Epigenetic Clocks Predict Colorectal Cancer Risk Years Ahead

Researchers have found a strong connection between accelerated biological aging and the development of colorectal cancer in postmenopausal women. The study, published in Aging on July 7, 2025, used blood-based DNA data to estimate biological age and assess how lifestyle and reproductive history might influence cancer risk.

The research team, led by Su Yon Jung at the University of California Los Angeles, analyzed data from the Women's Health Initiative Database for Genotypes and Phenotypes. This dataset includes genetic and health information from white women aged 50 to 79. The researchers focused on a specific molecular measure of aging called epigenetic age, which is based on patterns of DNA methylation, chemical modifications to DNA that affect gene activity without altering the DNA sequence itself.

Molecular clocks used to estimate aging

To estimate biological age, the team used three well-established epigenetic clocks: Horvath's, Hannum's and Levine's. These tools evaluate DNA methylation across the genome to quantify how quickly a person is aging at the cellular level. Blood samples from participants had been collected up to 17 years prior to cancer diagnosis, providing a long-term view of epigenetic changes.

Results showed that women with higher-than-expected epigenetic age were significantly more likely to develop colorectal cancer. In contrast, those whose biological age matched or was lower than their chronological age were less likely to be diagnosed with the disease.

Lifestyle factors influence cancer development

Diet was found to play a modifying role in the relationship between epigenetic aging and cancer. Women with high consumption of fruits and vegetables showed no increased cancer risk, even when they had signs of accelerated aging. Those with both lower fruit and vegetable intake and elevated biological age had a substantially higher risk, with up to a 20-fold increase in likelihood of developing colorectal cancer.

The researchers suggest that a diet rich in plant-based foods may help mitigate cancer risk associated with aging processes at the molecular level.

Hormonal history also linked to aging

The study also examined reproductive health factors. Women who had both ovaries removed before natural menopause had higher epigenetic ages. When combined with signs of accelerated aging, these individuals showed an increased likelihood of developing colorectal cancer. The findings indicate that hormonal and reproductive factors may influence biological aging and associated cancer risk.

Findings validated across independent datasets

To strengthen their conclusions, the authors validated their findings across multiple independent datasets. This supports the potential use of epigenetic aging markers in blood as early indicators of colorectal cancer risk, particularly in aging populations. However, the researchers emphasize the need for replication in large-scale studies before these markers can be used routinely in clinical settings.

Reference: Jung SY, Pellegrini M, Tan X, Yu H. Epigenetic age and accelerated aging phenotypes: a tumor biomarker for predicting colorectal cancer. Aging. 2025. doi: 10.18632/aging.206276

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