The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

{"title":"Intestinal Permeability, Gut Inflammation, and Gut Immune System Response Are Linked to Aging-Related Changes in Gut Microbiota Composition: A Study in Female Mice.","authors":"Paola Elizabeth Gámez-Macías, Elisa Félix-Soriano, Mirian Samblas, Neira Sáinz, María Jesús Moreno-Aliaga, Pedro González-Muniesa","doi":"10.1093/gerona/glae045","DOIUrl":"10.1093/gerona/glae045","url":null,"abstract":"<p><p>Aging entails changes at the cellular level that increase the risk of various pathologies. An association between gut microbiota and age-related diseases has also been attributed. This study aims to analyze changes in fecal microbiota composition and their association with genes related to immune response, gut inflammation, and intestinal barrier impairment. Fecal samples of female mice at different ages (2 months, 6 months, 12 months, and 18 months) and gene expression in colon tissue were analyzed. Results showed that the older mice group had a more diverse microbiota than the younger group. Additionally, the abundance of Cyanobacteria, Proteobacteria, Flavobacteriaceae, Bacteroides, Parabacteroides, Prevotellaceae_UCG-001, Akkermansia, and Parabacteroides goldsteinii increased with age. In contrast, there was a notable decline in Clostridiaceae, Lactobacillaceae, Monoglobaceae, Ligilactobacillus, Limosilactobacillus, Mucispirillum, and Bacteroides faecichinchillae. These bacteria imbalances were positively correlated with increased inflammation markers in the colon, including Tnf-α, Ccl2, and Ccl12, and negatively with the expression of tight junction genes (Jam2, Tjp1, and Tjp2), as well as immune response genes (Cd4, Cd72, Tlr7, Tlr12, and Lbp). In conclusion, high levels of diversity did not result in improved health in older mice; however, the imbalance in bacteria abundance that occurs with aging might contribute to immune senescence, inflammation, and leaky gut disease.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10957128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747993","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":"Joint Association of Physical Frailty and Self-Rated Health With Mortality Among Community-Dwelling Older Adults.","authors":"Chenkai Wu, Yichen Xu, Junhan Tang, Hua Liu, Qian-Li Xue","doi":"10.1093/gerona/glad286","DOIUrl":"10.1093/gerona/glad286","url":null,"abstract":"<p><strong>Background: </strong>The relationship between subjective and objective health is complex and not always matched. Although frailty and self-rated health (SRH) have been separately associated with adverse outcomes, their joint effects remained unclear.</p><p><strong>Methods: </strong>Participants were 5 300 adults ≥60 years from the China Health and Retirement Longitudinal Study in 2011. Frailty, measured by the validated physical frailty phenotype approach, was classified as nonfrail, prefrail, and frail. SRH was categorized into 3 groups: excellent/very good/good, fair, and poor/very poor. We used the Cox models to examine the independent and joint association of frailty and SRH with mortality. We used the interaction approach to determine whether the association of SRH with mortality differed by frailty. Subgroup analyses were conducted by depression and cognitive impairment.</p><p><strong>Results: </strong>About 8.1% of frail participants reported excellent/very good/good health; 21.2% of the nonfrail reported poor/very poor health. Prefrailty and frailty were associated with a 1.63- and 2.38-fold increase in the hazard of mortality than the nonfrail, respectively, after adjusting for SRH. Reporting fair and poor/very poor health was associated with a 29% and 100% increase in the hazard of mortality, respectively, after adjusting for frailty. No significant interaction was found. Prefrail and frail older adults with excellent/very good/good health had a similar mortality as the nonfrail with poor/very poor SRH. The association of SRH with mortality was less pronounced among individuals with depression or cognitive impairment.</p><p><strong>Conclusions: </strong>SRH is a potential marker of resilience among people living with frailty that may be a target for ameliorating health risks induced by frailty.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139050035","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":"SerpinA3N Regulates the Secretory Phenotype of Mouse Senescent Astrocytes Contributing to Neurodegeneration.","authors":"Xiaojuan Han, Qing Lei, Huanhuan Liu, Tianying Zhang, Xingchun Gou","doi":"10.1093/gerona/glad278","DOIUrl":"10.1093/gerona/glad278","url":null,"abstract":"<p><p>Senescent astrocyte accumulation in the brain during normal aging is a driver of age-related neurodegenerative diseases such as Alzheimer's disease. However, the molecular events underlying astrocyte senescence in Alzheimer's disease are not fully understood. In this study, we demonstrated that senescent astrocytes display a secretory phenotype known as the senescence-associated secretory phenotype (SASP), which is associated with the upregulation of various proinflammatory factors and the downregulation of neurotrophic growth factors (eg, NGF and BDNF), resulting in a decrease in astrocyte-mediated neuroprotection and increased risk of neurodegeneration. We found that SerpinA3N is upregulated in senescent primary mouse astrocytes after serial passaging in vitro or by H2O2 treatment. Further exploration of the underlying mechanism revealed that SerpinA3N deficiency protects against senescent astrocyte-induced neurodegeneration by suppressing SASP-related factors and inducing neurotrophic growth factors. Brain tissues from Alzheimer's disease model mice possessed increased numbers of senescent astrocytes. Moreover, senescent astrocytes exhibited upregulated SerpinA3N expression in vitro and in vivo, confirming that our cell model recapitulated the in vivo pathology of these neurodegenerative diseases. Altogether, our study reveals a novel molecular strategy to regulate the secretory phenotype of senescent astrocytes and implies that SerpinA3N and its regulatory mechanisms may be potential targets for delaying brain aging and aging-related neurodegenerative diseases.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089808","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":"Mental Health Impacts of COVID-19: Does Prepandemic Cognition and Dementia Status Matter?","authors":"Emma Nichols, Sarah Petrosyan, Jinkook Lee","doi":"10.1093/gerona/glae028","DOIUrl":"10.1093/gerona/glae028","url":null,"abstract":"<p><strong>Background: </strong>The coronavirus disease 2019 (COVID-19) pandemic disrupted daily life and led to sharp shocks in trends for various health outcomes. Although substantial evidence exists linking the pandemic and mental health outcomes and linking dementia and mental health outcomes, little evidence exists on how cognitive status may alter the impact of COVID-19 on mental health.</p><p><strong>Methods: </strong>We used prepandemic data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia study and 9 waves of data from the Real-Time Insights of COVID-19 in India study (N = 1 182). We estimated associations between measures of prepandemic cognition (continuous cognition based on 22 cognitive tests, dementia status) and mental health measures during the pandemic (Patient Health Questionnaire [PHQ]-4 [9 time points], PHQ-9 [2 time points], Beck Anxiety Inventory [3 time points]), adjusting for age, gender, rural/urban residence, state, education, and prepandemic mental health.</p><p><strong>Results: </strong>Summarizing across time points, PHQ-9 score was marginally or significantly associated with prepandemic cognition (PHQ-9 difference: -0.38 [-0.78 to 0.14] points per SD higher cognition; p = .06), and prepandemic dementia (PHQ-9 difference: 0.61 [0.11-1.13] points for those with dementia compared to no dementia; p = .02). Associations with BAI were null, whereas associations with PHQ-4 varied over time (p value for interaction = .02) and were strongest during the delta wave, when pandemic burden was highest.</p><p><strong>Conclusions: </strong>We present initial evidence that mental health impacts of COVID-19 or other acute stressors may be unequally distributed across strata of cognitive outcomes. In dynamically changing environments, those with cognitive impairment or dementia may be more vulnerable to adverse mental health outcomes.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10972580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547973","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":"Telomere Length Is a Driving Hallmark for Aging-Related Biochemical Hallmarks: Evidence From the Shared Genetic Effect and Causal Inference.","authors":"Ben Niu, Jia-Xin Wu, Xiao-Li Huang, Shu-Feng Lei, Fei-Yan Deng","doi":"10.1093/gerona/glad275","DOIUrl":"10.1093/gerona/glad275","url":null,"abstract":"<p><p>Telomere shortening is an important sign and driving factor of aging, but its association mechanisms and causal effects with other aging-related biochemical hallmarks are largely unknown. This study first performed comprehensive genetic analyses (eg, shared genetic analysis, pleiotropic analysis, and gene enrichment analysis) to detect the underlying molecular mechanisms for the associations between telomere length (TL) and aging-related biochemical hallmarks. Then, further bidirectional Mendelian randomization (MR) analyses investigated the causal effects between TL and other biochemical hallmarks. The genetic correlations were negative between TL and growth differentiation factor-15 (GDF15) (p = .024), C-reactive protein (p = .007), hemoglobin A1c (p = .007), and red blood cell (RBC) (p = .022), but positive between TL and insulin-like growth factor 1 (IGF-1) (p = .002) and white blood cell counts (p = .007). The increased TL has causal effects on the low levels of GDF15 (p = 3.73E-06), sex hormone binding globulin (p = 6.30E-06), testosterone (p = 5.56E-07), fasting insulin (p = 2.67E-05), and RBC (p = 1.54E-05), but the higher levels of IGF-1 (p = 3.24E-07). In conclusion, the observed phenotypic correlations between TL and aging-related biochemical hallmarks may arise from a combination of shared genetic components and causal effects. Telomere length is regarded as a driving hallmark for aging-related biochemical hallmarks.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138886857","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":"The Impact of Air Pollution on Physical Functioning Decline and the Benefits of Greenness: Evidence From a Nationwide Cohort Study.","authors":"Ke Zhang, Jie He, Zhongyang Chen, Mengnan Pan, Jiahui Tong, Dejian Kou, Feifei Liu, Hao Xiang","doi":"10.1093/gerona/glae042","DOIUrl":"10.1093/gerona/glae042","url":null,"abstract":"<p><strong>Background: </strong>Physical functional limitations (PFLs) increase the vulnerability of adults, but their pathogenesis remains unclear.</p><p><strong>Methods: </strong>We conducted a nationwide longitudinal study on 62 749 records from 18 878 adults (aged ≥45) from 28 provinces in China. Risk of PFLs was assessed using a validated 9-item questionnaire. Exposure levels of air pollutants (PM10, PM2.5, and PM1) and greenness (normalized difference vegetation index, NDVI) were estimated using a satellite-based spatiotemporal model. We used the cumulative link mixed effects model to estimate the associations between short-term and long-term exposure to air pollutants, greenness, and risk of PFLs. We employed the interaction effect model to evaluate interactions between air pollutants and greenness.</p><p><strong>Results: </strong>Participants were 60.9 ± 9.6 years, with an average follow-up of 5.87 (1.65) years. Exposure to air pollution was significantly associated with a higher risk of PFLs. For instance, the odds ratio (OR) associated with each 10 μg/m3 higher in 6-month averaged PM10, PM2.5, and PM1 were 1.025 (95% CI: 1.015-1.035), 1.035 (95% CI: 1.018-1.054), and 1.029 (95% CI: 1.007-1.050), respectively. Conversely, exposure to greenness was associated with decreased risk of PFLs; the OR associated with each 1-unit higher in 1-year averaged NDVI was 0.724 (95% CI: 0.544-0.962). Furthermore, higher greenness levels were found to mitigate the adverse effects of 1-year, 6-month, 1-month averaged PM10, and 1-year averaged PM2.5 on the risk of PFLs.</p><p><strong>Conclusions: </strong>Air pollution raises the risk of PFLs, whereas greenness could mitigate the adverse effects. Reducing air pollution and enhancing greenness could prevent physical functioning.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139907259","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":"Abdominal Body Composition Reference Ranges and Association With Chronic Conditions in an Age- and Sex-Stratified Representative Sample of a Geographically Defined American Population.","authors":"Alexander D Weston, Brandon R Grossardt, Hillary W Garner, Timothy L Kline, Alanna M Chamberlain, Alina M Allen, Bradley J Erickson, Walter A Rocca, Andrew D Rule, Jennifer L St Sauver","doi":"10.1093/gerona/glae055","DOIUrl":"10.1093/gerona/glae055","url":null,"abstract":"<p><strong>Background: </strong>Body composition can be accurately quantified from abdominal computed tomography (CT) exams and is a predictor for the development of aging-related conditions and for mortality. However, reference ranges for CT-derived body composition measures of obesity, sarcopenia, and bone loss have yet to be defined in the general population.</p><p><strong>Methods: </strong>We identified a population-representative sample of 4 900 persons aged 20 to 89 years who underwent an abdominal CT exam from 2010 to 2020. The sample was constructed using propensity score matching an age and sex stratified sample of persons residing in the 27-county region of Southern Minnesota and Western Wisconsin. The matching included race, ethnicity, education level, region of residence, and the presence of 20 chronic conditions. We used a validated deep learning based algorithm to calculate subcutaneous adipose tissue area, visceral adipose tissue area, skeletal muscle area, skeletal muscle density, vertebral bone area, and vertebral bone density from a CT abdominal section.</p><p><strong>Results: </strong>We report CT-based body composition reference ranges on 4 649 persons representative of our geographic region. Older age was associated with a decrease in skeletal muscle area and density, and an increase in visceral adiposity. All chronic conditions were associated with a statistically significant difference in at least one body composition biomarker. The presence of a chronic condition was generally associated with greater subcutaneous and visceral adiposity, and lower muscle density and vertebrae bone density.</p><p><strong>Conclusions: </strong>We report reference ranges for CT-based body composition biomarkers in a population-representative cohort of 4 649 persons by age, sex, body mass index, and chronic conditions.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10949446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139907258","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":"Predictors of Frailty Transitions in Mexican Older Adults.","authors":"Ana Rivera-Almaraz, Aarón Salinas-Rodríguez, Eduardo Gutiérrez-Peña, Betty Soledad Manrique-Espinoza","doi":"10.1093/gerona/glae068","DOIUrl":"10.1093/gerona/glae068","url":null,"abstract":"<p><strong>Background: </strong>Frailty is a dynamic state in older adults. Current evidence, mostly in high-income countries, found that improving frailty is more likely in mild states (prefrailty). We aimed to determine the probability of frailty transitions and their predictors.</p><p><strong>Methods: </strong>Participants were adults aged 50 years or over from the Study on Global Ageing and Adult Health in Mexico during 4 waves (2009, 2014, 2017, and 2021). We defined frailty with the frailty phenotype and we used multinomial logistic models to estimate the probabilities of frailty transitions and determine their predictors.</p><p><strong>Results: </strong>For the 3 analyzed periods (2009-2014, 2014-2017, and 2017-2021), transition probabilities from frail to robust were higher for the younger age group (50-59 years) at 0.20, 0.26, and 0.20, and lower for the older age group (≥80 years), 0.03, 0.08 and 0.04. Transitioning from prefrail to robust had probabilities of 0.38, 0.37, and 0.35, for the younger age group, and 0.09, 0.18, and 0.10, for the older age group. The probabilities of transitioning to frail and to death were lower for the younger age group and for the robust at baseline; but higher for the older age group and for the frail at baseline. We identified age, disability, and diabetes as the most significant predictors of frailty transitions.</p><p><strong>Conclusions: </strong>These findings show that frailty has a dynamic nature and that a significant proportion of prefrail and frail individuals can recover to a robust or prefrail state. They also emphasize that prefrailty should be the focus of interventions.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10949440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944797","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":"Hazardous Alcohol Use Among Community-Dwelling Older Adults With Persistent or Recurrent Pain: Findings From the Health and Retirement Study.","authors":"Lisa R LaRowe, Angela Miller, Sachin J Shah, Christine S Ritchie","doi":"10.1093/gerona/glad281","DOIUrl":"10.1093/gerona/glad281","url":null,"abstract":"<p><strong>Background: </strong>Although pain and alcohol use are highly prevalent and associated with deleterious health outcomes among older adults, a paucity of literature has examined hazardous drinking among older adults with pain. We aimed to examine the prevalence of hazardous drinking among a nationally representative sample of older adults with persistent or recurrent pain.</p><p><strong>Methods: </strong>We conducted cross-sectional analyses of data collected from the 2018 wave of the Health and Retirement Study. Participants included 1  549 community-dwelling adults aged ≥65 with persistent or recurrent pain (ie, clinically significant pain present at 2 consecutive survey waves).</p><p><strong>Results: </strong>More than one-quarter of older adults with persistent or recurrent pain reported regular alcohol use (≥weekly), nearly half of whom reported hazardous patterns of drinking. Specifically, 32% reported excessive drinking (ie, >2 drinks per day for older men; >1 drink per day for older women), and 22% reported binge drinking (ie, ≥4 drinks on one occasion). Exploratory analyses revealed a high prevalence of hazardous drinking among the subsample of older adults who used opioids (47%).</p><p><strong>Conclusions: </strong>Hazardous alcohol use-including both excessive and binge drinking-is common among older adults with persistent or recurrent pain, including those who take opioids. Given that hazardous drinking can complicate pain management and increase the risk for adverse opioid effects (eg, overdose), the current findings underscore the importance of assessing and addressing hazardous patterns of alcohol use among older adults with persistent or recurrent pain.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10959438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138886856","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":"Exome-Wide Sequencing Study Identified Genetic Variants Associated With Sarcopenic Obesity.","authors":"Qian Xu, Qi-Gang Zhao, Xin-Ling Ma, Shan-Shan Yan, Bai-Xue Han, Zi-Tong Song, Fan Bu, Kuan Li, Lei Zhang, Yu-Fang Pei","doi":"10.1093/gerona/glae025","DOIUrl":"10.1093/gerona/glae025","url":null,"abstract":"<p><p>Sarcopenic obesity (SO) is an age-related disease characterized by the coexistence of excessive adiposity and low muscle mass or function. Although obesity and sarcopenia are heritable conditions, the genetic determinants of SO have not been fully understood. We conducted a large-scale exome-wide association analysis of SO in a sequenced sample of 2 887 cases and 113 284 controls and an imputed sample of 4 003 cases and 161 990 controls in the UK Biobank cohort. Single-variant association analysis identified one locus 1q41 (lead SNP rs1417066, LYPLAL1-AS1, odds ratio [OR] = 1.15, 95% confidence interval [CI] = [1.11-1.19], p = 1.75 × 10-14) that was significantly associated with SO at the exome-wide significance level (p < 1 × 10-8). Colocalization analysis in the Genotype-Tissue Expression expression quantitative trait locus database showed that LYPLAL1-AS1 was colocalized with SO in multiple musculoskeletal-related tissues. Gene-based burden test of rare loss-of-function variants identified 5 genes at the gene-wise significance level (p < 4.3 × 10-6): PDE3B (OR = 2.48, p = 1.10 × 10-6), MYOZ3 (OR = 25.49, p = 1.41 × 10-7), SLC15A3 (OR = 4.75, p = 6.82 × 10-7), RNF130 (OR = 25.83, p = 4.07 × 10-6), and TNK2 (OR = 4.25, p = 8.75 × 10-8). Overall, our study uncovered the genetic effects of both common and rare variants on SO susceptibility, expanded existing knowledge of the genetic architecture of SO, and improved understanding of the genetic mechanisms underlying SO.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547969","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}