Aging and increased cancer risk: exploring the potential of LE8 score to mitigate risk

Given global population aging and the absence of aging-reversal therapies, elucidating the aging-related cancer risk association and developing cancer prevention strategies are imperative. This population-based cohort study analyzed data from the UK Biobank. Aging was assessed through four validated markers, including Klemera-Doubal method (KDM), PhenoAge, leukocyte telomere length (TL) and chronological age. Over a median follow-up of 13.5 years, significant associations between all aging measures and elevated overall cancer risk were observed. False discovery rate (FDR)-corrected analyses revealed a significant association in a biological aging group for seven site-specific cancers, including esophageal, colorectal, pancreatic, skin, kidney, urinary tract cancers, and lymphoma, as evaluated by the four aging markers. A significant interaction (FDR-corrected p < 0.05) between Life's Essential 8 (LE8) and PhenoAge was observed for lung cancer risk. Furthermore, joint analyses revealed that elevated LE8 scores modify this risk for overall cancer among individuals with biological aging, with consistent risk reductions observed for esophageal, gastric, breast, and uterine cancers across all aging markers. These findings suggest that a higher LE8 score is associated with lower cancer risk in the context of biological aging.