Bettina M Beech, Marino A Bruce, Ankita Siddhanta, Gillian L Marshall, Keith E Whitfield, Roland J Thorpe
Background Loneliness is a biopsychosocial stressor linked to poor health outcomes including dementia. Few studies have focused on this association among men and even fewer have examined racial disparities in loneliness and cognitive functioning among this group. The purpose of this study was to examine racial differences in the association between loneliness and cognitive functioning among men in the 2016 wave of the Health and Retirement Study (HRS). Methods This cross-sectional study included Black and White men who completed the core questionnaire and the Leave Behind Questionnaire (n=2227). Any cognitive impairment was the primary outcome and was measured by a dichotomous variable derived from a modified version of the Telephone Interview for Cognitive Status. Loneliness was the primary independent variable and was derived from the 3-item UCLA Loneliness Scale. Modified Poisson regression models with robust standard errors were estimated to generate prevalence ratios and corresponding 95% confidence intervals. Results Black men comprised 18.4% of the study sample; however, the proportion of this group with scores indicating cognitive impairment (35.9%) doubled the corresponding percentage of white men (17.6%). Findings from race-stratified modified Poisson regression models indicated that loneliness was associated with a higher prevalence of any cognitive impairment for White men (PR=1.24, CI:1.05-1.47), but not for Black men (PR=0.92, CI:0.73-1.16). Conclusions Our results underscore the complexity of race when investigating the association between loneliness and cognitive impairment among older men. Additional studies are needed to further examine how loneliness may have racially distinct implications for cognitive outcomes among the population.
{"title":"Racial differences in the association between loneliness and cognitive impairment among older Black and White men","authors":"Bettina M Beech, Marino A Bruce, Ankita Siddhanta, Gillian L Marshall, Keith E Whitfield, Roland J Thorpe","doi":"10.1093/gerona/glae227","DOIUrl":"https://doi.org/10.1093/gerona/glae227","url":null,"abstract":"Background Loneliness is a biopsychosocial stressor linked to poor health outcomes including dementia. Few studies have focused on this association among men and even fewer have examined racial disparities in loneliness and cognitive functioning among this group. The purpose of this study was to examine racial differences in the association between loneliness and cognitive functioning among men in the 2016 wave of the Health and Retirement Study (HRS). Methods This cross-sectional study included Black and White men who completed the core questionnaire and the Leave Behind Questionnaire (n=2227). Any cognitive impairment was the primary outcome and was measured by a dichotomous variable derived from a modified version of the Telephone Interview for Cognitive Status. Loneliness was the primary independent variable and was derived from the 3-item UCLA Loneliness Scale. Modified Poisson regression models with robust standard errors were estimated to generate prevalence ratios and corresponding 95% confidence intervals. Results Black men comprised 18.4% of the study sample; however, the proportion of this group with scores indicating cognitive impairment (35.9%) doubled the corresponding percentage of white men (17.6%). Findings from race-stratified modified Poisson regression models indicated that loneliness was associated with a higher prevalence of any cognitive impairment for White men (PR=1.24, CI:1.05-1.47), but not for Black men (PR=0.92, CI:0.73-1.16). Conclusions Our results underscore the complexity of race when investigating the association between loneliness and cognitive impairment among older men. Additional studies are needed to further examine how loneliness may have racially distinct implications for cognitive outcomes among the population.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233515","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}
Meghan A Cupp, Sarah D Berry, Kaleen N Hayes, Lori A Daiello, Darae Ko, Melissa R Riester, Andrew R Zullo
Background Prescribing cholinesterase inhibitors (ChEIs) concurrently with beta-blockers might cause syncope that increases the risk of fall-related injuries (FRIs). This self-controlled case series study assesses the risk of FRIs associated with initiating ChEIs while receiving beta-blockers among Medicare fee-for-service-insured nursing home (NH) residents in the United States. Methods We identified individuals at their first dispensing of a beta-blocker between 2016 and 2019 after at least 45 days of long-stay NH residency. Individuals were followed from the first day of beta-blocker use until beta-blocker discontinuation, Medicare disenrollment, death, or study end. ChEI initiation was classified as the first 60 days of new ChEI dispensing after 45 days of no ChEI exposure. FRIs were assessed during beta-blocker use periods and age-adjusted incidence rate ratios (IRR) for ChEI-initiation days versus other days were calculated using conditional Poisson regression models. Analyses were weighted for event-dependent observation periods due to the high risk of mortality after an FRI in this population. Subgroup analyses were conducted for several key time-fixed variables, including sex, age, ChEI type, ChEI dose, beta-blocker selectivity and beta-blocker dose. Results The FRI risk after ChEI initiation was not elevated among 837 residents who experienced an FRI while using beta-blockers (IRR=0.90 [95%CLs 0.71, 1.15]). Analyses of ChEI initiation in several subgroups yielded similar results. Conclusions There was no substantial difference in FRI risk when initiating ChEIs among older NH residents receiving beta-blocker therapy versus periods without ChEI initiation, suggesting that there is no clinically significant pharmacodynamic drug-drug interaction between beta-blockers and ChEIs.
{"title":"Cholinesterase Inhibitor Initiation Does Not Increase the Risk of Fall-Related Injury in Older Adults Treated with Beta-blockers: a self-controlled case series design","authors":"Meghan A Cupp, Sarah D Berry, Kaleen N Hayes, Lori A Daiello, Darae Ko, Melissa R Riester, Andrew R Zullo","doi":"10.1093/gerona/glae219","DOIUrl":"https://doi.org/10.1093/gerona/glae219","url":null,"abstract":"Background Prescribing cholinesterase inhibitors (ChEIs) concurrently with beta-blockers might cause syncope that increases the risk of fall-related injuries (FRIs). This self-controlled case series study assesses the risk of FRIs associated with initiating ChEIs while receiving beta-blockers among Medicare fee-for-service-insured nursing home (NH) residents in the United States. Methods We identified individuals at their first dispensing of a beta-blocker between 2016 and 2019 after at least 45 days of long-stay NH residency. Individuals were followed from the first day of beta-blocker use until beta-blocker discontinuation, Medicare disenrollment, death, or study end. ChEI initiation was classified as the first 60 days of new ChEI dispensing after 45 days of no ChEI exposure. FRIs were assessed during beta-blocker use periods and age-adjusted incidence rate ratios (IRR) for ChEI-initiation days versus other days were calculated using conditional Poisson regression models. Analyses were weighted for event-dependent observation periods due to the high risk of mortality after an FRI in this population. Subgroup analyses were conducted for several key time-fixed variables, including sex, age, ChEI type, ChEI dose, beta-blocker selectivity and beta-blocker dose. Results The FRI risk after ChEI initiation was not elevated among 837 residents who experienced an FRI while using beta-blockers (IRR=0.90 [95%CLs 0.71, 1.15]). Analyses of ChEI initiation in several subgroups yielded similar results. Conclusions There was no substantial difference in FRI risk when initiating ChEIs among older NH residents receiving beta-blocker therapy versus periods without ChEI initiation, suggesting that there is no clinically significant pharmacodynamic drug-drug interaction between beta-blockers and ChEIs.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100706","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}
Numerous studies have indicated a close association between gut microbiota dysbiosis, inflammation, and cognitive impairment, highlighting their crucial role in the aging process. 2-(3,4-Dihydroxyphenyl)ethyl 3-hydroxybutanoate (HTHB), a novel derivative of hydroxytryrosol (HT), known for its metabolic and anti-inflammatory properties, was investigated for its effects on memory, inflammation, and gut microbiota in senescence-accelerated mouse prone 8 (SAMP8) mice. The study employed behavioral testing, biochemical detection and 16S RNA analysis. Results revealed that HTHB mitigated memory decline and lymphocyte aberrance, reduced inflammation in the brain cortex, intestine and peripheral system, and modulated gut microbiota dysbiosis. Interestingly, the cognitive function and serum inflammation of mice significantly correlated with differences in gut microbiota in SAMP8 mice. Furthermore, HTHB treatment exhibited an enhancement of gut barrier integrity in colon tissue in SAMP8 mice. In vitro experiments using HCT116 and DLD1 cells further evidenced that HTHB rescued the tight junction protein levels impaired by lipopolysaccharide (LPS). These finding demonstrate that HTHB effectively ameliorates cognitive dysfunction in aged mice, might by modulating gut microbiota, suppressing inflammation and promoting intestinal barrier integrity. This highlights the potential of HTHB as a therapeutic agent for age-related cognitive loss.
{"title":"2-(3,4-dihydroxyphenyl)ethyl 3-hydroxybutanoate (HTHB) ameliorates cognitive dysfunction via modulating gut microbiota in aged senescence-accelerated mouse prone 8 (SAMP8) mice","authors":"Le Shi, Peipei Gao, Yue Zhang, Quanyu Liu, Ranrui Hu, Zhuang Zhao, Yachong Hu, Xiaohong Xu, Yehua Shen, Jiankang Liu, Jiangang Long","doi":"10.1093/gerona/glae220","DOIUrl":"https://doi.org/10.1093/gerona/glae220","url":null,"abstract":"Numerous studies have indicated a close association between gut microbiota dysbiosis, inflammation, and cognitive impairment, highlighting their crucial role in the aging process. 2-(3,4-Dihydroxyphenyl)ethyl 3-hydroxybutanoate (HTHB), a novel derivative of hydroxytryrosol (HT), known for its metabolic and anti-inflammatory properties, was investigated for its effects on memory, inflammation, and gut microbiota in senescence-accelerated mouse prone 8 (SAMP8) mice. The study employed behavioral testing, biochemical detection and 16S RNA analysis. Results revealed that HTHB mitigated memory decline and lymphocyte aberrance, reduced inflammation in the brain cortex, intestine and peripheral system, and modulated gut microbiota dysbiosis. Interestingly, the cognitive function and serum inflammation of mice significantly correlated with differences in gut microbiota in SAMP8 mice. Furthermore, HTHB treatment exhibited an enhancement of gut barrier integrity in colon tissue in SAMP8 mice. In vitro experiments using HCT116 and DLD1 cells further evidenced that HTHB rescued the tight junction protein levels impaired by lipopolysaccharide (LPS). These finding demonstrate that HTHB effectively ameliorates cognitive dysfunction in aged mice, might by modulating gut microbiota, suppressing inflammation and promoting intestinal barrier integrity. This highlights the potential of HTHB as a therapeutic agent for age-related cognitive loss.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100707","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}
Caterina Rosano, Lana M Chahine, Emma L Gay, Paul M Coen, Nico I Bohnen, Stephanie A Studenski, Brian LoPresti, Andrea L Rosso, Theodore Huppert, Anne B Newman, Sarah K Royse, Stephen B Kritchevsky, Nancy W Glynn
Background Fatigability in community-dwelling older adults is highly prevalent and disabling, but lacks a treatment. Greater nigrostriatal dopaminergic signaling can ameliorate performance fatigability in healthy young adults, but its role in community-dwelling older adults is not known. We hypothesized that higher nigrostriatal dopaminergic integrity would be associated with lower performance fatigability, independent of cardiopulmonary and musculoskeletal energetics and other health conditions. Methods In 125 older adults participating in the Study of Muscle, Mobility and Aging, performance fatigability was measured as performance deterioration during a fast 400 meter walk (% slowing down from the 2nd to the 9th lap). Nigrostriatal DA integrity was measured using (+)-[11C] dihydrotetrabenazine (DTBZ) PET imaging. The binding signal was obtained separately for the subregions regulating sensorimotor (posterior putamen), reward (ventral striatum) and executive control processes (dorsal striatum). Multivariable linear regression models of performance fatigability (dependent variable) estimated the coefficients of dopamine integrity in striatal subregions, adjusted for demographics, comorbidities, and cognition. Models were further adjusted for skeletal muscle energetics (via biopsy) and cardiopulmonary fitness (via cardiopulmonary exercise testing). Results Higher [11C]-DTBZ binding in the posterior putamen was significantly associated with lower performance fatigability (demographic-adjusted standardized Beta = -1.08, 95% CI: -1.96, -0.20); results remained independent of adjustment for other covariates, including cardiopulmonary and musculoskeletal energetics. Associations with other striatal subregions were not significant. Discussion Dopaminergic integrity in the sensorimotor striatum may influence performance fatigability in older adults without clinically overt diseases, independent of other aging systems.
背景 在社区居住的老年人中，疲劳是一种非常普遍的致残性疾病，但却缺乏治疗方法。增强黑质多巴胺能信号传导可改善健康年轻人的疲劳表现，但其在社区居住的老年人中的作用尚不清楚。我们假设，较高的黑质多巴胺能完整性与较低的运动疲劳相关，而与心肺和肌肉骨骼能量及其他健康状况无关。方法 在 125 名参加 "肌肉、活动能力与衰老研究"（Study of Muscle, Mobility and Aging）的老年人中，以 400 米快走过程中的表现衰退（从第 2 圈到第 9 圈的减速百分比）来衡量表现疲劳性。黑质纹状体 DA 的完整性是通过 (+)-[11C] 二氢四苄嗪（DTBZ）PET 成像测量的。分别获得了调节感觉运动（后部丘脑）、奖赏（腹侧纹状体）和执行控制过程（背侧纹状体）的亚区域的结合信号。疲劳表现（因变量）的多变量线性回归模型估计了纹状体亚区的多巴胺完整性系数，并对人口统计学、合并症和认知能力进行了调整。根据骨骼肌能量（通过活检）和心肺功能（通过心肺运动测试）对模型进行了进一步调整。结果 后部普塔门中较高的[11C]-DTBZ结合率与较低的表现疲劳度显著相关（人口统计学调整后的标准化贝塔=-1.08，95% CI：-1.96，-0.20）；结果与其他协变量（包括心肺和肌肉骨骼能量）的调整无关。与其他纹状体亚区的相关性不显著。讨论 感觉运动纹状体中多巴胺能的完整性可能会影响无明显临床疾病的老年人的疲劳表现，与其他衰老系统无关。
{"title":"Higher striatal dopamine is related with lower physical performance fatigability in community-dwelling older adults","authors":"Caterina Rosano, Lana M Chahine, Emma L Gay, Paul M Coen, Nico I Bohnen, Stephanie A Studenski, Brian LoPresti, Andrea L Rosso, Theodore Huppert, Anne B Newman, Sarah K Royse, Stephen B Kritchevsky, Nancy W Glynn","doi":"10.1093/gerona/glae209","DOIUrl":"https://doi.org/10.1093/gerona/glae209","url":null,"abstract":"Background Fatigability in community-dwelling older adults is highly prevalent and disabling, but lacks a treatment. Greater nigrostriatal dopaminergic signaling can ameliorate performance fatigability in healthy young adults, but its role in community-dwelling older adults is not known. We hypothesized that higher nigrostriatal dopaminergic integrity would be associated with lower performance fatigability, independent of cardiopulmonary and musculoskeletal energetics and other health conditions. Methods In 125 older adults participating in the Study of Muscle, Mobility and Aging, performance fatigability was measured as performance deterioration during a fast 400 meter walk (% slowing down from the 2nd to the 9th lap). Nigrostriatal DA integrity was measured using (+)-[11C] dihydrotetrabenazine (DTBZ) PET imaging. The binding signal was obtained separately for the subregions regulating sensorimotor (posterior putamen), reward (ventral striatum) and executive control processes (dorsal striatum). Multivariable linear regression models of performance fatigability (dependent variable) estimated the coefficients of dopamine integrity in striatal subregions, adjusted for demographics, comorbidities, and cognition. Models were further adjusted for skeletal muscle energetics (via biopsy) and cardiopulmonary fitness (via cardiopulmonary exercise testing). Results Higher [11C]-DTBZ binding in the posterior putamen was significantly associated with lower performance fatigability (demographic-adjusted standardized Beta = -1.08, 95% CI: -1.96, -0.20); results remained independent of adjustment for other covariates, including cardiopulmonary and musculoskeletal energetics. Associations with other striatal subregions were not significant. Discussion Dopaminergic integrity in the sensorimotor striatum may influence performance fatigability in older adults without clinically overt diseases, independent of other aging systems.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100756","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}
Chunrong Lu, Xiaojun Wang, Pengpeng Ye, Zhilong Lu, Jie Ma, Weifei Luo, Shuai Wang, Xiaochun Chen
Antimicrobial peptides (AMPs) offer a potential solution to the antibiotic crisis owing to their antimicrobial properties, and the human gut biome may be a source of these peptides. However, the potential AMPs and antimicrobial peptide resistance genes (AMPRGs) of gut microbes in different age groups has not been thoroughly assessed. Here, we investigated the potential development of AMPs and the distribution pattern of AMPRGs in the gut microbiome at different ages by analyzing the intestinal metagenomic data of healthy individuals at different life stages (CG: centenarians group n=20; OAG: older adults group n=15; YG: young group n=15). Age-related increases were observed in the potential AMPs within the gut microbiome, with centenarians showing a greater diversity of these peptides. However, the gut microbiome of the CG group had a lower level of AMPRGs compared to that of the OAG group, and it was similar to the level found in the YG group. Additionally, conventional probiotic strains showed a significant positive correlation with certain potential AMPs and were associated with a lower detection of resistance genes. Additionally, comparing potential AMPs with existing libraries revealed limited similarity, indicating that current machine-learning models can identify novel peptides in the gut microbiota. These results indicate that longevity may benefit from diversity of AMPs and lower resistance genes. Our findings help explain the age advantage of the centenarians and identify the potential for antimicrobial peptide biosynthesis in the human gut microbiome, offering insights into the development of antimicrobial peptide resistance and the screening of probiotic strains.
{"title":"Antimicrobial peptides from the gut microbiome of the centenarians: diversification of biosynthesis and youthful development of resistance genes","authors":"Chunrong Lu, Xiaojun Wang, Pengpeng Ye, Zhilong Lu, Jie Ma, Weifei Luo, Shuai Wang, Xiaochun Chen","doi":"10.1093/gerona/glae218","DOIUrl":"https://doi.org/10.1093/gerona/glae218","url":null,"abstract":"Antimicrobial peptides (AMPs) offer a potential solution to the antibiotic crisis owing to their antimicrobial properties, and the human gut biome may be a source of these peptides. However, the potential AMPs and antimicrobial peptide resistance genes (AMPRGs) of gut microbes in different age groups has not been thoroughly assessed. Here, we investigated the potential development of AMPs and the distribution pattern of AMPRGs in the gut microbiome at different ages by analyzing the intestinal metagenomic data of healthy individuals at different life stages (CG: centenarians group n=20; OAG: older adults group n=15; YG: young group n=15). Age-related increases were observed in the potential AMPs within the gut microbiome, with centenarians showing a greater diversity of these peptides. However, the gut microbiome of the CG group had a lower level of AMPRGs compared to that of the OAG group, and it was similar to the level found in the YG group. Additionally, conventional probiotic strains showed a significant positive correlation with certain potential AMPs and were associated with a lower detection of resistance genes. Additionally, comparing potential AMPs with existing libraries revealed limited similarity, indicating that current machine-learning models can identify novel peptides in the gut microbiota. These results indicate that longevity may benefit from diversity of AMPs and lower resistance genes. Our findings help explain the age advantage of the centenarians and identify the potential for antimicrobial peptide biosynthesis in the human gut microbiome, offering insights into the development of antimicrobial peptide resistance and the screening of probiotic strains.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100757","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}
Zengyi Wan, Lori B Chibnik, Linda Valeri, Timothy M Hughes, Deborah Blacker, Yuan Ma
The association between cardiometabolic risk factors and cognitive function has been well documented, but the underlying mechanisms are not fully understood. This longitudinal study aimed to investigate the potential mediating role of DNA methylation in this association. We conducted the analyses in 3708 participants (mean [SD] age: 67.3 [9.49], women: 57.9%) from the Health and Retirement Study who were assessed in the 2014 to 2020 waves, had Infinium Methylation EPIC BeadChip methylation assays from the 2016 Venous Blood Study, and had cognitive assessment between 2016-2020. Causal mediation analyses were used to test the mediation role of DNA methylation in the associations between cardiometabolic risk factors and cognition, adjusting for demographic, socioeconomic, and lifestyle factors. Hypertension (-0.061 in composite cognitive z-score; 95% CI: (-0.119, -0.004)) and diabetes (-0.134; 95% CI: (-0.198, -0.071)) were significantly associated with worse cognitive function while abnormal BMI and hypercholesterolemia were not. An increased number of cardiometabolic risk factors was associated with worse cognitive function (P=0.002). DNA methylation significantly mediated the association of hypertension (mediated effect on composite cognitive z-score: -0.023; 95% CI: (-0.033, -0.014)), diabetes (-0.022; 95% CI: (-0.032, -0.014)), and obesity (-0.021; 95% CI: (-0.033, -0.011)) with cognitive function, while the mediation effect was not observed for having hypercholesterolemia. The estimated proportions mediated were 37.4% for hypertension and 16.7% for diabetes. DNA methylation may be an important mediator linking cardiometabolic risk factors to worse cognition and might even provide a potential target for dementia prevention.
{"title":"DNA Methylation Mediates the Association between Cardiometabolic Risk Factors and Cognition: Findings from the Health and Retirement Study","authors":"Zengyi Wan, Lori B Chibnik, Linda Valeri, Timothy M Hughes, Deborah Blacker, Yuan Ma","doi":"10.1093/gerona/glae167","DOIUrl":"https://doi.org/10.1093/gerona/glae167","url":null,"abstract":"The association between cardiometabolic risk factors and cognitive function has been well documented, but the underlying mechanisms are not fully understood. This longitudinal study aimed to investigate the potential mediating role of DNA methylation in this association. We conducted the analyses in 3708 participants (mean [SD] age: 67.3 [9.49], women: 57.9%) from the Health and Retirement Study who were assessed in the 2014 to 2020 waves, had Infinium Methylation EPIC BeadChip methylation assays from the 2016 Venous Blood Study, and had cognitive assessment between 2016-2020. Causal mediation analyses were used to test the mediation role of DNA methylation in the associations between cardiometabolic risk factors and cognition, adjusting for demographic, socioeconomic, and lifestyle factors. Hypertension (-0.061 in composite cognitive z-score; 95% CI: (-0.119, -0.004)) and diabetes (-0.134; 95% CI: (-0.198, -0.071)) were significantly associated with worse cognitive function while abnormal BMI and hypercholesterolemia were not. An increased number of cardiometabolic risk factors was associated with worse cognitive function (P=0.002). DNA methylation significantly mediated the association of hypertension (mediated effect on composite cognitive z-score: -0.023; 95% CI: (-0.033, -0.014)), diabetes (-0.022; 95% CI: (-0.032, -0.014)), and obesity (-0.021; 95% CI: (-0.033, -0.011)) with cognitive function, while the mediation effect was not observed for having hypercholesterolemia. The estimated proportions mediated were 37.4% for hypertension and 16.7% for diabetes. DNA methylation may be an important mediator linking cardiometabolic risk factors to worse cognition and might even provide a potential target for dementia prevention.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462675","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}
Janie Corley, Alison Pattie, G David Batty, Simon R Cox, Ian J Deary
Background Longevity, a hallmark of successful ageing, is a multifactorial trait with influences from birth onwards. However, limited evidence exists on the pathways linking diverse life-course exposures to longevity, especially within a single cohort. Methods We investigated associations between life-course factors and longevity among community-dwelling adults aged 79 (N=547) from the Lothian Birth Cohort 1921 with a mortality follow-up of 24 years. Cox proportional hazards and structural equation (path) models were used to explore how factors from early-life (social class, childhood IQ, education), mid-life (social class), later-life (health, lifestyle, psychosocial well-being), as well as sex, personality and APOE e4 status, influence survival time in days. Results During follow-up (1999-2023), 538 participants (98%) died (mean age of death=89.3 years) and 9 survived (mean age=101.6 years). Factors associated with lower mortality risk in the multivariable Cox model were higher cognitive function (HR=0.72; 95% CI:0.59-0.88), better physical function (HR=0.61; 95% CI:0.44-0.85), and greater physical activity (HR=0.81; 95% CI 0.71-0.92), while history of cancer was associated with higher mortality risk (HR=1.84; 95% CI:1.22-2.77). The life-course path model identified the same direct predictors, with additional contributions from female sex and non-smoking status, to greater longevity. Early- and mid-life factors (IQ, education, social class), and emotional stability, conscientiousness, and female sex, were indirectly and positively associated with survival trajectories via multiple dimensions of adult health. Conclusions In understanding why people live to very old ages it is necessary to consider factors from throughout the life course, and to include demographic, psychosocial, and health variables.
{"title":"Life-course pathways to exceptional longevity: Evidence from the Lothian Birth Cohort of 1921","authors":"Janie Corley, Alison Pattie, G David Batty, Simon R Cox, Ian J Deary","doi":"10.1093/gerona/glae166","DOIUrl":"https://doi.org/10.1093/gerona/glae166","url":null,"abstract":"Background Longevity, a hallmark of successful ageing, is a multifactorial trait with influences from birth onwards. However, limited evidence exists on the pathways linking diverse life-course exposures to longevity, especially within a single cohort. Methods We investigated associations between life-course factors and longevity among community-dwelling adults aged 79 (N=547) from the Lothian Birth Cohort 1921 with a mortality follow-up of 24 years. Cox proportional hazards and structural equation (path) models were used to explore how factors from early-life (social class, childhood IQ, education), mid-life (social class), later-life (health, lifestyle, psychosocial well-being), as well as sex, personality and APOE e4 status, influence survival time in days. Results During follow-up (1999-2023), 538 participants (98%) died (mean age of death=89.3 years) and 9 survived (mean age=101.6 years). Factors associated with lower mortality risk in the multivariable Cox model were higher cognitive function (HR=0.72; 95% CI:0.59-0.88), better physical function (HR=0.61; 95% CI:0.44-0.85), and greater physical activity (HR=0.81; 95% CI 0.71-0.92), while history of cancer was associated with higher mortality risk (HR=1.84; 95% CI:1.22-2.77). The life-course path model identified the same direct predictors, with additional contributions from female sex and non-smoking status, to greater longevity. Early- and mid-life factors (IQ, education, social class), and emotional stability, conscientiousness, and female sex, were indirectly and positively associated with survival trajectories via multiple dimensions of adult health. Conclusions In understanding why people live to very old ages it is necessary to consider factors from throughout the life course, and to include demographic, psychosocial, and health variables.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462696","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}
Laura Corveleyn, Payel Sen, Peter Adams, Simone Sidoli
Epigenetic changes have been established to be a hallmark of aging, which implies that aging science requires collaborating with the field of chromatin biology. DNA methylation patterns, changes in relative abundance of histone post-translational modifications (PTMs), and chromatin remodeling are the central players in modifying chromatin structure. Aging is commonly associated with an overall increase in chromatin instability, loss of homeostasis and decondensation. However, numerous publications have highlighted that the link between aging and chromatin changes is not nearly as linear as previously expected. This complex interplay of these epigenetics elements during the lifetime of an organism likely contribute to cellular senescence, genomic instability, and disease susceptibility. Yet, the causal links between these phenomena still need to be fully unraveled. In this perspective article, we discuss potential future directions of aging chromatin biology.
{"title":"Linking Aging to Cancer: The Role of Chromatin Biology","authors":"Laura Corveleyn, Payel Sen, Peter Adams, Simone Sidoli","doi":"10.1093/gerona/glae133","DOIUrl":"https://doi.org/10.1093/gerona/glae133","url":null,"abstract":"Epigenetic changes have been established to be a hallmark of aging, which implies that aging science requires collaborating with the field of chromatin biology. DNA methylation patterns, changes in relative abundance of histone post-translational modifications (PTMs), and chromatin remodeling are the central players in modifying chromatin structure. Aging is commonly associated with an overall increase in chromatin instability, loss of homeostasis and decondensation. However, numerous publications have highlighted that the link between aging and chromatin changes is not nearly as linear as previously expected. This complex interplay of these epigenetics elements during the lifetime of an organism likely contribute to cellular senescence, genomic instability, and disease susceptibility. Yet, the causal links between these phenomena still need to be fully unraveled. In this perspective article, we discuss potential future directions of aging chromatin biology.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954669","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}
Megan Hetherington-Rauth, Eileen Johnson, Eugenia Migliavacca, Lisa Langsetmo, Russell T Hepple, Terence E Ryan, Luigi Ferrucci, Denis Breuillé, John Corthesy, Nancy E Lane, Jérôme N Feige, Nicola Napoli, Flavia Tramontana, Eric S Orwoll, Peggy M Cawthon
Tryptophan (TRP) metabolites along the kynurenine (KYN) pathway (KP) have been found to influence muscle. Pro-inflammatory cytokines are known to stimulate the degradation of TRP down the KP. Given that both inflammation and KP metabolites have been connected with loss of muscle, we assessed the potential mediating role of KP metabolites on inflammation and muscle mass in older men. 505 men (85.0±4.2yrs) from the Osteoporotic Fractures in Men cohort study with measured D3-creatine dilution (D3Cr) muscle mass, KP metabolites, and inflammation markers (C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and a subsample (n=305) with interleukin (IL-6, IL-1β, IL-17A) and tumor necrosis factor-α (TNF-α)) were included in the analysis. KP metabolites and inflammatory markers were measured using liquid chromatography-tandem mass spectrometry and immunoassays, respectively. 23-92% of the inverse relationship between inflammatory markers and D3Cr muscle mass was mediated by KP metabolites (indirect effect p<0.05). 3-hydroxyanthranilic acid (3-HAA), quinolinic acid (QA), TRP, xanthurenic acid (XA), KYN/TRP, 3-hydroxykynurenine (3-HK)/3-HAA, QA/3-HAA, and nicotinamide (NAM)/QA mediated the AGP relationship. 3-HAA, QA, KYN/TRP, 3-HK/XA, HKr ratio, 3-HK/3-HAA, QA/3-HAA, and NAM/QA mediated the CRP. KYN/TRP, 3-HK/XA, and NAM/QA explained the relationship for IL-6 and 3-HK/XA and QA/3-HAA for TNF-α. No mediation effect was observed for the other cytokines (indirect effect p>0.05). KP metabolites, particularly higher ratios of KYN/TRP, 3-HK/XA, 3-HK/3-HAA, QA/3-HAA and a lower ratio of NAM/QA, mediated the relationship between inflammation and low muscle mass. Our preliminary cross-sectional data suggest that interventions to alter D3Cr muscle mass may focus on KP metabolites rather than inflammation per se.
{"title":"The mediating role of kynurenine pathway metabolites on the relationship between inflammation and muscle mass in oldest-old men","authors":"Megan Hetherington-Rauth, Eileen Johnson, Eugenia Migliavacca, Lisa Langsetmo, Russell T Hepple, Terence E Ryan, Luigi Ferrucci, Denis Breuillé, John Corthesy, Nancy E Lane, Jérôme N Feige, Nicola Napoli, Flavia Tramontana, Eric S Orwoll, Peggy M Cawthon","doi":"10.1093/gerona/glae131","DOIUrl":"https://doi.org/10.1093/gerona/glae131","url":null,"abstract":"Tryptophan (TRP) metabolites along the kynurenine (KYN) pathway (KP) have been found to influence muscle. Pro-inflammatory cytokines are known to stimulate the degradation of TRP down the KP. Given that both inflammation and KP metabolites have been connected with loss of muscle, we assessed the potential mediating role of KP metabolites on inflammation and muscle mass in older men. 505 men (85.0±4.2yrs) from the Osteoporotic Fractures in Men cohort study with measured D3-creatine dilution (D3Cr) muscle mass, KP metabolites, and inflammation markers (C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and a subsample (n=305) with interleukin (IL-6, IL-1β, IL-17A) and tumor necrosis factor-α (TNF-α)) were included in the analysis. KP metabolites and inflammatory markers were measured using liquid chromatography-tandem mass spectrometry and immunoassays, respectively. 23-92% of the inverse relationship between inflammatory markers and D3Cr muscle mass was mediated by KP metabolites (indirect effect p&lt;0.05). 3-hydroxyanthranilic acid (3-HAA), quinolinic acid (QA), TRP, xanthurenic acid (XA), KYN/TRP, 3-hydroxykynurenine (3-HK)/3-HAA, QA/3-HAA, and nicotinamide (NAM)/QA mediated the AGP relationship. 3-HAA, QA, KYN/TRP, 3-HK/XA, HKr ratio, 3-HK/3-HAA, QA/3-HAA, and NAM/QA mediated the CRP. KYN/TRP, 3-HK/XA, and NAM/QA explained the relationship for IL-6 and 3-HK/XA and QA/3-HAA for TNF-α. No mediation effect was observed for the other cytokines (indirect effect p&gt;0.05). KP metabolites, particularly higher ratios of KYN/TRP, 3-HK/XA, 3-HK/3-HAA, QA/3-HAA and a lower ratio of NAM/QA, mediated the relationship between inflammation and low muscle mass. Our preliminary cross-sectional data suggest that interventions to alter D3Cr muscle mass may focus on KP metabolites rather than inflammation per se.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"127 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954639","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}
intricate relationship between lower extremity muscle strength, area, specific force, and lower urinary tract symptoms (LUTS) in
下肢肌肉力量、面积、比力和下尿路症状（LUTS）之间的复杂关系
{"title":"Commentaries on “Associations of Lower Extremity Muscle Strength, Area, and Specific Force With Lower Urinary Tract Symptoms in Older Men: The Baltimore Longitudinal Study of Aging”","authors":"Yu-Hsiang Lin, Han-Yu Tsai, Yu-Ting Chen","doi":"10.1093/gerona/glae102","DOIUrl":"https://doi.org/10.1093/gerona/glae102","url":null,"abstract":"intricate relationship between lower extremity muscle strength, area, specific force, and lower urinary tract symptoms (LUTS) in","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"22 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140965130","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}
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