Hansen Jenna L, Carroll Judith E, Seeman Teresa E, Cole Steve W, Rentscher Kelly E
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Norman Cousins Center for Psychoneuroimmunology, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, USA.
Brain Behav Immun. 2025 Jan;123:1159-1168. doi: 10.1016/j.bbi.2024.10.022. Epub 2024 Oct 22.
Psychosocial stress and adversity have been linked to accelerated aging and increased risk for age-related diseases. Animal and in vitro studies have shown that exposure to stress hormones (catecholamines, glucocorticoids) can impact biological aging processes such as DNA damage and cellular senescence, suggesting they play a key role in links between stress and aging; however, these associations have not been well investigated in humans. We examined cross-sectional associations between chronic stress exposures, stress hormones, and biological aging markers in midlife adults and whether stress hormones mediated associations between stress and aging. Participants were 531 adults aged 26-78 years (M = 53.9, 50.1% female) in the nationally representative Midlife in the United States Refresher cohort. They reported chronic stress exposures in childhood and adulthood (Stressful Life Event Inventory) and provided 12-hour urine samples used to assess norepinephrine, epinephrine, and cortisol. RNA sequencing of peripheral blood mononuclear cells derived aging biomarkers: the DNA damage response (DDR; 30-gene composite), cellular senescence signal p16 (CDKN2A), and the pro-inflammatory senescence-associated secretory phenotype (SASP; 57-gene composite). Regression models adjusting for age, sex, race/ethnicity, BMI, smoking status, alcohol use, and medications revealed that more childhood exposures were associated with higher norepinephrine (β = 0.09, p = 0.04), independent from adult exposures. Higher norepinephrine was associated with elevated DDR expression (β = 0.17, p < 0.001). Higher norepinephrine (β = 0.14, p = 0.003) and epinephrine (β = 0.10, p = 0.02) were both associated with elevated SASP expression. Statistical mediation analyses implicated elevated norepinephrine as a plausible mediator of associations between childhood exposures and both DDR (unstandardized b = 0.005, 95% CI [0.0002, 0.011]) and SASP (b = 0.002, 95% CI [0.0001, 0.05]). Findings provide preliminary evidence in humans that stress hormones may impact key biological aging processes and may be a mechanism linking chronic stress exposures in childhood to accelerated aging later in life.
心理社会压力和逆境与加速衰老以及患老年相关疾病的风险增加有关。动物和体外研究表明，暴露于应激激素（儿茶酚胺、糖皮质激素）会影响生物衰老过程，如DNA损伤和细胞衰老，这表明它们在压力与衰老之间的联系中起关键作用；然而，这些关联在人类中尚未得到充分研究。我们研究了中年成年人慢性应激暴露、应激激素和生物衰老标志物之间的横断面关联，以及应激激素是否介导了压力与衰老之间的关联。参与者是来自具有全国代表性的美国中年更新队列中的531名年龄在26 - 78岁之间的成年人（M = 53.9，50.1%为女性）。他们报告了童年和成年时期的慢性应激暴露（应激生活事件量表），并提供了用于评估去甲肾上腺素、肾上腺素和皮质醇的12小时尿液样本。对外周血单核细胞进行RNA测序得出衰老生物标志物：DNA损伤反应（DDR；30基因组合）、细胞衰老信号p16（CDKN2A）以及促炎衰老相关分泌表型（SASP；57基因组合）。对年龄、性别、种族/民族、体重指数、吸烟状况、饮酒情况和药物进行调整的回归模型显示，更多的童年暴露与更高的去甲肾上腺素水平相关（β = 0.09，p = 0.04），独立于成年暴露。更高的去甲肾上腺素水平与DDR表达升高相关（β = 0.17，p < 0.001）。更高的去甲肾上腺素水平（β = 0.14，p = 0.
