The Journals of Gerontology Series A: Biological Sciences and Medical Sciences最新文献_第3页

The function and regulation of celsr1a in skeletal age-associated homeostasis and repair in zebrafish. celsr1a在斑马鱼骨骼年龄相关稳态和修复中的功能和调控。

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Pub Date : 2025-04-29 DOI: 10.1093/gerona/glaf091

Joao Castro,Kira Fagerstrom,Stephen Treaster,Jeffrey Duryea,Julia Charles,Matthew P Harris

{"title":"The function and regulation of celsr1a in skeletal age-associated homeostasis and repair in zebrafish.","authors":"Joao Castro,Kira Fagerstrom,Stephen Treaster,Jeffrey Duryea,Julia Charles,Matthew P Harris","doi":"10.1093/gerona/glaf091","DOIUrl":"https://doi.org/10.1093/gerona/glaf091","url":null,"abstract":"The decrease of tissue resiliency with aging is due, in part, to changes in the retention of stem cell/progenitor populations that act to restore and maintain tissue quality with age or injury. In mice, the Celsr1 gene has been identified as a regulator of quiescent stem cells, while in zebrafish, celsr1a mutants demonstrate an essential function in maintaining adult stem cell populations within the highly proliferative tissues of the gut and skin. Here, we investigate the role of celsr1a as a regulator of adult skeletal stem cells and mediator of skeletal homeostasis and repair. We find that celsr1a is essential for maintenance of bone mineral density and volume in adult zebrafish. Using an enhancer screen to identify tissue/cell-specific regulators of celsr1a, we identified enhancers active in specific tissues that reflect the normal expression of celsr1a. We characterized C1a-A an enhancer that is active within stem/progenitor cells of diverse tissues. Consistent with this role, C1a-A marks specific cells in mature skeletal structures of the zebrafish, residing on the endosteal surface of zebrafish vertebrae and fin long-bones. These cells are limited in number and contribute to osteocyte populations within the bony matrix. Using a novel long bone fracture assay in adult zebrafish, we find that celsr1a positive skeletal cells respond to damage and that celsr1a function is essential for fracture healing. Our investigation details an unexpected role of cels1a in skeletal repair and quality with age and highlights a new regulator of stem cell activity in the skeleton.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889277","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}

引用次数: 0

Adherence to a planetary health diet, diet-related greenhouse gas emissions, functional disability, and mortality in older adults 坚持全球健康饮食、与饮食有关的温室气体排放、功能性残疾和老年人死亡率

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Pub Date : 2025-04-28 DOI: 10.1093/gerona/glaf089

Daiki Watanabe, Tsukasa Yoshida, Hinako Nanri, Yuya Watanabe, Chiho Goto, Kazuko Ishikawa-Takata, Yosuke Yamada, Motohiko Miyachi, Misaka Kimura

{"title":"Adherence to a planetary health diet, diet-related greenhouse gas emissions, functional disability, and mortality in older adults","authors":"Daiki Watanabe, Tsukasa Yoshida, Hinako Nanri, Yuya Watanabe, Chiho Goto, Kazuko Ishikawa-Takata, Yosuke Yamada, Motohiko Miyachi, Misaka Kimura","doi":"10.1093/gerona/glaf089","DOIUrl":"https://doi.org/10.1093/gerona/glaf089","url":null,"abstract":"Background Previous epidemiological studies have revealed a relationship among planetary health diets (PHDs), diet-related greenhouse gas emissions (GHGEs), and mortality. However, these studies did not include older adults from non-Western countries. This study examined these associations in Japanese older adults. Methods This prospective study included 8043 adults aged ≥65 years from the Kyoto–Kameoka study in Japan. Dietary intake was estimated using a validated food frequency questionnaire. Adherence to PHDs was evaluated by calculating the EAT-Lancet index [range, 0 (worst) to 42 (best)], which were classified into four categories: ≤25 (n = 1061; very low), 26–27 (n = 1703; low), 28–30 (n = 3368; moderate), and ≥31 (n = 1911; high) points. Diet-related GHGEs were calculated using previously developed GHGE tables for each food item. Results During the median 4.75-year follow-up period, 659 deaths and 1431 incidents of functional disability were recorded. After adjusting for confounders, the hazard ratios (HRs) of mortality were lower in the moderate-adherence group than in the very low-adherence group (HR, 0.64; 95% confidence interval, 0.60–0.93). PHD scores tended to be inversely associated with functional disability (p for trend = 0.081). However, diet-related GHGEs were not associated with mortality or disability. The PHD score ranges with the lowest HRs for mortality and mean diet-related GHGE were 28–30 and 29–31 points, respectively. Conclusions Moderate adherence to current PHD is inversely associated with diet-related GHGE and mortality risk. This underscores the importance of dietary shifts for improving public health and environmental sustainability.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"221 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880375","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}

引用次数: 0

Effect of Excessive daytime sleepiness and long sleep duration on all cause dementia: a systematic review and meta-analysis 白天过度嗜睡和长时间睡眠对全因痴呆的影响：一项系统回顾和荟萃分析

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Pub Date : 2025-04-28 DOI: 10.1093/gerona/glaf087

Kay Khaing, Xenia Dolja-Gore, Joshua Dizon, Xinying Fang, Zizhong Tian, Chenqi Fu, Daniel Barker, Shouhao Zhou, Balakrishnan R Nair, Julie Byles, John Attia

{"title":"Effect of Excessive daytime sleepiness and long sleep duration on all cause dementia: a systematic review and meta-analysis","authors":"Kay Khaing, Xenia Dolja-Gore, Joshua Dizon, Xinying Fang, Zizhong Tian, Chenqi Fu, Daniel Barker, Shouhao Zhou, Balakrishnan R Nair, Julie Byles, John Attia","doi":"10.1093/gerona/glaf087","DOIUrl":"https://doi.org/10.1093/gerona/glaf087","url":null,"abstract":"Background Excessive daytime sleepiness (EDS) and long sleep duration are common in older adults and are related to dementia pathology. This study aims to assess the effect of EDS and long sleep duration on all-cause dementia and cognitive decline. Methods We identified longitudinal studies assessing the relationship between EDS and/or long sleep duration on cognitive decline/dementia published up to March 24, 2024 from MEDLINE, Embase, PsyINFO, the Cochrane Central Register of Controlled Trials, and PubMed. The inverse-variance-weighted average method and Bayesian multilevel regression models were used to test the effect of EDS and long sleep duration on cognitive decline and dementia risk. Results 15 studies with 65501 participants were recruited. EDS was associated with increased risk of cognitive decline and all-cause dementia (Risk Ratio (RR)1.26, 95% Confidence Interval (CI) 1.13-1.41, and RR 1.68, 95% CI 1.07-2.66, respectively). Long sleep duration increased the risk of all-cause dementia by 29% (95% Hazard Ratio (HR) CI: 0.94 - 1.77, Pr (HR&gt;1) = 0.94); and cognitive decline by 13% (95% RR CI: 0.92 - 1.4). Dementia-free time at age 85 was 0.13 years shorter among long sleepers (Pr (∆Restricted Mean Dementia-Free Time (RMDFT) &lt; 0) = 0.98). Conclusions Both EDS and long sleep duration were associated with increased risk of all-cause dementia. However, it remains unclear whether these are independent risk factors or merely reflect the same underlying pathological process. Further studies are needed to explore the interaction between these exposures on dementia and their potential as targets for dementia prevention.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884608","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}

引用次数: 0

Gray Matter Covariance Networks Associated with Parental Longevity – Results from the LonGenity Study 与父母寿命相关的灰质协方差网络——来自长寿研究的结果

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Pub Date : 2025-04-28 DOI: 10.1093/gerona/glaf066

Natalie Delpratt, Nir Barzilai, Sofiya Milman, Sandra Aleksic, Erica Weiss, Joe Verghese, Helena M Blumen

{"title":"Gray Matter Covariance Networks Associated with Parental Longevity – Results from the LonGenity Study","authors":"Natalie Delpratt, Nir Barzilai, Sofiya Milman, Sandra Aleksic, Erica Weiss, Joe Verghese, Helena M Blumen","doi":"10.1093/gerona/glaf066","DOIUrl":"https://doi.org/10.1093/gerona/glaf066","url":null,"abstract":"Background Older adults with exceptional longevity – and their offspring – are protected from age-related diseases and have a prolonged health span. Prior research suggests that offspring of parents with exceptional longevity have larger temporal and sensorimotor cortices in mid to late-adulthood – but the association between brain health and parental longevity is not well understood in older adults. This study aimed to identify a gray matter volume pattern (or network) associated with parental longevity in older adults - and to determine if individual expressions of this gray matter pattern vary with cognitive performance. Methods Participants consisted of one hundred and thirty-nine older adults of Ashkenazi Jewish descent from the LonGenity study (M Age 79.4±6.5 years; 56.11% women). Eighty-four (60.4%) were offspring of parents with exceptional longevity and 55 (39.6%) were offspring of parents with usual survival. A gray matter network associated with parental longevity was derived with multivariate covariance-based analyses that were adjusted for potential confounders. Participant-specific expressions of this network were then regressed against cognitive test performances. Results The derived gray matter covariance network associated with parental longevity was primarily composed of frontal, insular, and hippocampal regions. The extent to which older adults displayed this pattern was associated with overall cognition, Free Recall, Digit Symbol Substitution, Boston Naming and Trail Making Test A performance. Conclusion Parental longevity is associated with a widespread network of brain regions in aging. This brain network also varies as a function of cognitive performance.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880374","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}

引用次数: 0

Elucidating Cellular Senescence-related Genes in Benign Prostatic Hyperplasia through Mendelian Randomization and Single-cell RNA Sequencing. 通过孟德尔随机化和单细胞 RNA 测序阐明良性前列腺增生症中的细胞衰老相关基因

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Pub Date : 2025-04-23 DOI: 10.1093/gerona/glaf073

Yichuan Wang,Liang Zhou,Jiahao Liu,Qing Zhou,Wei Xiong,Long Wang

{"title":"Elucidating Cellular Senescence-related Genes in Benign Prostatic Hyperplasia through Mendelian Randomization and Single-cell RNA Sequencing.","authors":"Yichuan Wang,Liang Zhou,Jiahao Liu,Qing Zhou,Wei Xiong,Long Wang","doi":"10.1093/gerona/glaf073","DOIUrl":"https://doi.org/10.1093/gerona/glaf073","url":null,"abstract":"BACKGROUNDBenign prostatic hyperplasia (BPH) is a widely observed disorder in older men, with substantial evidence indicating that cellular senescence serves a pivotal function in its progression. This investigation seeks to pinpoint cellular senescence-related genes causally connected with BPH and to examine their expression and regulatory networks across distinct prostate cells.METHODSUsing exposure data from the eQTLGen database and outcome data from both FinnGen Consortium and UKB database, Mendelian randomization (MR) was utilized to determine cell senescence genes that are causally linked to BPH. These associations were further validated through co-localization analysis. Expression patterns of these genes in different prostate cells were assessed via single-cell RNA sequencing (scRNA-seq), and changes along pseudotime were tracked. Regulatory networks were evaluated using SCENIC to identify key transcription factors involved.RESULTSSix cell senescence genes causally linked to BPH were identified through MR. ATM, ATRAID, MAP2K1, and TP53 were identified as protective factors, whereas ITPR1 and SENP7 were associated with increased risk. Co-localization analysis suggested that ATM and TP53 are likely to share the same variant implicated in BPH. MAP2K1 expression demonstrated a steady decline along inferred pseudotime across fibroblasts, macrophages, T cells, and epithelial cells, while the remaining five genes exhibited an opposite trend. ATF3, EGR1, and FOS were pinpointed as the core transcription factors regulating these genes.CONCLUSIONSThese observations emphasize consistent expression patterns among different prostate cell types and suggest a highly interconnected regulatory network that underpins BPH pathology, thereby providing fresh perspectives on the molecular mechanisms underlying the disease.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871985","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}

引用次数: 0

Association of epigenetic markers of ageing with prevalent and incident type 2 diabetes. 衰老的表观遗传标记与流行和发生的2型糖尿病的关联。

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Pub Date : 2025-04-21 DOI: 10.1093/gerona/glaf085

Danmeng Lily Li,Allison M Hodge,Melissa C Southey,Graham G Giles,Pierre-Antoine Dugué

{"title":"Association of epigenetic markers of ageing with prevalent and incident type 2 diabetes.","authors":"Danmeng Lily Li,Allison M Hodge,Melissa C Southey,Graham G Giles,Pierre-Antoine Dugué","doi":"10.1093/gerona/glaf085","DOIUrl":"https://doi.org/10.1093/gerona/glaf085","url":null,"abstract":"BACKGROUNDType 2 diabetes (T2D) is characterised by elevated levels of metabolic and inflammatory markers but less is known about other molecular alterations that occur with ageing. We aimed to assess the associations of DNA methylation-based measures of ageing (epigenetic ageing) with prevalent and incident T2D in a large sample of middle-aged and older Australians.METHODSWe used data from 5403 participants in the Melbourne Collaborative Cohort Study (mean age=59 years). Five blood-based epigenetic ageing measures: PCPhenoAge, PCGrimAge, DNAmFitAge, bAge, and DunedinPACE were calculated. T2D status was assessed at baseline (1990-1994, Ncases=180) and two waves of follow-up (1995-1998, Ncases=134; 2003-2007, Ncases=244). Modified Poisson regression models were used to estimate risk ratios (RRs) for the associations of epigenetic age with prevalent and incident T2D.RESULTSA standard deviation increase in epigenetic age was associated with 1.11-fold (PCPhenoAge, 95%CI: 0.98-1.26) to 1.33-fold (bAge, 95%CI: 1.12-1.57) higher prevalence of T2D at baseline. Prospectively, DunedinPACE showed the strongest association with incident T2D at follow-up 2 (RR=1.22, 95%CI: 1.07-1.38). These estimates were slightly attenuated but consistent in sensitivity analyses reclassifying participants who reported being T2D-free but had high glucose concentrations (>7mmol/L for fasting glucose, >11.1mmol/L for non-fasting glucose). No evidence of increased epigenetic age was found for participants with pre-T2D (>5.6mmol/L for fasting glucose, >7.8mmol/L for non-fasting glucose). The positive associations between epigenetic age and fasting glucose levels appeared stronger in participants with T2D.CONCLUSIONSIn middle-aged and older Australians, epigenetic age, in particular as assessed by bAge and DunedinPACE, was positively associated with prevalent and incident T2D. Our findings may have implications for understanding of the aetiology and management of T2D.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857258","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}

引用次数: 0

Temporal dynamics of intrinsic brain activity in older women with subclinical depression. 老年女性亚临床抑郁症患者内在脑活动的时间动态。

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Pub Date : 2025-04-18 DOI: 10.1093/gerona/glaf084

Jing Jiang,Lei Li,Xueling Suo,Taolin Chen,Stefania Ferraro,Jin Gao,Dongmei Wu,Song Wang

{"title":"Temporal dynamics of intrinsic brain activity in older women with subclinical depression.","authors":"Jing Jiang,Lei Li,Xueling Suo,Taolin Chen,Stefania Ferraro,Jin Gao,Dongmei Wu,Song Wang","doi":"10.1093/gerona/glaf084","DOIUrl":"https://doi.org/10.1093/gerona/glaf084","url":null,"abstract":"Subclinical depression is common in older adults, especially in females, and may correlate with a higher likelihood of health events and poor prognosis. However, the underlying neurobiology remains unclear. This study, employing resting-state functional magnetic resonance imaging (rs-fMRI), identified alterations in temporal dynamics of intrinsic brain activity in older women with subthreshold depression (OWSD) and their potential relationships to depressive symptoms. The sliding window approach was applied to evaluate the temporal variations of the rs-fMRI indices, including the amplitude of low-frequency fluctuation (ALFF), the fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC) in 50 OWSD and 52 healthy older women controls (HOWC). We then calculated the dynamic voxel-wise concordance index of the rs-fMRI indices. The correlational analyses were used to assess the correlations between the dynamic indices and depressive symptoms. We found that OWSD showed a significant increase in dynamic ALFF (dALFF) in the left dorsolateral prefrontal cortex (DLPFC) relative to HOWC. With respect to regional brain function integration, OWSD showed a significantly lower dynamic voxel-wise concordance index in the right parietal lobe, mainly including the precuneus and superior parietal lobule extending to the postcentral gyrus. The regional dALFF and dynamic concordance index alterations were correlated with depressive symptoms. In conclusion, OWSD showed depression-correlated alterations in temporal variability of intrinsic brain activity, along with regional deficits in brain function integration. The findings reinforce our understanding of subthreshold depression psychopathology in older women.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"108 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849541","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}

引用次数: 0

A systematic review and meta-analysis highlights a link between aerobic fitness and telomere maintenance 一项系统综述和荟萃分析强调了有氧健身和端粒维持之间的联系

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Pub Date : 2025-04-18 DOI: 10.1093/gerona/glaf068

Clodagh Ryall, Joshua Denham

{"title":"A systematic review and meta-analysis highlights a link between aerobic fitness and telomere maintenance","authors":"Clodagh Ryall, Joshua Denham","doi":"10.1093/gerona/glaf068","DOIUrl":"https://doi.org/10.1093/gerona/glaf068","url":null,"abstract":"Cardiorespiratory fitness declines with ageing and is a major risk factor of cardiometabolic diseases and early death. Although the benefits of regular exercise are well established, whether maximal oxygen uptake (V̇O2max) is associated with biological ageing remains unclear. Given that telomere shortening is a hallmark of ageing, the purpose of this systematic review and meta-analysis was to determine the association between V̇O2max and telomere length. Articles were retrieved from PubMed, Scopus, and ScienceDirect and deemed eligible if they: 1) involved human participants with relatively low and high V̇O2max values objectively assessed by pulmonary analysis; 2) quantified telomere length using an established technique; and 3) were peer-reviewed journal articles written in English. Relative to individuals with below average V̇O2max based on age- and sex-adjusted norms, fit participants with relative V̇O2max values in the 70th percentile or higher possessed longer telomeres (SMD [95%CI]: 0.36 [0.14–0.59], p=0.002). A similar difference was observed between individuals with below average V̇O2max and those above the 90th percentile (0.28 [0.03–0.53], p=0.03). However, no statistically significant telomere length differences were observed between individuals in the 70th to 90th percentile compared to those above the 90th (-0.08 [-0.40–0.24], p=0.62). The findings provide evidence linking metabolism to telomere biology. They encourage individuals to regularly engage in endurance exercise to attenuate telomere attrition and promote healthy biological ageing. Importantly, the results suggest that extensive endurance training may not be required to protect the telomeres, rather moderate amounts of training may be sufficient to reach more achievable V̇O2max targets.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847140","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}

引用次数: 0

Identifying causal brain structures, genes and proteins for osteoarthritis: A large-scale genetic correlation study based on brain imaging-derived phenotypes, transcriptomes, and proteomes 鉴定骨关节炎的因果脑结构、基因和蛋白质：基于脑成像衍生表型、转录组和蛋白质组的大规模遗传相关性研究

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Pub Date : 2025-04-18 DOI: 10.1093/gerona/glaf083

Chao Wang, Zhi Liu, Yong Zhu, Zhe Ruan, Haitao Long, Zhangyuan Lin, Ruibo Zhao, Wenfeng Xiao, Yusheng Li, Shushan Zhao

{"title":"Identifying causal brain structures, genes and proteins for osteoarthritis: A large-scale genetic correlation study based on brain imaging-derived phenotypes, transcriptomes, and proteomes","authors":"Chao Wang, Zhi Liu, Yong Zhu, Zhe Ruan, Haitao Long, Zhangyuan Lin, Ruibo Zhao, Wenfeng Xiao, Yusheng Li, Shushan Zhao","doi":"10.1093/gerona/glaf083","DOIUrl":"https://doi.org/10.1093/gerona/glaf083","url":null,"abstract":"Background Recent epidemiological studies have linked the central nervous system (CNS) to osteoarthritis (OA), suggesting that targeting the CNS could offer new therapeutic strategies. This study aimed to validate the correlation between brain structures and OA risk, and to identify key causal genes by integrating brain transcriptomic and proteomic data with OA genome-wide association studies (GWAS). Methods We analyzed OA summary statistics from 826,690 participants. Using linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR), we explored the genetic relationships between brain structures and OA. A transcriptome-wide association study (TWAS) was conducted with 5,138 brain transcriptomes. Additionally, a proteome-wide association study (PWAS) combined GWAS data with 152 human brain proteomes. Single-cell RNA-Seq eQTL data helped identify causal genes in brain cells linked to OA. Results LDSC and MR indicated brain structures, such as the putamen and amygdala, are strongly associated with OA. Seven genes were linked to knee OA and four to hip OA (FDR &lt; 0.05). Proteins associated with knee, hip, and thumb OA were also identified. scRNA analysis revealed CPNE1 in excitatory neurons and EMILIN2 in oligodendrocyte progenitor cells as causally linked to knee OA. Conclusions This study enhances our understanding of the brain-joint axis in OA genetics, potentially informing new treatment strategies and therapeutic targets.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847116","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}

引用次数: 0

The effect of vitamin D3 supplementation on the incidence of diagnosed dementia among healthy older adults – the Finnish Vitamin D Trial 补充维生素D3对健康老年人诊断痴呆发病率的影响——芬兰维生素D试验

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Pub Date : 2025-04-17 DOI: 10.1093/gerona/glaf077

Eija Lönnroos, Maija Ylilauri, Christel Lamberg-Allardt, Jo Ann E Manson, Tarja Nurmi, Matti Uusitupa, Ari Voutilainen, Sari Hantunen, Tomi-Pekka Tuomainen, Jyrki K Virtanen

{"title":"The effect of vitamin D3 supplementation on the incidence of diagnosed dementia among healthy older adults – the Finnish Vitamin D Trial","authors":"Eija Lönnroos, Maija Ylilauri, Christel Lamberg-Allardt, Jo Ann E Manson, Tarja Nurmi, Matti Uusitupa, Ari Voutilainen, Sari Hantunen, Tomi-Pekka Tuomainen, Jyrki K Virtanen","doi":"10.1093/gerona/glaf077","DOIUrl":"https://doi.org/10.1093/gerona/glaf077","url":null,"abstract":"Background Some short-term vitamin D supplementation trials suggest benefits on cognitive performance, but apart from observational studies, there is little evidence whether long-term vitamin D supplementation can prevent development of dementia. We investigated whether vitamin D3 supplementation could affect the incidence of diagnosed dementia in a generally healthy population. Methods The study included 2492 participants from the Finnish Vitamin D Trial, free of diagnosed dementia at baseline. They were randomized to placebo, 1600 IU/day or 3200 IU/day of vitamin D3 arm for up to 5 years. Incident diagnoses of dementia were obtained from the national care registries. Results The mean age of the participants at baseline was 68.2 y and 42.8% were female. During the mean follow-up of 4.2 y, 18 participants in the placebo arm, 14 participants in the 1600 IU/day arm (compared to placebo, hazard ratio [HR]=0.77, 95% confidence interval [CI] 0.38-1.55) and 13 participants in the 3200 IU/day arm (HR=0.72, 95% CI 0.35-1.48) were diagnosed with dementia. Of the diagnoses, 29 were Alzheimer’s disease, without statistically significant differences in the event rates between the three arms. Age, sex, or body mass index did not modify the effects. In the subgroup of 550 participants, the mean baseline serum 25-hydroxyvitamin D concentration was 74.8 nmol/L. After 12 months, the mean concentrations were 73.0, 99.7 and 120.4 nmol/L, in the placebo, 1600 IU/day and 3200 IU/day arms, respectively. Conclusions Five-year, medium-dose or high-dose vitamin D3 supplementation did not affect the dementia incidence in this largely vitamin D sufficient older population.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841358","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}

引用次数: 0