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><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":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14427"},"PeriodicalIF":8.0000,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1111/acel.14427","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL 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.
Aging CellBiochemistry, Genetics and Molecular Biology-Cell Biology
自引率
2.60%
发文量
212
期刊介绍:
Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health.
The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include:
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Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.