Accelerated aging and early-onset colorectal cancer.

Abstract

The rising incidence of early-onset colorectal cancer (EOCRC) challenges existing paradigms of tumorigenesis. Classical models based on cumulative mutational burden, environmental exposure, and hereditary predisposition fail to explain the emergence of malignancy in individuals under 50 years of age. In this review, we propose that EOCRC may be driven by accelerated biological aging and review how core aging processes are prematurely activated in EOCRC. Importantly, these alterations extend beyond the tumor microenvironment and are present in circulating immune cells and inflammatory mediators. We propose that EOCRC develops prematurely in response to environmental, metabolic, genetic, and related factors that systemically accelerate biological aging. This approach reconciles the origin of EOCRC with traditional models of tumorigenesis, while highlighting novel opportunities for early detection, risk stratification, and therapeutic intervention.