Han Laura K M, Aghajani Moji, Penninx Brenda W J H, Copeland William E, Aberg Karolina A, van den Oord Edwin J C G
Department of Psychiatry, Amsterdam UMC, location Vrije Universiteit, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia.
Psychol Med. 2024 Oct 7;54(12):1-9. doi: 10.1017/S0033291724001570.
Cross-sectional studies have identified health risks associated with epigenetic aging. However, it is unclear whether these risks make epigenetic clocks 'tick faster' (i.e. accelerate biological aging). The current study examines concurrent and lagged within-person changes of a variety of health risks associated with epigenetic aging.
Individuals from the Great Smoky Mountains Study were followed from age 9 to 35 years. DNA methylation profiles were assessed from blood, at multiple timepoints (i.e. waves) for each individual. Health risks were psychiatric, lifestyle, and adversity factors. Concurrent ( = 539 individuals; 1029 assessments) and lagged ( = 380 individuals; 760 assessments) analyses were used to determine the link between health risks and epigenetic aging.
Concurrent models showed that BMI ( = 0.15, < 0.01) was significantly correlated to epigenetic aging at the subject-level but not wave-level. Lagged models demonstrated that depressive symptoms ( = 1.67 months per symptom, = 0.02) in adolescence accelerated epigenetic aging in adulthood, also when models were fully adjusted for BMI, smoking, and cannabis and alcohol use.
Within-persons, changes in health risks were unaccompanied by concurrent changes in epigenetic aging, suggesting that it is unlikely for risks to immediately 'accelerate' epigenetic aging. However, time lagged analyses indicated that depressive symptoms in childhood/adolescence predicted epigenetic aging in adulthood. Together, findings suggest that age-related biological embedding of depressive symptoms is not instant but provides prognostic opportunities. Repeated measurements and longer follow-up times are needed to examine stable and dynamic contributions of childhood experiences to epigenetic aging across the lifespan.
横断面研究已经确定了与表观遗传衰老相关的健康风险。然而，尚不清楚这些风险是否会使表观遗传时钟“走得更快”（即加速生物衰老）。本研究考察了与表观遗传衰老相关的多种健康风险的同期和滞后个体内变化。
对来自大烟山研究的个体从9岁追踪至35岁。在多个时间点（即波次）对每个个体的血液进行DNA甲基化谱评估。健康风险包括精神、生活方式和逆境因素。采用同期分析（n = 539名个体；1029次评估）和滞后分析（n = 380名个体；760次评估）来确定健康风险与表观遗传衰老之间的联系。
同期模型显示，在个体水平上，体重指数（β = 0.15，p < 0.01）与表观遗传衰老显著相关，但在波次水平上不相关。滞后模型表明，青少年时期的抑郁症状（每个症状β = 1.67个月，p = 0.02）会加速成年期的表观遗传衰老，即使在模型对体重指数、吸烟、大麻和酒精使用进行完全调整后也是如此。
在个体内部，健康风险的变化并未伴随着表观遗传衰老的同期变化，这表明风险不太可能立即“加速”表观遗传衰老。然而，时间滞后分析表明，儿童期/青少年期的抑郁症状可预测成年期的表观遗传衰老。总之，研究结果表明，抑郁症状与年龄相关的生物嵌入并非即时发生，但提供了预后机会。需要重复测量和更长的随访时间来研究童年经历对整个生命周期表观遗传衰老的稳定和动态影响。
