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Observational Study
. 2023 Jun;12(11):12149-12160.
doi: 10.1002/cam4.5908. Epub 2023 Apr 9.

Accelerated epigenetic aging and myopenia in young adult cancer survivors

Stephanie C Gehle  1 , Daniel Kleissler  2 , Hillary Heiling  3 , Allison Deal  2 , Zongli Xu  4 , Vanessa L Ayer Miller  5 , Jack A Taylor  4 , Andrew B Smitherman  1   2
Affiliations
Observational Study

Accelerated epigenetic aging and myopenia in young adult cancer survivors

Stephanie C Gehle et al. Cancer Med. 2023 Jun.

Abstract

Background: Young adult cancer survivors experience early aging-related morbidities and mortality. Biological aging biomarkers may identify at-risk survivors and increase our understanding of mechanisms underlying this accelerated aging.

Methods: Using an observational study design, we cross-sectionally measured DNA methylation-based epigenetic age in young adult cancer survivors at a tertiary, academic state cancer hospital. Participants were a convenience sample of consecutively enrolled survivors of childhood, adolescent, and young adult cancers treated with either an anthracycline or alkylating agent, and who were at least 3 months post-treatment. Similarly aged healthy comparators were consecutively enrolled. Cancer treatment and treatment intensity were compared to DNA methylation-based epigenetic age and pace of aging.

Results: Sixty survivors (58 completing assessments, mean age 20.5 years, range 18-29) and 27 comparators (mean age 20 years, range 17-29) underwent DNA methylation measurement. Survivors were predominantly female (62%) and white (60%) and averaged nearly 6 years post-treatment (range 0.2-25 years). Both epigenetic age (AgeAccelGrim: 1.5 vs. -2.4, p < 0.0001; AgeAccelPheno 2.3 vs. -3.8, p = 0.0013) and pace of aging (DunedinPACE 0.99 vs. 0.83, p < 0.0001) were greater in survivors versus comparators. In case-case adjusted analysis, compared to survivors with normal muscle mass, myopenic survivors had higher AgeAccelGrim (2.2 years, 95% CI 0.02-4.33, p = 0.02), AgeAccelPheno (6.2 years, 2.36-10.09, p < 0.001), and DunedinPACE (0.11, 0.05-0.17, p < 0.001).

Conclusions: Epigenetic age is older and pace of aging is faster in young adult cancer survivors compared to noncancer peers, which is evident in the early post-therapy period. Survivors with physiological impairment demonstrate greater epigenetic age advancement. Measures of epigenetic age may identify young adult survivors at higher risk for poor functional and health outcomes.

Keywords: DNA methylation; aging; cancer survivorship; epigenetic age.

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Conflict of interest statement

The authors have no conflicts of interest relevant to this article to disclose.

Figures

FIGURE 1
FIGURE 1
Comparison of biological aging measures between survivors (n = 58) and comparators (n = 27). Both age acceleration (AgeAccelGrim and AgeAccelPheno) and pace of aging (DunedinPACE) are higher among survivors versus comparators. Increased epigenetic age compared to chronological age is represented by AgeAccelGrim or AgeAccelPheno values >0 and DunedinPACE >1. p‐Values calculated using t‐tests.
FIGURE 2
FIGURE 2
Biological aging measures by treatment intensity level (ITR‐3). Epigenetic age acceleration (AgeAccelGrim and AgeAccelPheno) and pace of aging (DunedinPACE) are increased among survivors treated with higher intensity therapy. p‐Values calculated using linear regression comparing treatment intensity level combinations.
FIGURE 3
FIGURE 3
Multivariable linear regression models examining associations between biological aging measures and either frailty or myopenia in survivors. Time off treatment denotes change in biological aging measure for every 10 years post‐end of all cancer treatment. BIPOC, black, indigenous and people of color; ITR‐3, intensity of treatment rating, version 3.
See this image and copyright information in PMC

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