Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Health Behavior Health Education, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
J Gerontol A Biol Sci Med Sci. 2023 Jul 8;78(7):1092-1099. doi: 10.1093/gerona/glad092.
Psychosocial risk factors have been linked with accelerated epigenetic aging, but little is known about whether psychosocial resilience factors (eg, Sense of Purpose in Life) might reduce epigenetic age acceleration. In this study, we tested if older adults who experience high levels of Purpose might show reduced epigenetic age acceleration. We evaluated the relationship between Purpose and epigenetic age acceleration as measured by 13 DNA methylation (DNAm) "epigenetic clocks" assessed in 1 572 older adults from the Health and Retirement Study (mean age 70 years). We quantified the total association between Purpose and DNAm age acceleration as well as the extent to which that total association might be attributable to demographic factors, chronic disease, other psychosocial variables (eg, positive affect), and health-related behaviors (heavy drinking, smoking, physical activity, and body mass index [BMI]). Purpose in Life was associated with reduced epigenetic age acceleration across 4 "second-generation" DNAm clocks optimized for predicting health and longevity (false discovery rate [FDR] q < 0.0001: PhenoAge, GrimAge, Zhang epigenetic mortality index; FDR q < 0.05: DunedinPoAm). These associations were independent of demographic and psychosocial factors, but substantially attenuated after adjusting for health-related behaviors (drinking, smoking, physical activity, and BMI). Purpose showed no significant association with 9 "first-generation" DNAm epigenetic clocks trained on chronological age. Older adults with greater Purpose in Life show "younger" DNAm epigenetic age acceleration. These results may be due in part to associated differences in health-related behaviors. Results suggest new opportunities to reduce biological age acceleration by enhancing Purpose and its behavioral sequelae in late adulthood.
心理社会风险因素与加速的表观遗传衰老有关，但人们对心理社会弹性因素（例如生活意义感）是否可能降低表观遗传年龄加速知之甚少。在这项研究中，我们测试了经历高水平生活意义感的老年人是否可能表现出较低的表观遗传年龄加速。我们评估了目的与通过 13 个 DNA 甲基化（DNAm）“表观遗传时钟”评估的 1572 名来自健康与退休研究（平均年龄 70 岁）的老年人的表观遗传年龄加速之间的关系。我们量化了目的与 DNAm 年龄加速之间的总关联，以及该总关联归因于人口统计学因素、慢性疾病、其他心理社会变量（例如积极情绪）和与健康相关的行为（大量饮酒、吸烟、身体活动和体重指数 [BMI]）的程度。生活意义感与四种“第二代”DNAm 时钟（专门用于预测健康和长寿的时钟）所衡量的表观遗传年龄加速呈负相关，这些时钟经过优化，可预测健康和长寿（错误发现率 [FDR] q<0.0001：PhenoAge、GrimAge、Zhang 表观遗传死亡率指数；FDR q<0.05：DunedinPoAm）。这些关联独立于人口统计学和心理社会因素，但在调整与健康相关的行为（饮酒、吸烟、身体活动和 BMI）后显著减弱。目的与 9 个基于年龄的 DNAm 表观遗传时钟没有显著关联。生活意义感较强的老年人表现出“更年轻”的 DNAm 表观遗传年龄加速。这些结果可能部分归因于与健康相关的行为的差异。结果表明，通过在晚年增强目的及其行为后果，为降低生物年龄加速提供了新的机会。
