Epigenetic aging linked to increased colorectal cancer risk in postmenopausal women | Image Credit: © Rasi – stock.adobe.com.
A new study published in Aging (Aging-US) has identified a significant association between accelerated epigenetic aging and increased colorectal cancer (CRC) risk in postmenopausal women, with evidence that lifestyle factors may mitigate this risk.1,2
Researchers led by Su Yon Jung, PhD, MPH, from the University of California, Los Angeles, analyzed data from the Women’s Health Initiative Database for Genotypes and Phenotypes (WHI-dbGaP), which includes genetic and health records of postmenopausal white women aged 50 to 79 years. Blood samples collected up to 17 years prior to CRC diagnosis were examined using 3 DNA methylation–based “epigenetic clocks”: Horvath’s, Hannum’s, and Levine’s. These measures estimate biological age at the molecular level by assessing DNA methylation changes.
“[…]we examined biological aging status in PBLs via three well-established epigenetic clocks—Horvath’s, Hannum’s, and Levine’s […],” the authors reported.
Key findings
The investigators found that women with a higher epigenetic age than their chronological age were significantly more likely to develop CRC. A 1-year increase in DNA methylation age was associated with an approximate 10% increase in CRC risk, with even greater risk when measured in 10-year increments.
Importantly, lifestyle appeared to influence this association. Women with accelerated epigenetic aging who consumed fewer fruits and vegetables had substantially higher CRC risk, with some analyses showing more than a 20-fold increase. Conversely, those with higher fruit and vegetable intake did not demonstrate elevated risk despite accelerated aging markers. This finding suggests that diet may attenuate cancer risk linked to biological aging.
The study also highlighted reproductive factors. Women who underwent bilateral oophorectomy before natural menopause exhibited higher epigenetic age and, when combined with accelerated aging, had a markedly increased risk of CRC. This supports prior evidence that loss of ovarian function before natural menopause may influence carcinogenesis through hormonal pathways.
Validation and implications
To strengthen the findings, the researchers validated their results across several independent datasets, including both blood- and tissue-based cohorts. The consistency of associations supports the potential of blood-based epigenetic markers as predictive tools for CRC risk.
According to the authors, these results underscore the importance of integrating molecular aging measures with traditional risk factors. “Our findings contribute to better understanding of the role of a pre-diagnostic epigenetic aging biomarker and its interplay with lifestyles in CRC carcinogenesis, informing risk stratification strategies for aged individuals,” they concluded.
Clinical relevance
Colorectal cancer remains one of the most common causes of cancer-related death worldwide, with 90% of new cases diagnosed in individuals aged 50 years and older. Chronological age is a well-established risk factor, but it does not capture heterogeneity in biological aging. The use of epigenetic clocks provides a more precise measure of cellular aging and its potential influence on carcinogenesis.
This study suggests that epigenetic aging markers, measurable years before diagnosis, may help identify individuals at higher risk for CRC who could benefit from enhanced surveillance or preventive strategies. Moreover, the findings that dietary patterns may reduce risk highlight a potentially modifiable pathway.
The authors emphasize that while their study offers novel insight, larger independent replication studies are needed. Limitations included a relatively small number of CRC cases and restriction to white postmenopausal women, limiting generalizability to other populations.
Conclusion
The study demonstrates that accelerated epigenetic aging is strongly linked to increased colorectal cancer risk in postmenopausal women, particularly among those with low fruit and vegetable intake or with prior oophorectomy. These findings suggest that blood-based epigenetic biomarkers may provide valuable tools for early risk stratification, while lifestyle interventions such as improved diet could offer protective benefits even among biologically older individuals.
References:
- Impact Journals LLC. Epigenetic aging markers predict colorectal cancer risk in postmenopausal women. Eureklart. August 19, 2025. Accessed August 20, 2025. https://www.eurekalert.org/news-releases/1095138
- Jung SY, Pellegrini M, Tan X, Yu H. Epigenetic age and accelerated aging phenotypes: a tumor biomarker for predicting colorectal cancer. Aging (Albany NY). 2025 Jul 7; 17:1624-1666 . https://doi.org/10.18632/aging.206276