Epigenetic clocks as mediators of health behaviors and mortality in middle-aged and older adults

IF 4 3区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Nutrition Health & Aging Pub Date : 2025-06-11 DOI:10.1016/j.jnha.2025.100602

Xing-Ling Chen , Qiang-Qiang Zhao , Sheng-Rong Lin , Xing-Ling He , Xiao-Jiao Zhang , Si-Jing Li , Zi-Ru Li , Jia-Hui Chen , Hua Zhang , Xiao-Fang Li , Yue-Hui Zhou , Hui-Li Liao , Shu-Ning Sun , Zhong-Qi Yang , Shi-Hao Ni , Lu Lu

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引用次数: 0

Abstract

Background

The impact of healthy lifestyles on epigenetic age acceleration (EAA) and mortality in middle-aged/ senior populations remains unclear. This study investigates associations between lifestyle factors, EAA biomarkers, and mortality risk.

Method

The 2532 adults of 50 years or older that registered in NHANES between 1999–2002.This study evaluated compares first- to third-generation epigenetic clocks (HannumAge, HorvathAge, PhenoAge, GrimAge2, DunedinPoAm) in predicting mortality risk associations between five lifestyle domains (diet, abdominal adiposity, physical activity, smoking, alcohol) and EAA were analyzed via multivariable regression, with mediation models testing EAA’s role in lifestyle-mortality relationships.

Results

Survival curves results identified DunedinPoAm, GrimAge2AA, and PhenoAgeAA as robust biomarkers of accelerated biological aging, independent of chronological age. In multivariable linear regression models, full adherence to healthy behaviors reduced GrimAge2AA by β = −5.55 years, PhenoAgeAA by β = −2.64 years, and DunedinPoAm by β = −0.06 SD, with smoking cessation demonstrating the strongest GrimAge2AA attenuation (10.17 years). Stratified analyses revealed pronounced benefits: cancer patients adhering to healthy diets (β = −0.04 SD, P for interaction = 0.01) and hypertensive individuals reducing smoking (β = −0.05 SD, P for interaction = 0.04) showed significant EAA mitigation. The sensitivity analysis is consistent with the original results. Mediation analyses indicated GrimAge2AA accounted for 63.58% of lifestyle-survival associations, DunedinPoAm (44.63%) and PhenoAgeAA (28.45%).

Conclusions

These findings suggest that comprehensive adherence to healthy lifestyle behaviors is associated with reduced epigenetic aging, supporting their potential utility as targets for mortality risk mitigation. And emphasize the utility of epigenetic clocks in precision gerontology.

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表观遗传时钟在中老年健康行为和死亡率中的调节作用

健康生活方式对中老年人群表观遗传年龄加速（EAA）和死亡率的影响尚不清楚。本研究调查了生活方式因素、EAA生物标志物和死亡风险之间的关系。方法1999-2002年间在NHANES登记的2532名50岁及以上的成年人。本研究比较了第一代和第三代表观遗传时钟（HannumAge, HorvathAge, PhenoAge, GrimAge2, DunedinPoAm）在预测五种生活方式领域（饮食，腹部肥胖，体育活动，吸烟，酒精）和EAA之间的死亡风险相关性，并通过多变量回归分析，使用中介模型测试EAA在生活方式-死亡率关系中的作用。结果生存曲线结果确定DunedinPoAm、GrimAge2AA和PhenoAgeAA是独立于实足年龄的加速生物衰老的强有力的生物标志物。在多变量线性回归模型中，完全坚持健康行为使GrimAge2AA降低β = - 5.55年，使PhenoAgeAA降低β = - 2.64年，使DunedinPoAm降低β = - 0.06 SD，其中戒烟使GrimAge2AA衰减最强（10.17年）。分层分析显示了显著的益处：癌症患者坚持健康饮食（β = - 0.04 SD，相互作用P = 0.01）和高血压患者减少吸烟（β = - 0.05 SD，相互作用P = 0.04）显示了显著的EAA缓解。敏感性分析与原始结果一致。调解分析显示，GrimAge2AA占生活方式生存关联的63.58%，DunedinPoAm占44.63%，PhenoAgeAA占28.45%。结论：这些发现表明，全面坚持健康的生活方式行为与减少表观遗传衰老有关，支持其作为降低死亡风险目标的潜在效用。并强调表观遗传时钟在精确老年学中的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Nutrition Health & Aging 医学-老年医学

CiteScore

7.80

自引率

3.40%

发文量

136

审稿时长

4-8 weeks

期刊介绍： There is increasing scientific and clinical interest in the interactions of nutrition and health as part of the aging process. This interest is due to the important role that nutrition plays throughout the life span. This role affects the growth and development of the body during childhood, affects the risk of acute and chronic diseases, the maintenance of physiological processes and the biological process of aging. A major aim of "The Journal of Nutrition, Health & Aging" is to contribute to the improvement of knowledge regarding the relationships between nutrition and the aging process from birth to old age.