Aging
Life-course Adversity and Biological Aging in the Hispanic Community Health Study / Study of Latinos: A Life-course Model Analysis Yinxian Chen* Yinxian Chen Sarina Abrishamcar Krista Perreira Maria Argos Andrea Baccarelli Jianwen Cai Christian Dye Maria M. Llabre Linda C. Gallo Martha Daviglus Bharat Thyagarajan Carmen R. Isasi Karen N. Conneely Timothy L. Lash Anke Huels Shakira F. Suglia
The effect of adversity on aging may vary over the lifespan. Assessing the associations among life-course adversity (LA), biological aging, and the relevant life-course model may reveal mechanisms of LA in aging and inform prevention. We included 970 individuals with DNA methylation profiles at Visit 2 (2014-2017) from the Hispanic Community Health Study/Study of Latinos to calculate GrimAge epigenetic age and DunedinPACE pace of aging. The LA was defined as the weighted sum of exposure to childhood (CA) and adulthood adversity (AA), which were assessed at Visit 1 (2008-2011) as a sum of physical and sexual abuse, material hardship, and substance abuse of someone close (scored 0-4). The Bayesian relevant life-course model (BRLM) was used to estimate the association between LA and epigenetic aging, examining three hypothetical life-course models: critical period (Weight[W]CA=1/WAA=1), sensitivity period (WCA>WAA / WCA<WAA), and accumulation (WCA=WAA) model. We further examined the pathway model by causal mediation analysis of the indirect effect of CA through AA. After addressing confounders, one unit increase in LA was associated with a 0.86-year increase in GrimAge acceleration (AgeAccelGrim) (95% credible interval [CrI]: 0.25, 1.45) and 0.017-year/calendar year in DunedinPACE (95%CrI: 0.000, 0.036). WCA was 25% (95% CrI: 1%, 71%) and WAA 75% (95%CrI: 29%, 99%) for AgeAccelGrim, while WCA 48% (95% CrI: 4%, 96%) and WAA 52% (95% CrI: 4%, 96%) for DunedinPACE. We found an indirect effect of CA through AA (0.13 years, 95%CI: 0.03, 0.24) on AgeAccelGrim but not DunedinPACE. For AgeAccelGrim, BRLM identified the sensitive period model as the most relevant, but mediation analysis supported the pathway model. For DunedinPACE, the accumulation model best explained the life-course association. The varied importance of CA and AA by aging markers suggests that LA may have distinct pathways affecting different aging outcomes and should be explored.
