# Epigenetics of Successful Aging

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $716,716

## Abstract

Project Abstract
Numerous studies have documented a role for inherited genetic variation in common chronic diseases, their
risk factors and overall longevity. However, the distributions and incidence rates of these same conditions
have changed dramatically during modern times (1946-2014); a shift too dramatic in too short of a period to be
affected by evolutionary pressures leading to changes in allele frequencies. Rather, this shift is most likely
accounted for by changes in health care and lifestyle, which, in turn, have led to increased longevity and
opening the door to successful aging. Lifestyle changes and aging itself can lead to alterations in the action of
relevant genes via epigenetic modification of the DNA. This proposed research will test the hypotheses
that signatures of DNA methylation measured in the blood of middle-aged adults are associated with
successful aging patterns later in life (Aim 1); that these signatures persist in old age (Aim 2); and
these signatures are associated with subsequent differences in the expression level of relevant genes
(Aim 3). Replication opportunities have been identified and are an integral part of the workscope. We will focus
on the overall construct of successful aging (i.e., physical, cognitive and functional well-being) instead of any
one disease entity or risk factor for both scientific (i.e., pleiotropy) and practical (impact on quality of life)
reasons. We will use the Level II definition of successful aging proposed and validated by McLaughlin et al in
the Health and Retirement Study. The Atherosclerosis Risk in Communities (ARIC) Study, a biracial
longitudinal cohort study of the development of atherosclerosis and its risk factors, has collected and stored
biosamples at each of its previous five examinations, and measured blood biomarkers and DNA sequence
variation in successful searches for predictors of disease risk. This proposed ancillary study will support
measurement of epigenetic patterns associated with successful aging. The following specific aims will be
pursued: 1) To identify signatures of DNA methylation measured in the blood of middle-aged adults that are
associated with successful aging status later in life; 2) To determine whether DNA methylation signatures of
successful aging established in middle age among 1,800 ARIC participants from Aim 1 persist ~21 years later
when they reach old age; 3) To examine whether the DNA methylation status of the genes identified in middle
age (Aim 1) is correlated with gene expression in old age. The long-term goal of the proposed project is that by
increasing our understanding of the biological determinants and trajectory of successful aging, this study may
help to inform public health interventions focused on modifiable risk factors and the development of new
therapeutic agents that will make successful aging an attainable goal for a greater number of individuals in the
population.

## Key facts

- **NIH application ID:** 9843558
- **Project number:** 5R01HL131136-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** ERIC A. BOERWINKLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $716,716
- **Award type:** 5
- **Project period:** 2016-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843558

## Citation

> US National Institutes of Health, RePORTER application 9843558, Epigenetics of Successful Aging (5R01HL131136-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9843558. Licensed CC0.

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