Journals of Gerontology Series A-Biological Sciences and Medical Sciences最新文献

{"title":"Causal Roles of Lifestyle, Psychosocial Characteristics, and Sleep Status in Sarcopenia: A Mendelian Randomization Study.","authors":"Mingchong Liu, Daqian Yu, Yutao Pan, Shengchao Ji, Ning Han, Chensong Yang, Guixin Sun","doi":"10.1093/gerona/glad191","DOIUrl":"10.1093/gerona/glad191","url":null,"abstract":"<p><strong>Background: </strong>Many studies reported that lifestyle, psychosocial characteristics, and sleep status related to sarcopenia, although few studies provided evidence of causal relationships between them.</p><p><strong>Methods: </strong>The data used in our study were from UK Biobank, FinnGen Release 8, and large genome-wide association study meta-analyses. Two-sample Mendelian randomization was conducted to identify the causal associations of 21 traits of lifestyle, psychosocial characteristics, and sleep status with 6 traits of sarcopenia. Benjamini-Hochberg correction was performed to reduce the bias caused by multiple tests. Risk factor analyses were performed to explore the potential mechanism behind the exposures.</p><p><strong>Results: </strong>Mendelian randomization analyses after adjustment proved the causal roles of coffee intake, education years, smoking, leisure screen time, and moderate-to-vigorous intensity physical activity during leisure time in sarcopenia was proven although providing no significant evidence for causal roles for carbohydrates intake, protein intake, alcohol, and sleep status in sarcopenia.</p><p><strong>Conclusions: </strong>Our results strongly support that coffee intake, education years, smoking, leisure screen time, and moderate-to-vigorous intensity physical activity during leisure time played significantly causal roles in sarcopenia, which may provide new intervention strategies for preventing the development of sarcopenia.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10325925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Terminal Decline in Physical Function in Older Adults.","authors":"Erwin Stolz, Hannes Mayerl, Graciela Muniz-Terrera, Thomas M Gill","doi":"10.1093/gerona/glad119","DOIUrl":"10.1093/gerona/glad119","url":null,"abstract":"<p><strong>Background: </strong>It is currently unclear whether (and when) physical function exhibits a terminal decline phase, that is, a substantial acceleration of decline in the very last years before death.</p><p><strong>Methods: </strong>702 deceased adults aged 70 years and older from the Yale PEP Study provided 4 133 measurements of physical function (Short Physical Performance Battery, SPPB) up to 20 years before death. In addition, continuous gait and chair rise subtest scores (in seconds) were assessed. Generalized mixed regression models with random change points were used to estimate the onset and the steepness of terminal decline in physical function.</p><p><strong>Results: </strong>Decline accelerated in the last years of life in all 3 measures of physical function. The onset of terminal decline occurred 1 year before death for the SPPB, and at 2.5 and 2.6 years before death for chair rise and gait speed test scores, respectively. Terminal declines in physical function were 6-8 times steeper than pre-terminal declines. Relative to those whose condition leading to death was frailty, participants who died from dementia and cancer had an up to 6 months earlier and 3 months later onset of terminal decline in SPPB, respectively.</p><p><strong>Conclusions: </strong>Terminal decline in physical function among older adults is comparable to the more established terminal decline phenomenon in cognition. Our results provide additional evidence of late-life rapid decline in physical function due to impending death.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9767851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Network Efficiency Predicts Conversion to Incident Parkinsonism in Patients With Cerebral Small Vessel Disease.","authors":"Mengfei Cai, Mina A Jacob, José Marques, David G Norris, Marco Duering, Rianne A J Esselink, Yuhu Zhang, Frank-Erik de Leeuw, Anil M Tuladhar","doi":"10.1093/gerona/glad182","DOIUrl":"10.1093/gerona/glad182","url":null,"abstract":"<p><strong>Background: </strong>To investigate whether structural network disconnectivity is associated with parkinsonian signs and their progression, as well as with an increased risk of incident parkinsonism.</p><p><strong>Methods: </strong>In a prospective cohort (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort study) consisting of 293 participants with small vessel disease (SVD), we assessed parkinsonian signs and incident parkinsonism over an 8-year follow-up. In addition, we reconstructed the white matter network followed by graph-theoretical analyses to compute the network metrics. Conventional magnetic resonance imaging markers for SVD were assessed.</p><p><strong>Results: </strong>We included 293 patients free of parkinsonism at baseline (2011), with a mean age 68.8 (standard deviation [SD] 8.4) years, and 130 (44.4%) were men. Nineteen participants (6.5%) developed parkinsonism during a median (SD) follow-up time of 8.3 years. Compared with participants without parkinsonism, those with all-cause parkinsonism had higher Unified Parkinson's Disease Rating scale (UPDRS) scores and lower global efficiency at baseline. Baseline global efficiency was associated with UPDRS motor scores in 2011 (β = -0.047, p < .001) and 2015 (β = -0.84, p < .001), as well as with the changes in UPDRS scores during the 4-year follow-up (β = -0.63, p = .004). In addition, at the regional level, we identified an inter-hemispheric disconnected network associated with an increased UPDRS motor score. Besides, lower global efficiency was associated with an increased risk of all-cause and vascular parkinsonism independent of SVD markers.</p><p><strong>Conclusions: </strong>Our findings suggest that global network efficiency is associated with a gradual decline in motor performance, ultimately leading to incident parkinsonism in the elderly with SVD. Global network efficiency may have the added value to serve as a useful marker to capture changes in motor signs.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9910852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Mild Behavioral Impairment on Longitudinal Changes in Cognition.","authors":"Hillary J Rouse, Zahinoor Ismail, Ross Andel, Victor A Molinari, John A Schinka, Brent J Small","doi":"10.1093/gerona/glad098","DOIUrl":"10.1093/gerona/glad098","url":null,"abstract":"<p><strong>Background: </strong>To examine cross-sectional differences and longitudinal changes in cognitive performance based on the presence of mild behavioral impairment (MBI) among older adults who are cognitively healthy or have mild cognitive impairment (MCI).</p><p><strong>Methods: </strong>Secondary data analysis of participants (n = 17 291) who were cognitively healthy (n = 11 771) or diagnosed with MCI (n = 5 520) from the National Alzheimer's Coordinating Center database. Overall, 24.7% of the sample met the criteria for MBI. Cognition was examined through a neuropsychological battery that assessed attention, episodic memory, executive function, language, visuospatial ability, and processing speed.</p><p><strong>Results: </strong>Older adults with MBI, regardless of whether they were cognitively healthy or diagnosed with MCI, performed significantly worse at baseline on tasks for attention, episodic memory, executive function, language, and processing speed and exhibited greater longitudinal declines on tasks of attention, episodic memory, language, and processing speed. Cognitively healthy older adults with MBI performed significantly worse than those who were cognitively healthy without MBI on tasks of visuospatial ability at baseline and on tasks of processing speed across time. Older adults with MCI and MBI performed significantly worse than those with only MCI on executive function at baseline and visuospatial ability and processing speed tasks across time.</p><p><strong>Conclusions: </strong>This study found evidence that MBI is related to poorer cognitive performance cross-sectionally and longitudinally. Additionally, those with MBI and MCI performed worse across multiple tasks of cognition both cross-sectionally and across time. These results provide support for MBI being uniquely associated with different aspects of cognition.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9289499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Protective Effect of Familial Longevity Persists After Age 100: Findings From the Danish National Registers.","authors":"Angéline Galvin, Jacob Krabbe Pedersen, Mary K Wojczynski, Svetlana Ukraintseva, Konstantin Arbeev, Mary Feitosa, Michael A Province, Kaare Christensen","doi":"10.1093/gerona/glad164","DOIUrl":"10.1093/gerona/glad164","url":null,"abstract":"<p><strong>Background: </strong>A recent study suggested that the protective effect of familial longevity becomes negligible for centenarians. However, the authors assessed the dependence on familial longevity in centenarians by comparing centenarians with 1 parent surviving to age 80+ to centenarians whose same-sexed parent did not survive to age 80. Here we test whether the protective effect of familial longevity persists after age 100 using more restrictive definitions of long-lived families.</p><p><strong>Methods: </strong>Long-lived sibships were identified through 3 nationwide, consecutive studies in Denmark, including families with either at least 2 siblings aged 90+ or a Family Longevity Selection Score (FLoSS) above 7. Long-lived siblings enrolled in these studies and who reached age 100 were included. For each sibling, 5 controls matched on sex and year of birth were randomly selected among centenarians in the Danish population. Survival time from age 100 was described with Kaplan-Meier curves for siblings and controls separately. Survival analyses were performed using stratified Cox proportional hazards models.</p><p><strong>Results: </strong>A total of 340 individuals from long-lived sibships who survived to age 100 and 1 700 controls were included. Among the long-lived siblings and controls, 1 650 (81%) were women. The results showed that long-lived siblings presented better overall survival after age 100 than sporadic long-livers (hazard ratio [HR]  = 0.80, 95% confidence interval [CI]  = 0.71-0.91), with even lower estimate (HR = 0.65, 95% CI = 0.50-0.85) if familial longevity was defined by FLoSS.</p><p><strong>Conclusions: </strong>The present study, with virtually no loss to follow-up, demonstrated a persistence of protective effect of familial longevity after age 100.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9778190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Potential Causal Effects of Telomere Length on Health Outcomes: A Phenome-Wide Investigation and Mendelian Randomization Study.","authors":"Wenxiu Wang, Ninghao Huang, Zhenhuang Zhuang, Zimin Song, Yueying Li, Xue Dong, Wendi Xiao, Yimin Zhao, Jinzhu Jia, Zhonghua Liu, Lu Qi, Tao Huang","doi":"10.1093/gerona/glad128","DOIUrl":"10.1093/gerona/glad128","url":null,"abstract":"<p><strong>Background: </strong>Telomere length has been linked to various health outcomes. To comprehensively investigate the causal effects of telomere length throughout the human disease spectrum, we conducted a phenome-wide Mendelian randomization study (MR-PheWAS) and a systematic review of MR studies.</p><p><strong>Methods: </strong>We conducted a PheWAS to screen for associations between telomere length and 1 035 phenotypes in the UK Biobank (n = 408 354). The exposure of interest was the genetic risk score (GRS) of telomere length. Observed associations passing multiple testing corrections were assessed for causality by 2-sample MR analysis. A systematic review of MR studies on telomere length was performed to harmonize the published evidence and complement our findings.</p><p><strong>Results: </strong>Of the 1 035 phenotypes tested, PheWAS identified 29 and 78 associations of telomere length GRS at a Bonferroni- and false discovery rate-corrected threshold; 24 and 66 distinct health outcomes were causal in the following principal MR analysis. The replication MR using data from the FinnGen study provided evidence of causal effects of genetically instrumented telomere length on 28 out of 66 outcomes, including decreased risks of 5 diseases in respiratory diseases, digestive diseases, and myocardial infarction, and increased risks of 23 diseases, mainly comprised neoplasms, diseases of the genitourinary system, and essential hypertension. A systematic review of 53 MR studies found evidence to support 16 out of the 66 outcomes.</p><p><strong>Conclusions: </strong>This large-scale MR-PheWAS identified a wide range of health outcomes that were possibly affected by telomere length, and suggested that susceptibility to telomere length may vary across disease categories.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9846190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Growth Differentiation Factors 11 and 8, Their Antagonists Follistatin and Follistatin-Like-3, and Risk of Heart Failure in Elders.","authors":"Jorge R Kizer, Sheena Patel, Peter Ganz, Anne B Newman, Shalender Bhasin, Se-Jin Lee, Peggy M Cawthon, Nathan K LeBrasseur, Sanjiv J Shah, Bruce M Psaty, Russell P Tracy, Steven R Cummings","doi":"10.1093/gerona/glad206","DOIUrl":"10.1093/gerona/glad206","url":null,"abstract":"<p><strong>Background: </strong>Heterochronic parabiosis has identified growth differentiation factor (GDF)-11 as a potential means of cardiac rejuvenation, but findings have been inconsistent. A major barrier has been lack of assay specificity for GDF-11 and its homolog GDF-8.</p><p><strong>Methods: </strong>We tested the hypothesis that GDF-11 and GDF-8, and their major antagonists follistatin and follistatin-like (FSTL)-3, are associated with incident heart failure (HF) and its subtypes in elders. Based on validation experiments, we used liquid chromatography-tandem mass spectrometry to measure total serum GDF-11 and GDF-8, along with follistatin and FSTL-3 by immunoassay, in 2 longitudinal cohorts of older adults.</p><p><strong>Results: </strong>In 2 599 participants (age 75.2 ± 4.3) followed for 10.8 ± 5.6 years, 721 HF events occurred. After adjustment, neither GDF-11 (HR per doubling: 0.93 [0.67, 1.30]) nor GDF-8 (HR: 1.02 per doubling [0.83, 1.27]) was associated with incident HF or its subtypes. Positive associations with HF were detected for follistatin (HR: 1.15 [1.00, 1.32]) and FLST-3 (HR: 1.38 [1.03, 1.85]), and with HF with preserved ejection fraction for FSTL-3 (HR: 1.77 [1.03, 3.02]). (All HRs per doubling of biomarker.) FSTL-3 associations with HF appeared stronger at higher follistatin levels and vice versa, and also for men, Blacks, and lower kidney function.</p><p><strong>Conclusions: </strong>Among older adults, serum follistatin and FSTL-3, but not GDF-11 or GDF-8, were associated with incident HF. These findings do not support the concept that low serum levels of total GDF-11 or GDF-8 contribute to HF late in life, but do implicate transforming growth factor-β superfamily pathways as potential therapeutic targets.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10538157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical Resilience as a Predictor of Lifespan and Late-Life Health in Genetically Heterogeneous Mice.","authors":"Ashley K Brown, Daniel L Mazula, Lori Roberts, Carolyn Roos, Bin Zhang, Vesselina M Pearsall, Marissa J Schafer, Thomas A White, Runqing Huang, Navasuja Kumar, Jordan D Miller, Richard A Miller, Nathan K LeBrasseur","doi":"10.1093/gerona/glad207","DOIUrl":"10.1093/gerona/glad207","url":null,"abstract":"<p><p>Dynamic measures of resilience-the ability to resist and recover from a challenge-may be informative of the rate of aging before overt manifestations such as chronic disease, disability, and frailty. From this perspective mid-life resilience may predict longevity and late-life health. To test this hypothesis, we developed simple, reproducible, clinically relevant challenges, and outcome measures of physical resilience that revealed differences between and within age groups of genetically heterogeneous mice, and then examined associations between mid-life resilience and both lifespan and late-life measures of physiological function. We demonstrate that time to recovery from isoflurane anesthesia and weight change following a regimen of chemotherapy significantly differed among young, middle-aged, and older mice, and were more variable in older mice. Females that recovered faster than the median time from anesthesia (more resilient) at 12 months of age lived 8% longer than their counterparts, while more resilient males in mid-life exhibited better cardiac (fractional shortening and left ventricular volumes) and metabolic (glucose tolerance) function at 24 months of age. Moreover, female mice with less than the median weight loss at Day 3 of the cisplatin challenge lived 8% longer than those that lost more weight. In contrast, females who had more weight loss between Days 15 and 20 were relatively protected against early death. These data suggest that measures of physical resilience in mid-life may provide information about individual differences in aging, lifespan, and key parameters of late-life health.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10215321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Associations Between Lifestyle Habits and Risk of Benign Prostatic Hyperplasia: A Two-Sample Mendelian Randomization Study.","authors":"Fan Jia, Zhitao Wei, Xiangrui Kong, Yinhui Mao, Yong Yang","doi":"10.1093/gerona/glad187","DOIUrl":"10.1093/gerona/glad187","url":null,"abstract":"<p><strong>Background: </strong>Benign prostatic hyperplasia (BPH) most often occurs in older men; previous studies and clinical experience suggest a potential link between lifestyle habits such as sleep habits, sedentary behavior, exercise levels, and BPH, but whether they have a clear causal relationship and the direction of that causality is unclear. We aimed to investigate the causal relationship between lifestyle habits and BPH using 2-sample Mendelian randomization (MR) analysis.</p><p><strong>Methods: </strong>Instrumental genetic independent variables strongly associated with the selected exposure factors were filtered from published genome-wide association studies (GWAS) consisting primarily of European ancestry samples. GWAS from BPH was analyzed as an MR outcome with the inverse-variance weighted method, maximum likelihood, weighted median method, MR-Egger regression, and several sensitivity analyses, including Cochran's Q test, intercept of MR-Egger, and MR pleiotropy residual sum and outlier test.</p><p><strong>Results: </strong>MR analysis showed a significant causal risk relationship between sleep duration and BPH, with an odds ratio of 0.42 (95% confidence interval, 0.25-0.69, p = .001) for BPH when sleep duration was increased by 1 standard deviation, but we did not find a causal relationship between the 2 when we performed a reverse analysis. However, sedentary behavior and different levels of exercise did not significantly affect the risk of BPH.</p><p><strong>Conclusions: </strong>This study showed a strong causal relationship between sleep levels and BPH, with adequate sleep duration being a protective factor for BPH.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9911819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Level of ATPase Inhibitory Factor 1 and Intrinsic Capacity in Community-Dwelling Older Adults: Prospective Data From the MAPT Study.","authors":"Jaqueline Aragoni da Silva, Laurent O Martinez, Yves Rolland, Souad Najib, Mikaël Croyal, Bertrand Perret, Nabila Jabrane-Ferrat, Hicham El Costa, Sophie Guyonnet, Bruno Vellas, Philipe de Souto Barreto","doi":"10.1093/gerona/glad142","DOIUrl":"10.1093/gerona/glad142","url":null,"abstract":"<p><strong>Background: </strong>Intrinsic capacity (IC) is a concept related to functionality that reflects healthy aging. ATPase inhibitory factor 1 (IF1) is a multifaceted protein that regulates mitochondrial oxidative phosphorylation (OXPHOS), and may be involved in IC. The objective of this study is to investigate the association between plasma levels of IF1 and IC changes in community-dwelling older adults.</p><p><strong>Methods: </strong>Community-dwelling older adults from the Multidomain Alzheimer Preventive Trial (MAPT Study) were enrolled in this study. A composite IC score was calculated based on 4 IC domains: locomotion, psychological dimension, cognition, and vitality (with data available annually over 4 years of follow-up). Secondary analyses were conducted on the sensory domain (with data available only for 1 year of follow-up). Mixed-model linear regression adjusted for confounders was conducted.</p><p><strong>Results: </strong>A total of 1 090 participants with usable IF1 values were included in the study (75.3 ± 4.4 years; 64% females). Compared to the lowest quartile, both the low- and high-intermediate IF1 quartiles were found to be cross-sectionally associated with greater composite IC scores across 4 domains (βlow-intermediate, 1.33; 95% confidence interval [CI] 0.06-2.60 and βhigh-intermediate, 1.78; 95% CI 0.49-3.06). In the secondary analyses, the highest quartile was found to be associated with a slower decline in composite IC scores across 5 domains over 1 year (βhigh 1.60; 95% CI 0.06-3.15). The low- and high-intermediate IF1 quartiles were also found to be cross-sectionally associated with greater locomotion (βlow-intermediate, 2.72; 95% CI 0.36-5.08) and vitality scores (βhigh-intermediate, 1.59; 95% CI 0.06-3.12), respectively.</p><p><strong>Conclusions: </strong>This study is the first to demonstrate that levels of circulating IF1, a mitochondrial-related biomarker, are associated with IC composite scores in both cross-sectional and prospective analyses among community-dwelling older adults. However, further research is needed to confirm these findings and elucidate the potential underlying mechanisms that may explain these associations.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9957116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}