加速衰老介导了不健康生活方式与心血管疾病、癌症和死亡的关联。
Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality.
机构信息
Center for Clinical Big Data and Analytics Second Affiliated Hospital, and Department of Big Data in Health Science School of Public Health, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.
Department of Community Medicine and Health Care, Connecticut Convergence Institute for Translation in Regenerative Engineering, Institute for Systems Genomics, University of Connecticut Health, Farmington, Connecticut, USA.
出版信息
J Am Geriatr Soc. 2024 Jan;72(1):181-193. doi: 10.1111/jgs.18611. Epub 2023 Oct 4.
BACKGROUND
With two well-validated aging measures capturing mortality and morbidity risk, this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes.
METHODS
Data were from 405,944 adults (40-69 years) from UK Biobank (UKB) and 9972 adults (20-84 years) from the US National Health and Nutrition Examination Survey (NHANES). An unhealthy lifestyles score (range: 0-5) was constructed based on five factors (smoking, drinking, physical inactivity, unhealthy body mass index, and unhealthy diet). Two aging measures, Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel) were calculated using nine and seven blood biomarkers, respectively, with a higher value indicating the acceleration of aging. The outcomes included incident cardiovascular disease (CVD), incident cancer, and all-cause mortality in UKB; CVD mortality, cancer mortality, and all-cause mortality in NHANES. A general linear regression model, Cox proportional hazards model, and formal mediation analysis were performed.
RESULTS
The unhealthy lifestyles score was positively associated with PhenoAgeAccel (UKB: β = 0.741; NHANES: β = 0.874, all p < 0.001). We further confirmed the respective associations of PhenoAgeAccel and unhealthy lifestyles with the outcomes in UKB and NHANES. The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident CVD, incident cancer, and all-cause mortality were 20.0%, 17.8%, and 26.6% (all p < 0.001) in UKB, respectively. Similar results were found in NHANES. The findings were robust when using another aging measure-BioAgeAccel.
CONCLUSIONS
Accelerated aging partially mediated the associations of lifestyles with CVD, cancer, and mortality in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late life beyond lifestyle interventions.
背景
本研究采用两种经过充分验证的衰老指标来衡量死亡率和发病率风险，旨在探讨生活方式不健康与不良健康结局之间的关联是否以及在何种程度上可以通过衰老来解释。
方法
数据来自英国生物库（UKB）的 405944 名成年人（40-69 岁）和美国国家健康与营养检查调查（NHANES）的 9972 名成年人（20-84 岁）。根据五个因素（吸烟、饮酒、身体活动不足、不健康的体重指数和不健康的饮食）构建了一个生活方式不健康评分（范围：0-5）。使用 9 种血液生物标志物计算表型年龄加速（PhenoAgeAccel），使用 7 种血液生物标志物计算生物年龄加速（BioAgeAccel），得分越高表示衰老加速。结果包括 UKB 的心血管疾病（CVD）发病、癌症发病和全因死亡率；NHANES 的 CVD 死亡率、癌症死亡率和全因死亡率。采用一般线性回归模型、Cox 比例风险模型和正式中介分析进行分析。
结果
生活方式不健康评分与 PhenoAgeAccel 呈正相关（UKB：β=0.741；NHANES：β=0.874，均 P<0.001）。我们进一步证实了 PhenoAgeAccel 以及生活方式与 UKB 和 NHANES 中结局的各自关联。PhenoAgeAccel 在生活方式与 CVD 发病、癌症发病和全因死亡率之间关联中的中介比例分别为 UKB 中的 20.0%、17.8%和 26.6%（均 P<0.001），在 NHANES 中也得到了类似的结果。当使用另一种衰老指标-BioAgeAccel 时，研究结果仍然稳健。
结论
衰老的加速部分解释了生活方式与英国和美国人群 CVD、癌症和死亡率之间的关联。这些发现揭示了一种新的途径，以及在晚年通过抗衰老项目减轻健康不平等的潜力，超越了生活方式干预。
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