong Xue, Jian-Jun Li","doi":"10.1111/acel.14309","DOIUrl":"10.1111/acel.14309","url":null,"abstract":"Atrial fibrillation (AF) has been receiving a lot of attention from scientists and clinicians because it is an extremely common clinical condition. Due to its special hemodynamic changes, AF has a high rate of disability and mortality. So far, although AF has some therapeutic means, it is still an incurable disease because of its complex risk factors and pathophysiologic mechanisms, which is a difficult problem for global public health. Age is an important independent risk factor for AF, and the incidence of AF increases with age. To date, there is no comprehensive review on aging-associated AF. In this review, we systematically discuss the pathophysiologic evidence for aging-associated AF, and in particular explore the pathophysiologic mechanisms of mitochondrial dysfunction, telomere attrition, cellular senescence, disabled macroautophagy, and gut dysbiosis involved in recent studies with aging-associated AF. We hope that by exploring the various dimensions of aging-associated AF, we can better understand the specific relationship between age and AF, which may be crucial for innovative treatments of aging-associated AF.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970030","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

Wide-ranging genetic variation in sensitivity to rapamycin in Drosophila melanogaster 黑腹果蝇对雷帕霉素敏感性的广泛遗传变异

IF 7.8 1区医学

Aging Cell Pub Date : 2024-08-12 DOI: 10.1111/acel.14292

Benjamin R. Harrison, Mitchell B. Lee, Shufan Zhang, Bill Young, Kenneth Han, Jiranut Sukomol, Vanessa Paus, Sarina Tran, David Kim, Hannah Fitchett, Yu-Chen Pan, Philmon Tesfaye, Alia W. Johnson, Xiaqing Zhao, Danijel Djukovic, Daniel Raftery, Daniel E. L. Promislow

{"title":"Wide-ranging genetic variation in sensitivity to rapamycin in Drosophila melanogaster","authors":"Benjamin R. Harrison, Mitchell B. Lee, Shufan Zhang, Bill Young, Kenneth Han, Jiranut Sukomol, Vanessa Paus, Sarina Tran, David Kim, Hannah Fitchett, Yu-Chen Pan, Philmon Tesfaye, Alia W. Johnson, Xiaqing Zhao, Danijel Djukovic, Daniel Raftery, Daniel E. L. Promislow","doi":"10.1111/acel.14292","DOIUrl":"10.1111/acel.14292","url":null,"abstract":"The progress made in aging research using laboratory organisms is undeniable. Yet, with few exceptions, these studies are conducted in a limited number of isogenic strains. The path from laboratory discoveries to treatment in human populations is complicated by the reality of genetic variation in nature. To model the effect of genetic variation on the action of the drug rapamycin, here we use the growth of Drosophila melanogaster larvae. We screened 140 lines from the Drosophila Genetic References Panel for the extent of developmental delay and found wide-ranging variation in their response, from lines whose development time is nearly doubled by rapamycin, to those that appear to be completely resistant. Sensitivity did not associate with any single genetic marker, nor with any gene. However, variation at the level of genetic pathways was associated with rapamycin sensitivity and might provide insight into sensitivity. In contrast to the genetic analysis, metabolomic analysis showed a strong response of the metabolome to rapamycin, but only among the sensitive larvae. In particular, we found that rapamycin altered levels of amino acids in sensitive larvae, and in a direction strikingly similar to the metabolome response to nutrient deprivation. This work demonstrates the need to evaluate interventions across genetic backgrounds and highlights the potential of omic approaches to reveal biomarkers of drug efficacy and to shed light on mechanisms underlying sensitivity to interventions aimed at increasing lifespan.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 11","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970031","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

β-Hydroxybutyrate enhances chondrocyte mitophagy and reduces cartilage degeneration in osteoarthritis via the HCAR2/AMPK/PINK1/Parkin pathway β-羟丁酸通过HCAR2/AMPK/PINK1/Parkin途径增强软骨细胞有丝分裂并减少骨关节炎软骨退化。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-08-09 DOI: 10.1111/acel.14294

Huangming Zhuang, Xunshan Ren, Yuelong Zhang, Huajie Li, Panghu Zhou

{"title":"β-Hydroxybutyrate enhances chondrocyte mitophagy and reduces cartilage degeneration in osteoarthritis via the HCAR2/AMPK/PINK1/Parkin pathway","authors":"Huangming Zhuang, Xunshan Ren, Yuelong Zhang, Huajie Li, Panghu Zhou","doi":"10.1111/acel.14294","DOIUrl":"10.1111/acel.14294","url":null,"abstract":"Osteoarthritis (OA) is widely recognized as the prevailing joint disease associated with aging. The ketogenic diet (KD) has been postulated to impede the advancement of various inflammatory ailments. β-Hydroxybutyrate (βOHB), a prominent constituent of ketone bodies, has recently been proposed to possess crucial signaling capabilities. In this study, we propose to explore the role and mechanism of βOHB in OA. Tissue staining and inflammatory factor assay were employed to evaluate the impacts of KD and βOHB on OA rats. The oxidative stress conditions in chondrocytes were induced using tert-butyl hydroperoxide (TBHP). The mechanisms were determined using the siRNA of hydroxycarboxylic acid receptor 2 (HCAR2), the antagonist of adenosine monophosphate-activated protein kinase (AMPK), and the inhibitor of mitophagy. The administration of KD demonstrated a reduction in pathological damage to cartilage, as well as a decrease in plasma levels of inflammatory factors. Furthermore, it resulted in an increase in the concentration of βOHB in the blood and synovial fluid. In vitro experiments showed that βOHB facilitated mitophagy and adenosine triphosphate production. Besides, βOHB mitigated chondrocyte senescence, inflammatory factors secretion, extracellular matrix degradation, and apoptosis induced by TBHP. Subsequent investigations indicated that the protective effects of βOHB were no longer observed following the knockdown of HCAR2, the antagonist of AMPK, or the inhibitor of mitophagy. Moreover, in vivo studies suggested that βOHB played a protective role by targeting the HCAR2-AMPK-PINK1 axis. In conclusion, βOHB enhanced chondrocyte mitophagy through the HCAR2/AMPK/PINK1/Parkin pathway, offering a potential therapeutic approach for the treatment of OA.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 11","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141910895","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

miR-203-3p promotes senescence of mouse bone marrow mesenchymal stem cells via downregulation of Pbk miR-203-3p 通过下调 Pbk 促进小鼠骨髓间充质干细胞的衰老。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-08-09 DOI: 10.1111/acel.14293

Qiaojuan Mei, Kexin Li, Tianyu Tang, Siying Cai, Yu Liu, Xiaofei Wang, Yinzhao Jia, Ling Zhang, Huaibiao Li, Hui Song, Jun Zhai, Wenpei Xiang

{"title":"miR-203-3p promotes senescence of mouse bone marrow mesenchymal stem cells via downregulation of Pbk","authors":"Qiaojuan Mei, Kexin Li, Tianyu Tang, Siying Cai, Yu Liu, Xiaofei Wang, Yinzhao Jia, Ling Zhang, Huaibiao Li, Hui Song, Jun Zhai, Wenpei Xiang","doi":"10.1111/acel.14293","DOIUrl":"10.1111/acel.14293","url":null,"abstract":"The senescence of bone marrow mesenchymal stem cells (BMSCs) contributes to the development of degenerative skeletal conditions. To date, the molecular mechanism resulting in BMSC senescence has not been fully understood. In this study, we identified a small non-coding RNA, miR-203-3p, the expression of which was elevated in BMSCs from aged mice. On the other hand, overexpression of miR-203-3p in BMSCs from young mice reduced cell growth and enhanced their senescence. Mechanistically, PDZ-linked kinase (PBK) is predicted to be the target of miR-203-3p. The binding of miR-203-3p to Pbk mRNA could decrease its expression, which in turn inhibited the ubiquitination-mediated degradation of p53. Furthermore, the intravitreal injection of miR-203-3p-inhibitor into the bone marrow cavity of aged mice attenuated BMSC senescence and osteoporosis in aged mice. Collectively, these findings suggest that targeting miR-203-3p to delay BMSC senescence could be a potential therapeutic strategy to alleviate age-related osteoporosis.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 11","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141910894","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

IF 7.8 1区医学

Aging Cell Pub Date : 2024-08-08 DOI: 10.1111/acel.14267

Hansol Lee, Hong-Hsi Lee, Yixin Ma, Laleh Eskandarian, Kyla Gaudet, Qiyuan Tian, Eva A. Krijnen, Andrew W. Russo, David H. Salat, Eric C. Klawiter, Susie Y. Huang

{"title":"Age-related alterations in human cortical microstructure across the lifespan: Insights from high-gradient diffusion MRI","authors":"Hansol Lee, Hong-Hsi Lee, Yixin Ma, Laleh Eskandarian, Kyla Gaudet, Qiyuan Tian, Eva A. Krijnen, Andrew W. Russo, David H. Salat, Eric C. Klawiter, Susie Y. Huang","doi":"10.1111/acel.14267","DOIUrl":"10.1111/acel.14267","url":null,"abstract":"The human brain undergoes age-related microstructural alterations across the lifespan. Soma and Neurite Density Imaging (SANDI), a novel biophysical model of diffusion MRI, provides estimates of cell body (soma) radius and density, and neurite density in gray matter. The goal of this cross-sectional study was to assess the sensitivity of high-gradient diffusion MRI toward age-related alterations in cortical microstructure across the adult lifespan using SANDI. Seventy-two cognitively unimpaired healthy subjects (ages 19–85 years; 40 females) were scanned on the 3T Connectome MRI scanner with a maximum gradient strength of 300mT/m using a multi-shell diffusion MRI protocol incorporating 8 b-values and diffusion time of 19 ms. Intra-soma signal fraction obtained from SANDI model-fitting to the data was strongly correlated with age in all major cortical lobes (r = −0.69 to −0.60, FDR-p < 0.001). Intra-soma signal fraction (r = 0.48–0.63, FDR-p < 0.001) and soma radius (r = 0.28–0.40, FDR-p < 0.04) were significantly correlated with cortical volume in the prefrontal cortex, frontal, parietal, and temporal lobes. The strength of the relationship between SANDI metrics and age was greater than or comparable to the relationship between cortical volume and age across the cortical regions, particularly in the occipital lobe and anterior cingulate gyrus. In contrast to the SANDI metrics, all associations between diffusion tensor imaging (DTI) and diffusion kurtosis imaging metrics and age were low to moderate. These results suggest that high-gradient diffusion MRI may be more sensitive to underlying substrates of neurodegeneration in the aging brain than DTI and traditional macroscopic measures of neurodegeneration such as cortical volume and thickness.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 11","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905184","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

A defective splicing machinery promotes senescence through MDM4 alternative splicing 剪接机制缺陷通过 MDM4 替代剪接促进衰老。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-08-08 DOI: 10.1111/acel.14301

Mathieu Deschênes, Mathieu Durand, Marc-Alexandre Olivier, Alicia Pellerin-Viger, Francis Rodier, Benoit Chabot

{"title":"A defective splicing machinery promotes senescence through MDM4 alternative splicing","authors":"Mathieu Deschênes, Mathieu Durand, Marc-Alexandre Olivier, Alicia Pellerin-Viger, Francis Rodier, Benoit Chabot","doi":"10.1111/acel.14301","DOIUrl":"10.1111/acel.14301","url":null,"abstract":"Defects in the splicing machinery are implicated in various diseases, including cancer. We observed a general reduction in the expression of spliceosome components and splicing regulators in human cell lines undergoing replicative, stress-induced, and telomere uncapping-induced senescence. Supporting the view that defective splicing contributes to senescence, splicing inhibitors herboxidiene, and pladienolide B induced senescence in normal and cancer cell lines. Furthermore, depleting individual spliceosome components also promoted senescence. All senescence types were associated with an alternative splicing transition from the MDM4-FL variant to MDM4-S. The MDM4 splicing shift was reproduced when splicing was inhibited, and spliceosome components were depleted. While decreasing the level of endogenous MDM4 promoted senescence and cell survival independently of the MDM4-S expression status, cell survival was also improved by increasing MDM4-S. Overall, our work establishes that splicing defects modulate the alternative splicing of MDM4 to promote senescence and cell survival.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 11","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905183","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

Are immunosenescent T cells really senescent? 免疫衰老的 T 细胞真的衰老了吗？

IF 7.8 1区医学

Aging Cell Pub Date : 2024-08-07 DOI: 10.1111/acel.14300

Helena Slaets, Naomi Veeningen, Peter L. J. de Keizer, Niels Hellings, Sven Hendrix

{"title":"Are immunosenescent T cells really senescent?","authors":"Helena Slaets, Naomi Veeningen, Peter L. J. de Keizer, Niels Hellings, Sven Hendrix","doi":"10.1111/acel.14300","DOIUrl":"10.1111/acel.14300","url":null,"abstract":"Loss of proper T-cell functioning is a feature of aging that increases the risk of developing chronic diseases. In aged individuals, highly differentiated T cells arise with a reduced expression of CD28 and CD27 and an increased expression of KLRG-1 or CD57. These cells are often referred to as immunosenescent T cells but may still be highly active and contribute to autoimmunity. Another population of T cells known as exhausted T cells arises after chronic antigen stimulation and loses its effector functions, leading to a failure to combat malignancies and viral infections. A process called cellular senescence also increases during aging, and targeting this process has proven to be fruitful against a range of age-related pathologies in animal models. Cellular senescence occurs in cells that are irreparably damaged, limiting their proliferation and typically leading to chronic secretion of pro-inflammatory factors. To develop therapies against pathologies caused by defective T-cell function, it is important to understand the differences and similarities between immunosenescence and cellular senescence. Here, we review the hallmarks of cellular senescence versus senescent and exhausted T cells and provide considerations for the development of specific therapies against age-related diseases.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900209","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

The activation of cGAS-STING pathway causes abnormal uterine receptivity in aged mice cGAS-STING 通路的激活会导致老年小鼠子宫接受能力异常。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-08-07 DOI: 10.1111/acel.14303

Si-Ting Chen, Wen-Wen Shi, Feng Ran, Cheng-Kan Liu, Hui-Na Luo, Li-Juan Wu, Ying Wu, Tong-Tong Zhang, Zeng-Ming Yang

{"title":"The activation of cGAS-STING pathway causes abnormal uterine receptivity in aged mice","authors":"Si-Ting Chen, Wen-Wen Shi, Feng Ran, Cheng-Kan Liu, Hui-Na Luo, Li-Juan Wu, Ying Wu, Tong-Tong Zhang, Zeng-Ming Yang","doi":"10.1111/acel.14303","DOIUrl":"10.1111/acel.14303","url":null,"abstract":"Maternal age is one of the most important factors affecting the success of maternal pregnancy. Uterine aging is the leading cause of pregnancy failure in older women. However, how uterine aging affects uterine receptivity and decidualization is unclear. In this study, naturally aged one-year-old female mice were used to investigate effects of maternal age on embryo implantation during early pregnancy. In our study, we found abnormal uterine receptivity in aged mice. Aged mouse uterus indicates a decrease in nuclear LAMIN A, and an increase in PRELAMIN A and PROGERIN. In aged mouse uterus, double-stranded DNA (dsDNA) in cytoplasmic fraction is significantly increased. PROGERIN overexpression in mouse uterine epithelial cells and epithelial organoids leads to nuclear DNA leakage and impaired uterine receptivity. DNase I, DNase II, and TREX1 are obviously reduced in aged mouse uterus. Treatments with foreign DNA or STING agonist significantly downregulate uterine receptivity markers and activate cGAS-STING pathway. Uterine estrogen (E2) concentration is significantly increased in aged mice. After ovariectomized mice are treated with a high level of E2, there are significant increase of PROGERIN and cytoplasmic DNA, and activation of cGAS-STING pathway. CD14 is significantly increased in aged uterus. Intrauterine CD14 injection inhibits embryo implantation. In vitro CD14 treatment of cultured epithelial cells or epithelial organoids decreases uterine receptivity. Uterine abnormality in aged mouse can be partially rescued by STING inhibitor. In conclusion, uterine PROGERIN increase in aged mouse uterus results in cytoplasmic DNA accumulation and cGAS-STING pathway activation. CD14 secretion in aged uterus impairs uterine receptivity.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 11","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900210","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

Short-term starvation activates AMPK and restores mitochondrial inorganic polyphosphate, but fails to reverse associated neuronal senescence 短期饥饿可激活 AMPK 并恢复线粒体无机多磷酸，但无法逆转相关的神经元衰老。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-08-05 DOI: 10.1111/acel.14289

Luca Tagliafico, Renata T. Da Costa, Lavinia Boccia, Sheida Kavehmoghaddam, Bryan Ramirez, Malgorzata Tokarska-Schlattner, Ernest R. Scoma, Vedangi Hambardikar, Tommaso Bonfiglio, Irene Caffa, Fiammetta Monacelli, Uwe Schlattner, J. Nicholas Betley, Alessio Nencioni, Maria E. Solesio

{"title":"Short-term starvation activates AMPK and restores mitochondrial inorganic polyphosphate, but fails to reverse associated neuronal senescence","authors":"Luca Tagliafico, Renata T. Da Costa, Lavinia Boccia, Sheida Kavehmoghaddam, Bryan Ramirez, Malgorzata Tokarska-Schlattner, Ernest R. Scoma, Vedangi Hambardikar, Tommaso Bonfiglio, Irene Caffa, Fiammetta Monacelli, Uwe Schlattner, J. Nicholas Betley, Alessio Nencioni, Maria E. Solesio","doi":"10.1111/acel.14289","DOIUrl":"10.1111/acel.14289","url":null,"abstract":"Neuronal senescence is a major risk factor for the development of many neurodegenerative disorders. The mechanisms that drive neurons to senescence remain largely elusive; however, dysregulated mitochondrial physiology seems to play a pivotal role in this process. Consequently, strategies aimed to preserve mitochondrial function may hold promise in mitigating neuronal senescence. For example, dietary restriction has shown to reduce senescence, via a mechanism that still remains far from being totally understood, but that could be at least partially mediated by mitochondria. Here, we address the role of mitochondrial inorganic polyphosphate (polyP) in the intersection between neuronal senescence and dietary restriction. PolyP is highly present in mammalian mitochondria; and its regulatory role in mammalian bioenergetics has already been described by us and others. Our data demonstrate that depletion of mitochondrial polyP exacerbates neuronal senescence, independently of whether dietary restriction is present. However, dietary restriction in polyP-depleted cells activates AMPK, and it restores some components of mitochondrial physiology, even if this is not sufficient to revert increased senescence. The effects of dietary restriction on polyP levels and AMPK activation are conserved in differentiated SH-SY5Y cells and brain tissue of male mice. Our results identify polyP as an important component in mitochondrial physiology at the intersection of dietary restriction and senescence, and they highlight the importance of the organelle in this intersection.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 11","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892394","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

Senescence detection using reflected light 利用反射光进行衰老检测

IF 7.8 1区医学

Aging Cell Pub Date : 2024-08-05 DOI: 10.1111/acel.14295

Benjamin Dedic, Leo Westerberg, Andrea Mosqueda Solís, Kyle D. Dumont, Jorge L. Ruas, Anders Thorell, Erik Näslund, Kirsty L. Spalding

{"title":"Senescence detection using reflected light","authors":"Benjamin Dedic, Leo Westerberg, Andrea Mosqueda Solís, Kyle D. Dumont, Jorge L. Ruas, Anders Thorell, Erik Näslund, Kirsty L. Spalding","doi":"10.1111/acel.14295","DOIUrl":"10.1111/acel.14295","url":null,"abstract":"Senescence is an important cellular program occurring in development, tissue repair, cancer, and aging. Increased senescence is also associated with disease states, including obesity and Type 2 diabetes (T2D). Characterizing and quantifying senescent cells at a single cell level has been challenging and particularly difficult in large primary cells, such as human adipocytes. In this study, we present a novel approach that utilizes reflected light for accurate senescence-associated beta-galactosidase (SABG) staining measurements, which can be integrated with immunofluorescence and is compatible with primary mature adipocytes from both human and mouse, as well as with differentiated 3T3-L1 cells. This technique provides a more comprehensive classification of a cell's senescent state by incorporating multiple criteria, including robust sample-specific pH controls. By leveraging the precision of confocal microscopy to detect X-gal crystals using reflected light, we achieved superior sensitivity over traditional brightfield techniques. This strategy allows for the capture of all X-gal precipitates in SABG-stained samples, revealing diverse X-gal staining patterns and improved detection sensitivity. Additionally, we demonstrate that reflected light outperforms western blot analysis for the detection and quantification of senescence in mature human adipocytes, as it offers a more accurate representation of SABG activity. This detection strategy enables a more thorough investigation of senescent cell characteristics and specifically a deeper look at the relationship between adipocyte senescence and obesity associated disorders, such as T2D.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 11","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892393","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