Mechanisms of Ageing and Development最新文献_第8页

Effect of in vivo culture conditions on the proliferation and differentiation of rat adipose-derived stromal cells 体内培养条件对大鼠脂肪基质细胞增殖和分化的影响

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-04-12 DOI: 10.1016/j.mad.2024.111935

Chao Wang , Tian Xie , Xiaoming Li , Xue Lu , Changxue Xiao , Ping Liu , Feng Xu , Bo Zhang

{"title":"Effect of in vivo culture conditions on the proliferation and differentiation of rat adipose-derived stromal cells","authors":"Chao Wang , Tian Xie , Xiaoming Li , Xue Lu , Changxue Xiao , Ping Liu , Feng Xu , Bo Zhang","doi":"10.1016/j.mad.2024.111935","DOIUrl":"10.1016/j.mad.2024.111935","url":null,"abstract":"<div><p>Adipose-derived stromal cells (ADSCs) are promising stem cell sources for tissue engineering and cell-based therapy. However, long-term <em>in vitro</em> expansion of ADSCs impedes stemness maintenance, which is partly attributed to deprivation of their original microenvironment. Incompetent cells limit the therapeutic effects of ADSC-based clinical strategies. Therefore, reconstructing a more physiologically and physically relevant niche is an ideal strategy to address this issue and therefore facilitates the extensive application of ADSCs. Here, we transplanted separated ADSCs into local subcutaneous adipose tissues of nude mice as an <em>in vivo</em> cell culture model. We found that transplanted ADSCs maintained their primitive morphology and showed improved proliferation and delayed senescence compared to those of cells cultured in an incubator. Significantly increased expression of stemness-related markers and multilineage differentiation abilities were further observed in <em>in vivo</em> cultured ADSCs. Finally, sequencing revealed that genes whose expression differed between ADSCs obtained under <em>in vivo</em> and <em>in vitro</em> conditions were mainly located in the extracellular matrix and extracellular space and that these genes participate in regulating transcription and protein synthesis. Moreover, we found that an Egr1 signaling pathway might exert a crucial impact on controlling stemness properties. Our findings might collectively pave the way for ADSC-based applications.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111935"},"PeriodicalIF":5.3,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140761275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasma cfDNA abundance as a prognostic biomarker for higher risk of death in geriatric cardiovascular patients 血浆 cfDNA 丰度是老年心血管病人死亡风险较高的预后生物标志物

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-04-09 DOI: 10.1016/j.mad.2024.111934

Maurizio Cardelli , Francesca Marchegiani , Pierpaolo Stripoli , Francesco Piacenza , Rina Recchioni , Mirko Di Rosa , Robertina Giacconi , Marco Malavolta , Roberta Galeazzi , Beatrice Arosio , Fiammetta Cafarelli , Francesco Spannella , Antonio Cherubini , Fabrizia Lattanzio , Fabiola Olivieri

{"title":"Plasma cfDNA abundance as a prognostic biomarker for higher risk of death in geriatric cardiovascular patients","authors":"Maurizio Cardelli , Francesca Marchegiani , Pierpaolo Stripoli , Francesco Piacenza , Rina Recchioni , Mirko Di Rosa , Robertina Giacconi , Marco Malavolta , Roberta Galeazzi , Beatrice Arosio , Fiammetta Cafarelli , Francesco Spannella , Antonio Cherubini , Fabrizia Lattanzio , Fabiola Olivieri","doi":"10.1016/j.mad.2024.111934","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111934","url":null,"abstract":"<div><p>The management of geriatric cardiovascular disease (CVD) patients with multimorbidity remains challenging and could potentially be improved by integrating clinical data with innovative prognostic biomarkers. In this context, the analysis of circulating analytes, including cell-free DNA (cfDNA), appears particularly promising. Here, we investigated circulating cfDNA (measured through the quantification of 247 bp and 115 bp Alu genomic fragments) in a cohort of 244 geriatric CVD patients with multimorbidity hospitalised for acute CVD or non-CVD events. Survival analysis showed a direct association between Alu 247 cfDNA abundance and risk of death, particularly evident in the first six months after admission for acute CVD events. Higher plasma cfDNA concentration was associated with mortality in the same period of time. The cfDNA integrity (Alu 247/115), although not associated with outcome, appeared to be useful in discriminating patients in whom Alu 247 cfDNA abundance is most effective as a prognostic biomarker. The cfDNA parameters were associated with several biochemical markers of inflammation and myocardial damage. In conclusion, an increase in plasma cfDNA abundance at hospital admission is indicative of a higher risk of death in geriatric CVD patients, especially after acute CVD events, and its analysis may be potentially useful for risk stratification.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111934"},"PeriodicalIF":5.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of Seipin in cholesterol mediated lipid droplet maturation; status of endoplasmic reticulum stress and lipophagy Seipin 在胆固醇介导的脂滴成熟过程中的影响；内质网应激和噬脂作用的现状

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-04-07 DOI: 10.1016/j.mad.2024.111933

Tugce Demirel-Yalciner , Bengu Cetinkaya , Erdi Sozen , Nesrin Kartal Ozer

{"title":"Impact of Seipin in cholesterol mediated lipid droplet maturation; status of endoplasmic reticulum stress and lipophagy","authors":"Tugce Demirel-Yalciner , Bengu Cetinkaya , Erdi Sozen , Nesrin Kartal Ozer","doi":"10.1016/j.mad.2024.111933","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111933","url":null,"abstract":"<div><p>The global prevalence of nonalcoholic fatty liver disease (NAFLD) defined by the increased number of lipid droplets (LDs) in hepatocytes, have risen continuously in parallel with the obesity. LDs and related proteins are known to affect cellular metabolism and signaling. Seipin, one of the most important LD-related proteins, plays a critical role in LD biogenesis. Although the role of adipose tissue-specific Seipin silencing is known, hepatocyte-specific silencing upon cholesterol-mediated lipid accumulation has not been investigated. In our study, we investigated the effect of Seipin on endoplasmic reticulum (ER) stress and lipophagy in cholesterol accumulated mouse hepatocyte cells. In this direction, cholesterol accumulation was induced by cholesterol-containing liposome, while Seipin mRNA and protein levels were reduced by siRNA. Our findings show that cholesterol containing liposome administration in hepatocytes increases both Seipin protein and number of large LDs. However Seipin silencing reduced the increase of cholesterol mediated large LDs and Glucose-regulated protein 78 (GRP78) mRNA. Additionally, lysosome-LD colocalization increased only in cells treated with cholesterol containing liposome, while the siRNA against Seipin did not lead any significant difference. According to our findings, we hypothesize that Seipin silencing in hepatocytes reduced cholesterol mediated LD maturation as well as GRP78 levels, but not lipophagy.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111933"},"PeriodicalIF":5.3,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Renal lipid accumulation and aging linked to tubular cells injury via ANGPTL4 肾脏脂质积累和衰老与肾小管细胞通过 ANGPTL4 受损有关

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-04-03 DOI: 10.1016/j.mad.2024.111932

Xiaojun Wang , Hung-chen Chang , Xuchao Gu , Wanlin Han , Shihang Mao , Lili Lu , Shuai Jiang , Haiyong Ding , Shisheng Han , Xinkai Qu , Zhijun Bao

{"title":"Renal lipid accumulation and aging linked to tubular cells injury via ANGPTL4","authors":"Xiaojun Wang , Hung-chen Chang , Xuchao Gu , Wanlin Han , Shihang Mao , Lili Lu , Shuai Jiang , Haiyong Ding , Shisheng Han , Xinkai Qu , Zhijun Bao","doi":"10.1016/j.mad.2024.111932","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111932","url":null,"abstract":"<div><p>Renal tubular epithelial cells are vulnerable to stress-induced damage, including excessive lipid accumulation and aging, with ANGPTL4 potentially playing a crucial bridging role between these factors. In this study, RNA-sequencing was used to identify a marked increase in ANGPTL4 expression in kidneys of diet-induced obese and aging mice. Overexpression and knockout of ANGPTL4 in renal tubular epithelial cells (HK-2) was used to investigate the underlying mechanism. Subsequently, ANGPTL4 expression in plasma and kidney tissues of normal young controls and elderly individuals was analyzed using ELISA and immunohistochemical techniques. RNA sequencing results showed that ANGPTL4 expression was significantly upregulated in the kidney tissue of diet-induced obesity and aging mice. In vitro experiments demonstrated that overexpression of ANGPTL4 in HK-2 cells led to increased lipid deposition and senescence. Conversely, the absence of ANGPTL4 appears to alleviate the impact of free fatty acids (FFA) on aging in HK-2 cells. Additionally, aging HK-2 cells exhibited elevated ANGPTL4 expression, and stress response markers associated with cell cycle arrest. Furthermore, our clinical evidence revealed dysregulation of ANGPTL4 expression in serum and kidney tissue samples obtained from elderly individuals compared to young subjects. Our study findings indicate a potential association between ANGPTL4 and age-related metabolic disorders, as well as injury to renal tubular epithelial cells. This suggests that targeting ANGPTL4 could be a viable strategy for the clinical treatment of renal aging.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111932"},"PeriodicalIF":5.3,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In the land of not-unhappiness: On the state-of-the-art of targeting aging and age-related diseases by biomedical research 在不幸福的国度：生物医学研究针对老龄化和老年相关疾病的最新进展。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-03-30 DOI: 10.1016/j.mad.2024.111929

Eirini Klinaki , Mikolaj Ogrodnik

引用次数: 0

Molecular mechanisms implicated in protein changes in the Alzheimer’s disease human hippocampus 阿尔茨海默氏症人类海马蛋白质变化的分子机制。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-03-28 DOI: 10.1016/j.mad.2024.111930

Hai Duc Nguyen , Woong-Ki Kim , Huong Huong Vu

{"title":"Molecular mechanisms implicated in protein changes in the Alzheimer’s disease human hippocampus","authors":"Hai Duc Nguyen , Woong-Ki Kim , Huong Huong Vu","doi":"10.1016/j.mad.2024.111930","DOIUrl":"10.1016/j.mad.2024.111930","url":null,"abstract":"<div><p>This study aimed to elucidate the specific biochemical pathways linked to changes in proteins in the Alzheimer's disease (AD) human hippocampus. Our data demonstrate a constant rise in the expression of four proteins (VGF, GFAP, HSPB1, and APP) across all eleven studies. Notably, UBC was the most centrally involved and had increased expression in the hippocampus tissue of individuals with AD. Modified proteins in the hippocampal tissue were found to activate the innate immune system and disrupt communication across chemical synapses. Four hub proteins (CD44, APP, ITGB2, and APOE) are connected to amyloid plaques, whereas two hub proteins (RPL24 and RPS23) are related to neurofibrillary tangles (NFTs). The presence of modified proteins was discovered to trigger the activation of microglia and decrease the functioning of ribosomes and mitochondria in the hippocampus. Three significant microRNAs (hsa-miR-106b-5p, hsa-miR-17–5p, and hsa-miR-16–5p) and transcription factors (MYT1L, PIN1, and CSRNP3) have been discovered to improve our understanding of the alterations in proteins within the hippocampal tissues that lead to the progression of AD. These findings establish a path for possible treatments for AD to employ therapeutic strategies that specifically focus on the proteins or processes linked to the illness.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111930"},"PeriodicalIF":5.3,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000307/pdfft?md5=ef967dca271792cddf413546b3910dd8&pid=1-s2.0-S0047637424000307-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Mitochondria-targeted esculetin and metformin delay endothelial senescence by promoting fatty acid β-oxidation: Relevance in age-associated atherosclerosis 以线粒体为靶点的埃斯库莱汀和二甲双胍通过促进脂肪酸β-氧化来延缓内皮细胞衰老：与年龄相关性动脉粥样硬化的关系

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-03-28 DOI: 10.1016/j.mad.2024.111931

Sriravali Pulipaka , Hridya Chempon , Gajalakshmi Singuru , Shashikanta Sahoo , Altab Shaikh , Sunita Kumari , Rajamannar Thennati , Srigiridhar Kotamraju

{"title":"Mitochondria-targeted esculetin and metformin delay endothelial senescence by promoting fatty acid β-oxidation: Relevance in age-associated atherosclerosis","authors":"Sriravali Pulipaka , Hridya Chempon , Gajalakshmi Singuru , Shashikanta Sahoo , Altab Shaikh , Sunita Kumari , Rajamannar Thennati , Srigiridhar Kotamraju","doi":"10.1016/j.mad.2024.111931","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111931","url":null,"abstract":"<div><p>Impaired mitochondrial fatty acid β<strong>-</strong>oxidation (FAO) plays a role in the onset of several age-associated diseases, including atherosclerosis. In the current work, we investigated the efficacies of mitochondria-targeted esculetin (Mito-Esc) and metformin in enhancing FAO in human aortic endothelial cells (HAECs), and its relevance in the delay of cellular senescence and age-associated atherosclerotic plaque formation in <em>Apoe</em><sup>-/-</sup> mice. Chronic culturing of HAECs with either Mito-Esc or metformin increased oxygen consumption rates (OCR), and caused delay in senescence features. Conversely, etomoxir (CPT1 inhibitor) reversed Mito-Esc- and metformin-induced OCR, and caused premature endothelial senescence. Interestingly, Mito-Esc, unlike metformin, in the presence of etomoxir failed to preserve OCR. Thereby, underscoring Mito-Esc’s exclusive reliance on FAO as an energy source. Mechanistically, chronic culturing of HAECs with either Mito-Esc or metformin led to AMPK activation, increased CPT1 activity, and acetyl-CoA levels along with a concomitant reduction in malonyl-CoA levels, and lipid accumulation. Similar results were observed in Apoe<sup>-/-</sup> mice aorta and liver tissue with a parallel reduction in age-associated atherosclerotic plaque formation and degeneration of liver with either Mito-Esc or metformin administration. Together, Mito-Esc and metformin by potentiating FAO, may have a role in the delay of cellular senescence by modulating mitochondrial function.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111931"},"PeriodicalIF":5.3,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unraveling the dual role of ADAM10: Bridging the gap between cancer and Alzheimer’s disease 揭示 ADAM10 的双重作用：弥合癌症与阿尔茨海默病之间的鸿沟。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-03-19 DOI: 10.1016/j.mad.2024.111928

Vanessa Alexandre-Silva, Marcia Regina Cominetti

{"title":"Unraveling the dual role of ADAM10: Bridging the gap between cancer and Alzheimer’s disease","authors":"Vanessa Alexandre-Silva, Marcia Regina Cominetti","doi":"10.1016/j.mad.2024.111928","DOIUrl":"10.1016/j.mad.2024.111928","url":null,"abstract":"<div><p>An inverse association between Alzheimer’s disease (AD) and cancer has been proposed. Patients with a cancer history have a decreased risk of developing AD, and AD patients have a reduced cancer incidence, which is not seen in vascular dementia patients. Given this association, common molecular and biological mechanisms that could explain this inverse relationship have been proposed before, such as Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (Pin1), Wingless and Int-1 (Wnt), and transformation-related protein 53 (p53)-mediated pathways, along with inflammation and oxidative stress-related proteins. A Disintegrin And Metalloprotease 10 (ADAM10) is a protease responsible for the cleavage of key AD- and cancer-related substrates, and it has inverse roles in those diseases: neuroprotective and disease-promoting, respectively. Thus, herein, we review the relevant literature linking AD and cancer and propose how ADAM10 activity might modulate the inverse association between the diseases. Understanding how this protease mediates those two conditions might raise some considerations in the ADAM10 pharmacological modulation for treating AD and cancer.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111928"},"PeriodicalIF":5.3,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of the demographic history on the evolution of senescence: A potential new test of the mutation accumulation theory 人口历史对衰老进化的影响：对突变累积理论的潜在新检验。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-03-16 DOI: 10.1016/j.mad.2024.111927

Guillaume Péron

{"title":"The effect of the demographic history on the evolution of senescence: A potential new test of the mutation accumulation theory","authors":"Guillaume Péron","doi":"10.1016/j.mad.2024.111927","DOIUrl":"10.1016/j.mad.2024.111927","url":null,"abstract":"<div><p>The different evolutionary theories of senescence predict different directions for the correlation between the population size and the intensity of senescence. Using simulations, I highlighted how the effect of the population size on the intensity of senescence could be reinforced by the time since populations have been large or small. I devised a mutation-selection model in which the effect of the mutations was age-specific. Several small populations diverged from a same large population at different points in time. At the end of the simulation, the correlation between the time since the populations had been small and the rate of senescence was positive under the mutation accumulation theory and negative under the antagonistic pleiotropy theory. The phenomenon was strong enough to reverse the usually negative relationship between the intensity of senescence and the generation time. These mutually-exclusive predictions could help broaden the taxonomic support for the mutation accumulation theory of senescence, currently mostly supported in humans and lab invertebrates. I briefly mention a few potential applications in real-life systems.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111927"},"PeriodicalIF":5.3,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of longevity-related genetic variant interactions as predictors of survival after 85 years of age 与长寿相关的遗传变异相互作用对 85 岁后存活率的预测作用。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-03-13 DOI: 10.1016/j.mad.2024.111926

Maja Šetinc , Željka Celinšćak , Luka Bočkor , Matea Zajc Petranović , Anita Stojanović Marković , Marijana Peričić Salihović , Joris Deelen , Tatjana Škarić-Jurić

{"title":"The role of longevity-related genetic variant interactions as predictors of survival after 85 years of age","authors":"Maja Šetinc , Željka Celinšćak , Luka Bočkor , Matea Zajc Petranović , Anita Stojanović Marković , Marijana Peričić Salihović , Joris Deelen , Tatjana Škarić-Jurić","doi":"10.1016/j.mad.2024.111926","DOIUrl":"10.1016/j.mad.2024.111926","url":null,"abstract":"<div><p>Genome-wide association studies and candidate gene studies have identified several genetic variants that might play a role in achieving longevity. This study investigates interactions between pairs of those single nucleotide polymorphisms (SNPs) and their effect on survival above the age of 85 in a sample of 327 Croatian individuals. Although none of the SNPs individually showed a significant effect on survival in this sample, 14 of the 359 interactions tested (between SNPs not in LD) reached the level of nominal significance (p<0.05), showing a potential effect on late-life survival. Notably, <em>SH2B3</em> rs3184504 interacted with different SNPs near <em>TERC</em>, <em>TP53</em> rs1042522 with different SNPs located near the <em>CDKN2B</em> gene, and <em>CDKN2B</em> rs1333049 with different SNPs in <em>FOXO3</em>, as well as with <em>LINC02227</em> rs2149954. The other interaction pairs with a possible effect on survival were <em>FOXO3</em> rs2802292 and <em>ERCC2</em> rs50871, <em>IL6</em> rs1800795 and <em>GHRHR</em> rs2267723, <em>LINC02227</em> rs2149954 and <em>PARK7</em> rs225119, as well as <em>PARK7</em> rs225119 and <em>PTPN1</em> rs6067484. These interactions remained significant when tested together with a set of health-related variables that also had a significant effect on survival above 85 years. In conclusion, our results confirm the central role of genetic regulation of insulin signalling and cell cycle control in longevity.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111926"},"PeriodicalIF":5.3,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000265/pdfft?md5=9104fa7f88299f2be2e88baf6a5738fd&pid=1-s2.0-S0047637424000265-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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