Analysis of Epigenetic Age Acceleration and Healthy Longevity Among Older US Women

Abstract

IMPORTANCEAccelerated biological aging is associated with decreased physical capability and cognitive functioning, which are associated with increased risk of morbidity and mortality. OBJECTIVE We investigated associations between epigenetic age acceleration (EAA), a biomarker associated with aging, and healthy longevity among older women. DESIGN, SETTING, AND PARTICIPANTS This cohort study was a secondary analysis of participants in the Women's Health Initiative (WHI) who were eligible to survive to age 90 years by September 30, 2020. Participants were located in multiple centers. This study was restricted to women with genome-wide DNA methylation data, generated from baseline blood samples within 3 WHI ancillary studies. Median (IQR) follow-up times from baseline were 21.6 (19.6-22.9) years and 21.4 (19.8-22.7) years for women who survived to age 90 years with and without intact mobility, respectively, and 13.2 (8.8-16.7) for women who did not survive to age 90 years. Data were analyzed from December 2020 to July 2021. EXPOSURES EAA was estimated using 4 established "clocks": Horvath pantissue, Hannum, Pheno, and Grim. MAIN OUTCOMES AND MEASURES Using multinomial logistic regression, odds ratios (ORs) and 95% CIs were estimated for 3 healthy longevity outcomes for each clock: survival to age 90 years with intact mobility, survival to age 90 years without intact mobility, and no survival to age 90 years. RESULTS Among 1813 women, there were 464 women (mean [SD] age at baseline, 71.6 [3.5] years) who survived to age 90 years with intact mobility and cognitive functioning, 420 women (mean [SD] age at baseline, 71.3 [3.2] years) who survived to age 90 years without intact mobility and cognitive functioning, and 929 women (mean [SD] age at baseline, 70.2 [3.4] years) who did not survive to age 90 years. Women who survived to age 90 years with intact mobility and cognitive function were healthier at baseline compared with women who survived without those outcomes or who did not survive to age 90 years (eg, 143 women [30.8%] vs 101 women [24.0%] and 202 women [21.7%]with 0 chronic conditions). The odds of surviving to age 90 years with intact mobility were lower for every 1 SD increase in EAA compared with those who did not survive to age 90 years as measured

Epigenetic clocks derived from western samples differentially reflect Taiwanese health outcomes

“…Given the advancement of epigenetics, several epigenetic clocks have been developed to estimate human biological age, with five especially receiving much attention ( Hannum et al, 2013 ; Horvath 2013 ; Levine et al, 2018 ; Lu et al, 2019 ; Belsky et al, 2022 ). Epigenetic age acceleration (EAA), usually obtained from the residuals of regressing epigenetic age on chronological age, measures whether people are aging faster than their chronological age ( Jain et al, 2022 ; Lo and Lin 2022 ). EAA can provide important insights into human health ( Horvath et al, 2016 ).…”

Grip strength is inversely associated with DNA methylation age acceleration

“…as compared with chronological age). 21 , 22 The objective of this study was to determine the association between grip strength and DNAm age acceleration derived from three epigenetic clocks trained on phenotypic ageing (i.e. age‐related health conditions/profiles) and mortality.…”

“…A number of epigenetic clock measures have been generated for measuring an individual's epigenetic age, and in particular, to indicate accelerated or decelerated biological ageing (i.e. as compared with chronological age) 21,22 . The objective of this study was to determine the association between grip strength and DNAm age acceleration derived from three epigenetic clocks trained on phenotypic ageing (i.e.…”

The lipidomic correlates of epigenetic aging across the adult lifespan: A population‐based study

“…AgeAccelPheno and AgeAccelGrim represent the residual variation in estimated biological age independent of chronological age, indicating whether individuals have biologically aged faster or slower in comparison to their chronological age (Fox et al, 2023). Specifically, an increase in AgeAccelPheno and/or AgeAccelGrim with changing lipid levels is referred to as accelerated biological aging, whereas a decrease in AgeAccelPheno and/or AgeAccelGrim with changing lipid levels is referred to as slower biological aging (Jain et al, 2022;McCrory et al, 2021). The coefficients of variation (CVs) of lipid concentrations were all below 10%.…”