Biological Aging in Combination with Lifestyle Factors in the Blood-Based Methylome - A Biomarker for Colorectal Cancer Susceptibility in African American Women

Sep 23, 2026

DNA methylation (DNAm)-based age estimators are highly accurate across tissues, yet their mechanistic relevance to colorectal cancer (CRC) remains insufficiently defined. CRC burden is higher in aged African Americans than in whites, motivating AA-specific epigenetic aging studies. Using prediagnostic peripheral blood leukocyte DNAm from 621 postmenopausal AA women, the study links epigenetically older age and age acceleration with altered CRC risk, modulated by lifestyle factors including estrogen use and healthy diet.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

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Abstract

Introduction

Volume 17, Number 2; 1052-1067, April 2026 [http://dx.doi.org/10.14336/AD.2025.0099](http://dx.doi.org/10.14336/AD.2025.0099) Original Article Biological Aging in Combination with Lifestyle Factors in the Blood-Based Methylome: A Biomarker for Colorectal Cancer Susceptibility in African American Women Su Yon Jung1,2,3*, Matteo Pellegrini4, Herbert Yu5 1Translational Sciences Section, School of Nursing, University of California, Los Angeles, Los Angeles, CA 90095, USA; 2Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; 3Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; 4Department of Molecular, Cell and Developmental Biology, Life Sciences Division, University of California, Los Angeles, Los Angeles, CA 90095, USA; 5Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA. [Received January 22, 2025; Revised March 10, 2025; Accepted March 12, 2025] ABSTRACT: DNA methylation (DNAm)–based estimators of age are highly accurate for biological aging in multiple tissues, but their functional roles remain poorly understood in colorectal cancer (CRC), an age-related disease whose burden is higher in aged African Americans (AAs) than in whites. A greater rate of epigenetic age deviation from chronologic age was observed in AAs’ colorectal tissues than in whites’, emphasizing AA-specific investigation for epigenetic aging in CRC. Tumor tissue–based DNAm exclusively reflects cancerization, raising a question about its cancer predictability. A prediagnostic peripheral blood leukocyte (PBL)–based DNAm aging marker may thus provide keys to CRC etiology and prevention. From the largest study cohort, we examined 621 AA postmenopausal women 50–79 years old, including a subset of 14 who developed CRC, with their prediagnostic PBL-DNAm. Using three well-known pan-tissue– and blood–based epigenetic clocks, we evaluated correlations with CRC risk and to what degree the cancer risk is modified by lifestyle factors. Epigenetically older age and increased age acceleration were associated with reduced risk for CRC development. Of note, when women had accelerated aging phenotypes at screening, a substantial increased CRC risk was observed in shortterm users of exogeneous estrogen, while a profound risk reduction was shown in women eating a healthy diet. Our study contributes to better understanding of the exertion of lifestyle factors in combination with methylomebased aging in colorectal carcinogenesis, detecting a prediagnostic PBL-based aging biomarker that promotes epigenetically targeted strategies tailored to aged AA women at high risk. Key words: DNA methylation–based marker for age, epigenetic aging, pre-diagnostic DNA methylation, colorectal cancer, tumorigenesis, exogenous estrogen, diet, African American, postmenopausal women INTRODUCTION Colorectal cancer (CRC) is a leading cause of cancer incidence and mortality in the U.S.A. and globally [1-3] . CRC is age dependent, with 90% of new cases developing after age 50 [4, 5], highlighting that age is an important risk factor. In particular, African Americans (AAs) experience a greater CRC burden than whites, having an approximately 30% higher incidence rate in those overage 50 than their white counterparts have [6, 7] . Aging is not just referred to as an increase in chronologic age but is also viewed as “biological aging,”which reflects a gradual decline in biological function [8] . Exposures to harmful environments and behavioral | factors may affect a variety of biological aging processes | heterogeneity of age, sex, and race combination in the | | --- | --- | | at molecular levels, leading to cellular vulnerability, cell | sample; and population-specific environmental and | | senescence, genomic and epigenomic instability, | behavioral profiles. | | mitochondrial dysfunction, and telomere attrition [9]

FAQs

Why do the researchers focus on African American women in colorectal cancer risk?

CRC burden is higher in African Americans than in whites, particularly after age 50. The study highlights the need for AA-specific investigation of epigenetic aging in CRC.

What data source is used to build the prediagnostic epigenetic aging marker?

The study uses prediagnostic peripheral blood leukocyte (PBL)–based DNAm, which is obtained from women before CRC development.

How do lifestyle factors influence the relationship between accelerated aging and CRC risk?

When women showed accelerated aging at screening, CRC risk increased for short-term users of exogenous estrogen, while women following a healthy diet showed a substantial risk reduction.

Sep 23, 2026

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