Patterns of DNA methylation as an indicator of biological aging: State of the science and future directions in precision health promotion

Abstract

Background: A rapidly expanding literature suggests that individuals of the same chronological age show significant variation in biological age.

Purpose: The purpose of this article is to review the literature surrounding epigenetic age as estimated by DNA methylation, involving the addition or removal of methyl groups to DNA that can alter gene expression without changing the DNA sequence.

Methods: This state of the science literature review summarizes current approaches in epigenetic age determination and applications of aging algorithms.

Findings: A number of algorithms estimate epigenetic age using DNA methylation markers, primarily among adults. Algorithm application has focused on determining predictive value for risk of disease and death and identifying antecedents to age acceleration. Several studies have incorporated epigenetic age to evaluate intervention effectiveness.

Discussion: As the research community continues to refine aging algorithms, there may be opportunity to promote health from a precision health perspective.

Keywords: Aging; Epigenomics; Methylation; Nursing; Precision health.

Figure 1.

DNA methylation Chromosomes, found in the nucleus of most living cells, carry the DNA sequence of an organism. The double-stranded DNA sequence forms a double helix, with each DNA strand composed of smaller units termed nucleotides. Nucleotides form base pairs, whereby adenine (A) pairs with thymine (T) and cytosine (C) pairs with guanine (G). As shown in Box A, DNA methylation occurs when a methyl group (CH3) is added to the cytosine of a phosphate-linked cytosine-guanine (CpG) base pair. Removal of methyl groups can be accomplished by the conversion of 5-methylcytosine to 5-hydroxymethylcytosine. As shown in Box B, when CpGs are methylated, gene expression can be repressed. When CpGs are demethylated, gene expression can be enhanced.

Figure 2.

DNA methylation age acceleration and deceleration in disease and deathWhen DNA methylation aging is accelerated (orange line) or decelerated (green line), the biological thresholds for various diseases and all-cause mortality (dashed line) may be reached early or later than chronologically anticipated, respectively.