From the Department of Epidemiology (Suglia), Rollins School of Public Health, Emory University, Atlanta, Georgia; School of Global Integrative Studies (Clausing) and Center for Brain, Biology, and Behavior (Clausing), University of Nebraska-Lincoln, Lincoln, Nebraska; Department of Sociomedical Sciences (Shelton), Mailman School of Public Health, New York, New York; Department of Human Genetics (Conneely, Baccarelli), School of Medicine, Emory University, Atlanta, Georgia; Department of Environmental Health (Prada-Ortega), Mailman School of Public Health, New York, New York; Department of Epidemiology (DeVivo), Harvard T. H. Chan School of Public Health; Channing Division of Network Medicine (DeVivo), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Epidemiology (Factor-Litvak), Mailman School of Public Health, New York, New York; Child Health and Development Studies (Cirillo, Cohn), Public Health Institute, Berkeley; and Department of Sociology (Link), University of California Riverside, Riverside, California.
Psychosom Med. 2024 Apr 1;86(3):137-145. doi: 10.1097/PSY.0000000000001284. Epub 2024 Jan 10.
Psychosocial stressors have been linked with accelerated biological aging in adults; however, few studies have examined stressors across the life course in relation to biological aging.
In 359 individuals (57% White, 34% Black) from the Child Health and Development Studies Disparities study, economic (income, education, financial strain), social (parent-child relations, caretaker responsibilities) and traumatic (death of a sibling or child, violence exposure) stressors were assessed at multiple time points (birth and ages 9, 15, and 50 years). Experiences of major discrimination were assessed at age 50. Life period stress scores were then assessed as childhood (birth-age 15 years) and adulthood (age 50 years). At age 50 years, participants provided blood samples, and DNA methylation was assessed with the EPIC BeadChip. Epigenetic age was estimated using six epigenetic clocks (Horvath, Hannum, Skin and Blood age, PhenoAge, GrimAge, Dunedin Pace of Aging). Age acceleration was determined using residuals from regressing chronologic age on each of the epigenetic age metrics. Telomere length was assessed using the quantitative polymerase chain reaction-based methods.
In linear regression models adjusted for race and gender, total life stress, and childhood and adult stress independently predicted accelerated aging based on GrimAge and faster pace of aging based on the DunedinPace. Associations were attenuated after adjusting for smoking status. In sex-stratified analyses, greater childhood stress was associated with accelerated epigenetic aging among women but not men. No associations were noted with telomere length.
We found that cumulative stressors across the life course were associated with accelerated epigenetic age, with differences by sex (e.g., accelerated among women). Further research of this association in large and diverse samples is needed.
心理社会压力源与成年人的生物衰老加速有关；然而，很少有研究考察整个生命过程中的压力源与生物衰老的关系。
在儿童健康与发展研究差异研究中的 359 名个体（57%为白人，34%为黑人）中，在多个时间点（出生时和 9 岁、15 岁和 50 岁时）评估了经济（收入、教育、经济紧张）、社会（亲子关系、照顾者责任）和创伤性（兄弟姐妹或孩子死亡、暴力暴露）压力源。在 50 岁时评估了主要歧视经历。然后评估了生活时期压力得分，包括儿童期（出生至 15 岁）和成年期（50 岁）。在 50 岁时，参与者提供了血液样本，并使用 EPIC BeadChip 评估了 DNA 甲基化。使用六个表观遗传时钟（Horvath、Hannum、皮肤和血液年龄、PhenoAge、GrimAge、Dunedin 衰老速度）估计表观遗传年龄。通过从每个表观遗传年龄指标回归到年龄来确定年龄加速。使用基于定量聚合酶链反应的方法评估端粒长度。
在调整种族和性别后进行线性回归模型中，总生活压力以及儿童期和成年期压力独立预测了基于 GrimAge 的加速衰老和基于 DunedinPace 的更快衰老速度。在调整吸烟状况后，关联减弱。在性别分层分析中，较大的儿童期压力与女性而非男性的加速表观遗传衰老有关。与端粒长度没有关联。
我们发现，整个生命过程中的累积压力源与加速的表观遗传年龄有关，性别差异（例如，女性加速）。需要在大型和多样化的样本中进一步研究这种关联。
