Systematic underestimation of the epigenetic clock and age acceleration in older subjects.
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ABSTRACT:
SUBMITTER: El Khoury LY
PROVIDER: S-EPMC6915902 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Publications
Systematic underestimation of the epigenetic clock and age acceleration in older subjects.
El Khoury Louis Y LY Gorrie-Stone Tyler T Smart Melissa M Hughes Amanda A Bao Yanchun Y Andrayas Alexandria A Burrage Joe J Hannon Eilis E Kumari Meena M Mill Jonathan J Schalkwyk Leonard C LC
Genome biology 20191217 1
<h4>Background</h4>The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate "age acceleration" in various tissues and environments.<h4>Results</h4>The model systematically underestimates age in tissues from older people. This is seen in all examined tissues but most strongly in the cerebellum and is consistently observed in multiple datasets. Age acceleration is thus age-dependent, ...[more]
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Project description:BackgroundEpigenetic age acceleration, a measure of biological aging based on DNA methylation, is associated with cardiovascular mortality. However, little is known about its relationship with hypertensive target organ damage to the heart, kidneys, brain, and peripheral arteries.MethodsWe investigated associations between intrinsic (IEAA) or extrinsic (EEAA) epigenetic age acceleration, blood pressure, and six types of organ damage in a primarily hypertensive cohort of 1390 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. DNA methylation from peripheral blood leukocytes was collected at baseline (1996-2000), and measures of target organ damage were assessed in a follow-up visit (2000-2004). Linear regression with generalized estimating equations was used to test for associations between epigenetic age acceleration and target organ damage, as well as effect modification of epigenetic age by blood pressure or sex. Sequential Oligogenic Linkage Analysis Routines (SOLAR) was used to test for evidence of shared genetic and/or environmental effects between epigenetic age acceleration and organ damage pairs that were significantly associated.ResultsAfter adjustment for sex, chronological age, and time between methylation and organ damage measures, higher IEAA was associated with higher urine albumin to creatinine ratio (UACR, p?=?0.004), relative wall thickness (RWT, p?=?0.022), and left ventricular mass index (LVMI, p?=?0.007), and with lower ankle-brachial index (ABI, p?=?0.014). EEAA was associated with higher LVMI (p?=?0.005). Target organ damage associations for all but IEAA with LVMI remained significant after further adjustment for blood pressure and antihypertensive use (p?<?0.05). Further adjustment for diabetes attenuated the IEAA associations with UACR and RWT, and adjustment for smoking attenuated the IEAA association with ABI. No effect modification by age or sex was observed.ConclusionsMeasures of epigenetic age acceleration may help to better characterize the functional mechanisms underlying organ damage from cellular aging and/or hypertension. These measures may act as subclinical biomarkers for damage to the kidney, heart, and peripheral vasculature; however more research is needed to determine whether these relationships remain independent of lifestyle factors and comorbidities.
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