Mechanisms of Ageing and Development最新文献_第6页

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}

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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}

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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

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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}

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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}

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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

Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration 实现个性化的烟酰胺单核苷酸（NMN）补充：烟酰胺腺嘌呤二核苷酸（NAD）浓度

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-02-29 DOI: 10.1016/j.mad.2024.111917

Ajla Hodzic Kuerec , Weilan Wang , Lin Yi , Rongsheng Tao , Zhigang Lin , Aditi Vaidya , Sohal Pendse , Sornaraja Thasma , Niranjan Andhalkar , Ganesh Avhad , Vidyadhar Kumbhar , Andrea B. Maier

{"title":"Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration","authors":"Ajla Hodzic Kuerec , Weilan Wang , Lin Yi , Rongsheng Tao , Zhigang Lin , Aditi Vaidya , Sohal Pendse , Sornaraja Thasma , Niranjan Andhalkar , Ganesh Avhad , Vidyadhar Kumbhar , Andrea B. Maier","doi":"10.1016/j.mad.2024.111917","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111917","url":null,"abstract":"<div><p>Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which declines with age. Supplementation of NMN has been shown to improve blood NAD concentration. However, the optimal NMN dose remains unclear. This is a post-hoc analysis of a double-blinded clinical trial involving 80 generally healthy adults aged 40–65 years. The participants received a placebo or daily 300 mg, 600 mg, or 900 mg NMN for 60 days. Blood NAD concentration, blood biological age, homeostatic model assessment for insulin resistance, 6-minute walk test, and 36-item short-form survey (SF-36) were measured at baseline and after supplement. A significant dose-dependent increase in NAD concentration change (NAD<sub>Δ</sub>) was observed following NMN supplementation, with a large coefficient of variation (29.2–113.3%) within group. The increase in NAD<sub>Δ</sub> was associated with an improvement in the walking distance of 6-minute walk test and the SF-36 score. The median effect dose of NAD<sub>Δ</sub> for the 6-minute walk test and SF-36 score was 15.7 nmol/L (95% CI: 10.9–20.5 nmol/L) and 13.5 nmol/L (95% CI; 10.5–16.5 nmol/L), respectively. Because of the high interindividual variability of the NAD<sub>Δ</sub> after NMN supplementation, monitoring NAD concentration can provide valuable insights for tailoring personalized dosage regimens and optimizing NMN utilization.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111917"},"PeriodicalIF":5.3,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000174/pdfft?md5=596090ef08c0556c0ae9813c959d2a65&pid=1-s2.0-S0047637424000174-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140016076","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

Insights into targeting cellular senescence with senolytic therapy: The journey from preclinical trials to clinical practice 以细胞衰老为靶点的衰老疗法：从临床前试验到临床实践的历程。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-02-23 DOI: 10.1016/j.mad.2024.111918

Peng Chen , Yulai Wang , Benhong Zhou

引用次数: 0