Jenna L Hansen, Judith E Carroll, Teresa E Seeman, Steve W Cole, Kelly E Rentscher
{"title":"终生慢性压力暴露、压力荷尔蒙和生物衰老:美国中年(MIDUS)研究结果。","authors":"Jenna L Hansen, Judith E Carroll, Teresa E Seeman, Steve W Cole, Kelly E Rentscher","doi":"10.1016/j.bbi.2024.10.022","DOIUrl":null,"url":null,"abstract":"<p><p>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<sub>age</sub> = 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<sup>INK4a</sup> (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.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":""},"PeriodicalIF":8.8000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lifetime chronic stress Exposures, stress Hormones, and biological Aging: Results from the midlife in the United States (MIDUS) study.\",\"authors\":\"Jenna L Hansen, Judith E Carroll, Teresa E Seeman, Steve W Cole, Kelly E Rentscher\",\"doi\":\"10.1016/j.bbi.2024.10.022\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sub>age</sub> = 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<sup>INK4a</sup> (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.</p>\",\"PeriodicalId\":9199,\"journal\":{\"name\":\"Brain, Behavior, and Immunity\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":8.8000,\"publicationDate\":\"2024-10-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain, Behavior, and Immunity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.bbi.2024.10.022\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain, Behavior, and Immunity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.bbi.2024.10.022","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Lifetime chronic stress Exposures, stress Hormones, and biological Aging: Results from the midlife in the United States (MIDUS) study.
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 (Mage = 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 p16INK4a (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.
期刊介绍:
Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals.
As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.