Biological Aging Linked to Colorectal Cancer Risk Regardless of Gender

Measuring biological age (BA) could offer new insights into colorectal cancer (CRC) risk, according to a study finding that accelerated biological aging was significantly associated with a higher prevalence of CRC, with the strongest link observed in adults over 65 years.¹

Biological age, rather than chronological age, may be a stronger predictor of colorectal cancer risk—especially in older adults. | Image credit: smolaw11 - stock.adobe.com

The cross-sectional study is published in Frontiers in Medicine.

“To date, the association between BA measures and CRC has not been investigated,” wrote the researchers of the study. “To address this gap, this study aims to assess the relationship between KDMAge [Klemera-Doubal method age] and PhenoAge [phenotypic age] and the prevalence of CRC, and to further validate this relationship across different population subgroups.”

Chronological age counts the years a person has lived, while biological age reflects how well their body is functioning based on various health markers.² Unlike chronological age, which is the same for everyone born in a given year, biological age can differ widely due to genetics, lifestyle, and environmental factors, making it a more personalized measure of aging.

In this study, the researchers analyzed data from the National Health and Nutrition Examination Survey to investigate the relationship between BA and CRC.¹ Biological age was measured using 2 established methods: Klemera-Doubal method age (KDMAge) and phenotypic age (PhenoAge), both derived from 13 common clinical biomarkers. The study compared CRC prevalence across quartiles of these BA indicators. Additionally, the researchers assessed the strength of the association between BA and CRC, accounting for potential confounding factors.

The study analyzed data from 36,684 participants and found a significant association between biological age and CRC prevalence. CRC prevalence increased consistently across ascending quartiles of chronological age, KDMAge, and PhenoAge, even when accounting for gender and age subgroups (all P for trend < .05). Notably, individuals in higher quartiles of PhenoAge acceleration had a greater weighted prevalence of CRC compared with those in lower quartiles (P for trend < .05). Accelerated PhenoAge was significantly linked to higher CRC prevalence (OR, 1.767; 95% CI, 1.236-2.524; P = .002), with this association being particularly strong in individuals over 65 years old (OR, 1.655; 95% CI, 1.143-2.397, P = .008).

While this study is the first to examine the relationship between biological age and CRC in a US adult population, the researchers noted it had several limitations. Its cross-sectional design prevented causality, leaving open the possibility of reverse causation. Additionally, reliance on self-reported data introduced potential biases, particularly regarding CRC history and lifestyle factors. Unmeasured confounders, such as genetic predisposition and environmental exposures, may also have influenced the observed associations. Furthermore, the study was unable to account for years since CRC diagnosis and did not explore racial differences in the BA-CRC relationship, highlighting the need for future research.

Despite these limitations, the researchers believe the study highlights an important association between biological aging and CRC risk.

“This also provides a clinically utilizable biological means to identify high-risk individuals among the elderly. Therefore, independent of the increase in chronological age, the intensified degree of biological aging behind accelerated BA becomes a covert factor for CRC risk,” wrote the researchers. “This offers new evidence for the unexplained residual risk increase in CRC associated with population aging, and is crucial for the precise identification of early-risk groups for CRC, particularly in the prevention of CRC, especially targeted toward the elderly.”

References

1. Wang S, Wang K, Wang X. Association between accelerated biological aging and colorectal cancer: A cross-sectional study. Frontiers in Medicine. 2025;12. doi:10.3389/fmed.2025.1533507

2. Understanding the difference between biological age and chronological age. Mayo Clinic. July 30, 2024. Accessed March 11, 2025. https://mcpress.mayoclinic.org/healthy-aging/understanding-the-difference-between-biological-age-and-chronological-age/