Experimental gerontology最新文献

{"title":"The causal relationship of inflammation-related factors with osteoporosis: A Mendelian Randomization Analysis","authors":"Xinyue Yang ,&nbsp;Rui Xiao ,&nbsp;Beizhong Liu ,&nbsp;Bo Xie ,&nbsp;Zhao Yang","doi":"10.1016/j.exger.2025.112715","DOIUrl":"10.1016/j.exger.2025.112715","url":null,"abstract":"<div><h3>Background</h3><div>We used Mendelian randomization (MR) approach to examine whether genetically determined inflammation-related risk factors play a role in the onset of osteoporosis (OP) in the European population.</div></div><div><h3>Methods</h3><div>Genome-wide association studies (GWASs) summary statistics of estimated bone mineral density (eBMD) obtained from the public database GEnetic Factors for OSteoporosis Consortium (GEFOS) including 142,487 European people. For exposures, we utilized GWAS data of 9 risk factors including diseases chronic kidney disease (CKD) (41,395 cases and 439,303 controls), type 2 diabetes (T2D) (88,427 cases and 566,778 controls), Alzheimer's disease (AD) (71,880 cases, 383,378 controls) and major depression disorder (MDD) (9240 cases and 9519 controls) and lifestyle behaviors are from different consortiums. Inverse variance weighted (IVW) analysis was principal method in this study and random effect model was applied; MR-Egger method and weighted median method were also performed for reliable results. Cochran's Q test and MR-Egger regression were used to detect heterogeneity and pleiotropy and leave-one-out analysis was performed to find out whether there are influential SNPs.</div></div><div><h3>Results</h3><div>We found that T2D (<em>IVW: β =</em> <em>0.05, P</em> <em>=</em> <em>0.0014</em>), FI (<em>IVW: β = −0.22, P</em> <em>&lt;</em> <em>0.001</em>), CKD (<em>IVW: β =</em> <em>0.02, P</em> <em>=</em> <em>0.009</em>), ALZ (<em>IVW: β =</em> <em>0.06, P</em> <em>=</em> <em>0.005</em>), Coffee consumption (<em>IVW: β = 0.11, P</em> <em>=</em> <em>0.003</em>) were causally associated with OP (<span><math><mi>P</mi><mo>&lt;</mo><mn>0.006</mn><mspace></mspace></math></span>after Bonferroni correction).</div></div><div><h3>Conclusions</h3><div>Our study revealed that T2D, FI, CKD, ALZ and coffee consumption are causally associated with OP. Future interventions targeting factors above could provide new clinical strategies for the personalized prevention and treatment of osteoporosis.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"202 ","pages":"Article 112715"},"PeriodicalIF":3.9,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular senescence and glaucoma","authors":"Liang Guo ,&nbsp;Na Wang ,&nbsp;Jing Chen ,&nbsp;Rui Zhang ,&nbsp;Dan Li ,&nbsp;Lu Yang","doi":"10.1016/j.exger.2025.112718","DOIUrl":"10.1016/j.exger.2025.112718","url":null,"abstract":"<div><div>Cellular senescence, a characteristic feature of the aging process, is induced by diverse stressors. In recent years, glaucoma has emerged as a blinding ocular disease intricately linked to cellular senescence. The principal pathways implicated are oxidative stress, mitochondrial dysfunction, DNA damage, autophagy impairment, and the secretion of various senescence- associated secretory phenotype factors. Research on glaucoma-associated cellular senescence predominantly centers around the increased resistance of the aqueous humor outflow pathway, which is attributed to the senescence of the trabecular meshwork and Schlemm's canal. Additionally, it focuses on the mechanisms underlying retinal ganglion cell senescence in glaucoma and the corresponding intervention measures. Given that cell senescence represents an irreversible phase preceding cell death, an in-depth investigation into its mechanisms in the pathogenesis and progression of glaucoma, particularly by specifically blocking the signal transduction of cell senescence, holds the potential to decrease the outflow resistance of aqueous humor. This, in turn, could provide a novel avenue for safeguarding the optic nerve in glaucoma.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"202 ","pages":"Article 112718"},"PeriodicalIF":3.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of 15-PGDH by SW033291 ameliorates age-related heart failure in mice","authors":"Li Zhang ,&nbsp;Qiang Wang ,&nbsp;Wenjun Guan","doi":"10.1016/j.exger.2025.112710","DOIUrl":"10.1016/j.exger.2025.112710","url":null,"abstract":"<div><div>Chronic loss of cardiomyocyte integrity underlies human heart failure associated with aging that often involves progression of acute myocardial infarction and the maladaptive response of cardiomyopathy. SW033291, an inhibitor of 15-prostaglandin dehydrogenase (15-PGDH), has been shown to mitigate fibrosis of mice heart. Whether it has cardioprotective effect remain unknown. Young and aged C57BL/6 J mice were treated with either the vehicle or SW033291 for four weeks. The expression of the target gene was assessed by RT-qPCR, Western blotting, and ELISA. Cardiac function was measured by echocardiography. Our study demonstrated that SW033291 induced a notable upregulation of prostaglandin E2 while concurrently downregulated the expression of both 15-PGDH and troponin I in cardiac tissues, encompassing both young and aged mice. Notably, the administration of SW033291 resulted in a significant improvement in systolic and diastolic function among aged mice, although this effect was not observed in their younger counterparts. Subsequent investigations focusing on exploring the mechanisms, revealed that repetitive administration of SW033291 effectively mitigated age-induced oxidative stress and curtailed chronic inflammation within the cardiac tissues of aged mice. These pivotal findings establish a solid foundation for contemplating the prospective therapeutic application of SW033291 in addressing age-related heart failure.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"202 ","pages":"Article 112710"},"PeriodicalIF":3.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biology of sex differences in frailty and aging: Where are we?","authors":"Beatrice Arosio, Emanuele Marzetti, Anna Picca","doi":"10.1016/j.exger.2025.112711","DOIUrl":"10.1016/j.exger.2025.112711","url":null,"abstract":"","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":" ","pages":"112711"},"PeriodicalIF":3.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statin is associated with higher cortical thickness in early Alzheimer's disease","authors":"Yane Zheng ,&nbsp;Huiying Gu ,&nbsp;Yuming Kong ,&nbsp;Alzheimer's Disease Neuroimaging Initiative (ADNI)","doi":"10.1016/j.exger.2025.112698","DOIUrl":"10.1016/j.exger.2025.112698","url":null,"abstract":"<div><h3>Background</h3><div>The brain is the most cholesterol-rich organ, essential for myelination and neuronal function. Statins, widely used to lower cholesterol, cross the blood-brain barrier and may impact brain cholesterol synthesis. Despite their widespread use, the effects of statins on cortical regions relevant to Alzheimer's disease (AD) are not well understood. This study aimed to compare cortical thickness between statin-exposed and statin-unexposed older adults and evaluate the potential neuroprotective effects of statins.</div></div><div><h3>Methods</h3><div>Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The sample included 193 healthy controls (HC), 485 individuals with mild cognitive impairment (MCI), and 169 individuals with Alzheimer's disease (AD). Participants were categorized as statin users if they had used statins for at least two years. MRI data were processed using FreeSurfer software to estimate cortical thickness in 64 regions of interest. ANCOVA models assessed the association between statin use and cortical thickness at baseline, and linear mixed models evaluated longitudinal changes.</div></div><div><h3>Results</h3><div>Statin use was associated with increased cortical thickness in multiple brain regions across HC, MCI, and AD participants. In HC, statin users had greater thickness in the right lateral occipital, left middle temporal, and left parahippocampal regions. MCI participants exhibited additional increases in the right cuneus, right posterior cingulate, and left superior temporal cortex. In AD, statin users had higher thickness in the right cuneus and right superior parietal lobule. Longitudinal analysis revealed no statin-related differences in cortical thickness changes among HC and AD groups, but in MCI, statins slowed cortical thinning in the left medial orbitofrontal cortex.</div></div><div><h3>Conclusion</h3><div>Statin use is associated with greater cortical thickness in older adults, particularly in those with MCI. These findings suggest that statins may have neuroprotective effects, potentially mitigating neurodegenerative changes in early cognitive decline. Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and understand the mechanisms involved.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"202 ","pages":"Article 112698"},"PeriodicalIF":3.9,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between urinary trace elements levels and depressive symptoms among the older population","authors":"Ying Zhang ,&nbsp;Junjiao Ping ,&nbsp;Dong Cui ,&nbsp;Zhenkun Tan ,&nbsp;Jiali Luo ,&nbsp;Chuijia Kong ,&nbsp;Na Xiao ,&nbsp;Haiyan Lv ,&nbsp;Xinxia Liu","doi":"10.1016/j.exger.2025.112709","DOIUrl":"10.1016/j.exger.2025.112709","url":null,"abstract":"<div><h3>Background</h3><div>Late-life depression is a prevalent public health issue among the elderly. Imbalances in trace elements are increasingly recognized as associated with depression; however, the majority of current research has concentrated on examining the link between blood-based trace elements levels and depressive symptoms. Our objective was to determine if a similar correlation is observed between urinary trace elements levels and depressive symptoms.</div></div><div><h3>Methods</h3><div>We employed stratified, multi-stage random sampling to recruit 400 participants, aged 60 years or older, from a community-based population in a city located in southern China. The Patient Health Questionnaire-9 Items (PHQ-9) was utilized to evaluate depressive symptoms. The concentration of trace elements in urine was detected by inductively coupled plasma mass spectrometry. Multiple logistic regression analysis was conducted to assess the association between urinary trace elements levels and depressive symptoms, as well as the interactions between these levels and potential covariates. The Restricted Cubic Spline (RCS) model with four knots to further explore the association between urinary trace elements and depressive symptoms risk after adjusting for the confounders.</div></div><div><h3>Results</h3><div>A total of 391 participants were investigated, including 50 (12.6 %) in depressive symptom group and 341 (87.4 %) in non-depressive symptom group. Urinary copper levels were positively correlated with depressive symptoms. Compared with the lowest tertile of urinary copper, the multivariate adjusted odds ratios of depressive symptom were 2.58 (1.18–5.64) in tertile 3. Furthermore, we found the interactions between urinary copper and gender were <em>p</em> &lt; 0.05. The multivariate correction OR for T3 versus T1 in males was 21.10 (1.79–248.13) (<em>P</em>_{for trend} = 0.002). RCS analysis revealed a positive association between copper levels and depressive symptoms (<em>P</em>-overall association = 0.025, and <em>P</em>-nonlinear = 0.161). No significant difference was observed in the risk of developing depressive symptoms among individuals with urinary copper concentrations below 8.22 μg/g creatinine. However, the risk of depressive symptoms increases progressively as the urinary copper concentration exceeds this threshold.</div></div><div><h3>Conclusion</h3><div>Urinary copper levels are correlated with the development of depressive symptoms, and copper exposure in men is more sensitive to depressive symptoms. Urinary copper, as a non-invasive test, is a promising indicator of depression symptoms in environmental exposure.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"202 ","pages":"Article 112709"},"PeriodicalIF":3.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-fibrosis effect and its mechanism of atractylenolide III on post-traumatic extending knee joint contracture in rats","authors":"Bin-Bin Zhang ,&nbsp;Lei Xu ,&nbsp;Quan-Bing Zhang ,&nbsp;Yan Wang ,&nbsp;Chen Chen ,&nbsp;Jin-Niu Zhang ,&nbsp;Xian-Liang Rao ,&nbsp;Bing-Jing Zhu ,&nbsp;Xue-Ming Li ,&nbsp;De-Ting Zhu ,&nbsp;Xiu-Li Kan ,&nbsp;Jing Mao ,&nbsp;Run Zhang ,&nbsp;Yun Zhou","doi":"10.1016/j.exger.2025.112708","DOIUrl":"10.1016/j.exger.2025.112708","url":null,"abstract":"<div><h3>Objectives</h3><div>Atractylenolide III (ATL III) is the major bioactive component found in Atractylodes macrocephala, which has shown a range of benefits in pharmacological studies, including neuroprotection, anti-neuroinflammatory properties, antioxidant effects, anti-allergic effects, anti-cancer properties and antifibrotic abilities. Here, we investigated the therapeutic potential and underlying mechanisms of ATL III in the treatment of post-traumatic joint contracture (PTJC) in rat knees.</div></div><div><h3>Methods</h3><div>The rat PTJC model and TGF-β1-induced a primary synovial fibroblast model were used to observe several fibrotic markers (α-SMA、TGF-β1、FGF2、COL1A1and COL3A1) using histological staining, immunofluorescence and western blot. Additionally, the effects of ATL III on synovial fibroblasts in vitro were evaluated through CCK-8 assays and migration assays to ascertain both cell viability and migratory behaviors. Furthermore, molecular docking studies were performed to elucidate the potential binding affinity of ATL III for Silent information regulator of transcription 1 (Sirt1), thereby providing insights into the underlying molecular mechanisms implicated in fibrosis modulation.</div></div><div><h3>Results</h3><div>ATL III treatment was observed to reduce proliferating cells, inflammatory cells and collagen accumulation in a rat model of traumatic rat knee fibrosis. In vitro, ATL III treatment was found to significantly reduce fibrosis and collagen-associated protein expression and inhibit synovial fibroblast proliferation and migration. Molecular docking identified Sirt1 as a potential target of ATL III. Interestingly, Sirt1 and Smad3 can interact and act to deacetylate Smad3, and in vitro and in vivo ATL III treatment significantly reduced Smad3 acetylation levels.</div></div><div><h3>Conclusion</h3><div>ATL III produces a therapeutic effect on knee fibrosis probably because Sirt1 deacetylates Smad3 and thus relieves knee fibrosis in rats.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"201 ","pages":"Article 112708"},"PeriodicalIF":3.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of daily steps and step intensity with peripheral arterial disease in Chinese community-dwelling older women","authors":"Chenfei Li ,&nbsp;Litao Du ,&nbsp;Xiangli Xue ,&nbsp;Na Zhao ,&nbsp;Qiang He ,&nbsp;Si Chen ,&nbsp;Xianliang Zhang","doi":"10.1016/j.exger.2025.112706","DOIUrl":"10.1016/j.exger.2025.112706","url":null,"abstract":"<div><h3>Aims</h3><div>This study aims to investigate the associations of objectively measured daily steps and step intensity with peripheral arterial disease (PAD) in Chinese community-dwelling older women.</div></div><div><h3>Methods</h3><div>Cross-sectional data were derived from the baseline survey of the Physical Activity and Health in Older Women Study. Peripheral arterial disease was evaluated through ankle-brachial index (ABI), ABI ≤ 0.9 was defined as cut-off point. Daily steps and step intensity were measured via tri-axial accelerometers. Multivariate logistic regression was used to investigate associations of step variable with PAD. Receiver operating characteristic (ROC) analysis was applied to identify an optimal cut-off value for step variables to screen PAD.</div></div><div><h3>Results</h3><div>After adjusting for confounding factors, it was found that daily steps was not independently associated with PAD, and brisk steps, peak 30 as well as peak 60, were significantly associated with PAD, with ORs of 0.68 (0.50–0.93), 0.71 (0.52–0.96) and 0.60 (0.40–0.90), respectively. The optimal cut-off values for brisk steps, peak 30 and 60 screening PAD were 952.3 steps, 76.7 steps/min and 51.8 steps/min, respectively.</div></div><div><h3>Conclusions</h3><div>Step intensity rather than daily steps was independently associated with PAD in Chinese community-dwelling older women. Increasing the intensity during walking may be a viable strategy to reduce the risk of PAD in self-care and cardiovascular nursing.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"201 ","pages":"Article 112706"},"PeriodicalIF":3.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoglobulin G4-related disease with pleural involvement in an 80-year-old female patient: A case report and literature review","authors":"Liying Zhang,&nbsp;Li Mo","doi":"10.1016/j.exger.2025.112707","DOIUrl":"10.1016/j.exger.2025.112707","url":null,"abstract":"<div><h3>Background</h3><div>Immunoglobulin G4-related disease (IgG4-RD), a rare immune-mediated disease affecting multiple organs, rarely involves the pleura. This study presents a case of pleural IgG4-RD and reviews the literature to elucidate the patient population, manifestations, and diagnostic and treatment characteristics of pleural IgG4-RD. This study aimed to expand the existing case database of pleural IgG4-RD and enhance the understanding and management of this rare disease.</div></div><div><h3>Methods</h3><div>We report a case of IgG4-RD involving the pleura in an 80-year-old woman with a weight of 62 kg and a body mass index (BMI) of 23.2 kg/m². Additionally, we reviewed pleural biopsy-confirmed IgG4-RD cases in the PubMed, Scopus, Web of Science, Embase, and Science Direct databases.</div></div><div><h3>Results</h3><div>Forty-one patients with IgG4-RD confirmed by pleural biopsy were included. The median age was 69 years, with male predominance (31, 75.6 %). The most common manifestations were pleural effusion (37, 90.2 %) and dyspnea (26, 63.4 %). Elevated serum IgG4 levels were observed in 38 patients (92.7 %), with a median value of 398.2 mg/dL. Twenty-six patients met two histological criteria for IgG4-RD. Thirty-seven patients received glucocorticoid therapy, 34 of whom achieved clinical improvement.</div></div><div><h3>Conclusions</h3><div>IgG4-RD with pleural involvement mainly manifests as pleural effusion and dyspnea, responding to glucocorticoid therapy. The possibility of this disease should be considered in patients with pleural effusion and enlargement of tissues or organs. Medical staff should attach importance to the application of the Comprehensive Geriatric Assessment (CGA) and the Geriatric Interdisciplinary Team (GIT) in the disease management of older patients.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"201 ","pages":"Article 112707"},"PeriodicalIF":3.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCSK9 affects vascular senescence through the SIRT1 pathway","authors":"Yuqin Wang ,&nbsp;Shaoqing Cao ,&nbsp;Zhangyu Wang ,&nbsp;Chengsi Li ,&nbsp;Jiangping Ye ,&nbsp;Yehong Liu ,&nbsp;Tianhui Jin ,&nbsp;Yuting Zhou ,&nbsp;Wentao Su ,&nbsp;Gangjun Zong","doi":"10.1016/j.exger.2025.112701","DOIUrl":"10.1016/j.exger.2025.112701","url":null,"abstract":"<div><div>Age is an independent risk factor for atherosclerotic cardiovascular disease that increases the susceptibility of older adults to vascular intimal thickening, endothelial dysfunction, and thrombosis. However, the mechanism underlying vascular injury is not fully understood. In the present study, the effect of proprotein convertase subtilin-type kexin 9 (PCSK9) inhibitors on the senescent state of human umbilical vein endothelial cells (HUVECs) and on senescent mice and lipopolysaccharides (LPS) were assessed. The senescent state of mice was delayed under PCSK9 inhibitor treatment, and the expression of P16, P21, and P53 proteins in senescent cells was increased because LPS induction stimulated PCSK9 activation. PCSK9 overexpression accelerated cell senescence, activated a large number of oxidative stress pathways, and increased the expression of senescence-related genes (including <em>P16</em>, <em>P21</em>, and <em>P53</em>). In addition, inhibition of the sirtuin 1 (SIRT)1 oxidative stress pathway can attenuate the aging-promoting effects of PCSK9, which are elevated as a result of LPS induction.</div><div>The SIRT1 activator was more efficient than LPS alone in inducing the expression of senescence-related genes. Therefore, PCSK9 inhibitors can delay the aging of the vascular by reducing cellular SIRT1 levels. Therefore, it can be concluded that PCSK9 inhibition inhibits vascular senescence by reducing the expression of senescent proteins by regulating the SIRT1 pathway.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"201 ","pages":"Article 112701"},"PeriodicalIF":3.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}