Epigenetic aging mediates the association between life course socioeconomic status and decrements in kidney function across a decade

Agus Surachman; Meera N Harhay; Rose Ann DiMaria-Ghalili; Anthony S Zannas; David M Almeida; Christopher L Coe

doi:10.1007/s11357-025-01728-0

Epigenetic aging mediates the association between life course socioeconomic status and decrements in kidney function across a decade

Geroscience. 2025 Jun 12. doi: 10.1007/s11357-025-01728-0. Online ahead of print.

Authors

Agus Surachman^{1

2}, Meera N Harhay^{3

4}, Rose Ann DiMaria-Ghalili⁵, Anthony S Zannas⁶, David M Almeida^{7

8}, Christopher L Coe⁹

Affiliations

¹ Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, 3215 Market St, Rm 552, Philadelphia, PA, 19104, USA. as5796@drexel.edu.
² College of Nursing and Health Professions, Drexel University, Philadelphia, PA, USA. as5796@drexel.edu.
³ Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, 3215 Market St, Rm 552, Philadelphia, PA, 19104, USA.
⁴ Department of Medicine, College of Medicine, Drexel University, Philadelphia, PA, USA.
⁵ College of Nursing and Health Professions, Drexel University, Philadelphia, PA, USA.
⁶ Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁷ Department of Human Development and Family Studies, College of Health and Human Development, The Pennsylvania State University, University Park, PA, USA.
⁸ Center for Healthy Aging, The Pennsylvania State University, University Park, PA, USA.
⁹ Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.

PMID: 40500519
DOI: 10.1007/s11357-025-01728-0

Abstract

Epigenetic aging measures are novel molecular indicators of biological aging that predict age-related chronic disease. We examined whether several established indices of epigenetic aging mediated the association between life course socioeconomic status (SES) and decrements in kidney function across a decade. Biomarker data were from 252 non-Hispanic (NH) Black and white participants who had consented to genetic analyses in Wave 2 (2004-2009) and 3 (2014-2021) of the Midlife in the United States study (MIDUS). Life course SES included parental education, a proxy of early life SES, and a composite score of adult SES based on the highest education level, household income to poverty line ratio, health insurance coverage, perception of the availability of money to meet needs, and difficulty level paying monthly bills. We included five measures of epigenetic age accelerations (EAA), based on the residuals after each epigenetic clock was regressed on chronological age (Horvath, Horvath blood and skin, Hannum, PhenoAge, and GrimAge) and one measure of the pace of aging (DunedinPACE) obtained during MIDUS 2. Kidney function was based on serum creatinine-based estimated glomerular filtration rate (eGFR), calculated using the CKD-EPI formula (without race adjustment). We calculated absolute decrements in eGFR across 11 years between MIDUS waves 2 and 3. Analyses were adjusted for age, sex, and health-related covariates (currently smoking, obese, hypertension, and insulin resistance). Lower adult SES and accelerated epigenetic aging, especially accelerated GrimAge and faster DunedinPACE pace of aging, mediated the association between lower parental education and larger decrements in eGFR. Accelerated epigenetic aging is associated with larger decrements in kidney function across a decade and may be one of the critical explanatory pathways for the higher burden of chronic kidney disease (CKD) among lower SES individuals.

Keywords: EGFR; Epigenetic aging; Geroscience; Renal aging; Socioeconomic status.

Abstract

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