Xuening Zhang, Hao Zhao, Zilin Li, Xinjie Liu, Yurong Zhang, Ning Yang, Tongchao Zhang, Xiaorong Yang, Ming Lu
{"title":"Accelerated biological aging, healthy behaviors, and genetic susceptibility with incidence of stroke and its subtypes: A prospective cohort study","authors":"Xuening Zhang, Hao Zhao, Zilin Li, Xinjie Liu, Yurong Zhang, Ning Yang, Tongchao Zhang, Xiaorong Yang, Ming Lu","doi":"10.1111/acel.14427","DOIUrl":null,"url":null,"abstract":"<p>Stroke risk increases with chronological age, but the relationship with biological age (BA) acceleration is poorly understood. We aimed to examine the association between BA acceleration and incident stroke and its subtypes, explore the modifying effects on genetic susceptibility, and assess how BA acceleration mediates the effect of behavior score. We studied 253,932 UK Biobank participants and computed two BA measures (Klemera-Doubal Method [KDM], Phenotypic Age [PhenoAge]), with BA acceleration calculated by regressing BA on chronological age. The polygenic risk score (PRS) was derived from 87 genetic loci. The behaviors score was based on diet, physical activity, tobacco/nicotine, sleep, and BMI. During a median follow-up of 13.6 years, 5460 strokes, 4337 ischemic stroke (IS), 951 intracerebral hemorrhage (ICH), and 553 subarachnoid hemorrhage (SAH) cases were documented. Adjusting for confounding factors, each standard deviation increase in BA acceleration was associated with higher stroke risk: for KDM-BA acceleration, stroke (HR = 1.28, 95% CI = 1.25–1.32), IS (1.32, 1.28–1.36), ICH (1.15, 1.08–1.23), and SAH (1.16, 1.07–1.27); for PhenoAge acceleration, stroke (1.22, 1.19–1.25), IS (1.26, 1.22–1.29), ICH (1.08, 1.02–1.16), and SAH (1.08, 1.00–1.18). Compared to participants with the lowest PRS and BA acceleration, those with the highest PRS and BA acceleration had the highest stroke risk (KDM-BA acceleration: 2.19, 1.85–2.59; PhenoAge acceleration: 2.03, 1.69–2.42). Additionally, there was an additive interaction between KDM-BA acceleration and PRS. The mediation proportion of BA acceleration in associations of behaviors score with incident stroke and its subtypes ranged from 15.84% to 33.08%. BA acceleration may raise stroke risk, especially in those with high genetic risk. Maintaining healthy behaviors may help mitigate this risk.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8000,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14427","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging Cell","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/acel.14427","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0
Abstract
Stroke risk increases with chronological age, but the relationship with biological age (BA) acceleration is poorly understood. We aimed to examine the association between BA acceleration and incident stroke and its subtypes, explore the modifying effects on genetic susceptibility, and assess how BA acceleration mediates the effect of behavior score. We studied 253,932 UK Biobank participants and computed two BA measures (Klemera-Doubal Method [KDM], Phenotypic Age [PhenoAge]), with BA acceleration calculated by regressing BA on chronological age. The polygenic risk score (PRS) was derived from 87 genetic loci. The behaviors score was based on diet, physical activity, tobacco/nicotine, sleep, and BMI. During a median follow-up of 13.6 years, 5460 strokes, 4337 ischemic stroke (IS), 951 intracerebral hemorrhage (ICH), and 553 subarachnoid hemorrhage (SAH) cases were documented. Adjusting for confounding factors, each standard deviation increase in BA acceleration was associated with higher stroke risk: for KDM-BA acceleration, stroke (HR = 1.28, 95% CI = 1.25–1.32), IS (1.32, 1.28–1.36), ICH (1.15, 1.08–1.23), and SAH (1.16, 1.07–1.27); for PhenoAge acceleration, stroke (1.22, 1.19–1.25), IS (1.26, 1.22–1.29), ICH (1.08, 1.02–1.16), and SAH (1.08, 1.00–1.18). Compared to participants with the lowest PRS and BA acceleration, those with the highest PRS and BA acceleration had the highest stroke risk (KDM-BA acceleration: 2.19, 1.85–2.59; PhenoAge acceleration: 2.03, 1.69–2.42). Additionally, there was an additive interaction between KDM-BA acceleration and PRS. The mediation proportion of BA acceleration in associations of behaviors score with incident stroke and its subtypes ranged from 15.84% to 33.08%. BA acceleration may raise stroke risk, especially in those with high genetic risk. Maintaining healthy behaviors may help mitigate this risk.
期刊介绍:
Aging Cell, an Open Access journal, delves into fundamental aspects of aging biology. It comprehensively explores geroscience, emphasizing research on the mechanisms underlying the aging process and the connections between aging and age-related diseases.