エピジェネティックな年齢加速は、早期の人生における逆境や精神疾患に伴う成人期の認知能力低下のバイオマーカーとなる Epigenetic age acceleration as a biomarker for impaired cognitive abilities in adulthood following early life adversity and psychiatric disorders
John M. Felt, Natan Yusupov, Karra D. Harrington, Julia Fietz, Zhenyu “Zach” Zhang, Martin J. Sliwinski, Nilam Ram, Kieran J. O’Donnell, BeCOME Working Group, Michael J. Meaney, Frank W. Putnam, Jennie G. Noll, Elisabeth B. Binder, Chad E. Shenk
Neurobiology of Stress Available online: 15 October 2023
Early life adversity and psychiatric disorders are associated with earlier declines in neurocognitive abilities during adulthood. These declines may be preceded by changes in biological aging, specifically epigenetic age acceleration, providing an opportunity to uncover genome-wide biomarkers that identify individuals most likely to benefit from early screening and prevention.
Five unique epigenetic age acceleration clocks derived from peripheral blood were examined in relation to latent variables of general and speeded cognitive abilities across two independent cohorts: 1) the Female Growth and Development Study (FGDS; n = 86), a 30-year prospective cohort study of substantiated child sexual abuse and non-abused controls, and 2) the Biological Classification of Mental Disorders study (BeCOME; n = 313), an adult community cohort established based on psychiatric disorders.
A faster pace of biological aging (DunedinPoAm) was associated with lower general cognitive abilities in both cohorts and slower speeded abilities in the BeCOME cohort. Acceleration in the Horvath clock was significantly associated with slower speeded abilities in the BeCOME cohort but not the FGDS. Acceleration in the Hannum clock and the GrimAge clock were not significantly associated with either cognitive ability. Accelerated PhenoAge was associated with slower speeded abilities in the FGDS but not the BeCOME cohort.
The present results suggest that epigenetic age acceleration has the potential to serve as a biomarker for neurocognitive decline in adults with a history of early life adversity or psychiatric disorders. Estimates of epigenetic aging may identify adults at risk of cognitive decline that could benefit from early neurocognitive screening.
小児期の性的虐待に暴露された女性の発達の30年間にわたるコルチゾールの軌跡を前向きに測定: 中年期におけるエピジェネティックな年齢加速による調整 Cortisol trajectories measured prospectively across thirty years of female development following exposure to childhood sexual abuse: Moderation by epigenetic age acceleration at midlife
Chad E. Shenk, John M. Felt, Nilam Ram, Kieran J. O’Donnell, Martin J. Sliwinski, Irina Pokhvisneva, Lizbeth Benson, Michael J. Meaney, Frank W. Putnam, Jennie G. Noll
Psychoneuroendocrinology Available online 26 November 2021
Lasting changes in the hypothalamic-pituitary-adrenal (HPA) axis are a potential indication of the biological embedding of early life adversity, yet, prospective and repeatedly collected data are needed to confirm this relation. Likewise, integrating information from multiple biological systems, such as the HPA axis and the epigenome, has the potential to identify individuals with enhanced embedding of early life adversity. The current study reports results from the Female Growth and Development Study, a 30-year prospective cohort study of childhood sexual abuse (CSA). Females exposed to substantiated CSA and a demographically-similar comparison condition were enrolled and resting state cortisol concentrations were sampled on seven subsequent occasions across childhood, adolescence, and adulthood. Differences in participants’ cortisol trajectories were examined in relation to prior CSA exposure and DNA methylation-derived epigenetic age acceleration at midlife. Bilinear spline growth models revealed a trajectory where cortisol secretion increased until approximately age twenty and then declined into mid-life, consistent with normative trends. However, cortisol concentrations peaked at a lower level and transitioned to the decline phase at an earlier age for females in the CSA condition with increased epigenetic age acceleration. Robustness tests across three independent measures of epigenetic age acceleration demonstrated similar results for lower peak cortisol levels and earlier ages at transition. Results suggest that CSA is associated with significant changes in HPA-axis activity over extended periods of time with these changes most pronounced in females with accelerated epigenetic aging in mid-life. Implications for biological embedding models of early life adversity and adulthood health are discussed.