Exploring the Complex Relationship between Biological Aging and Cancer in a Prospective Italian Population Cohort

Cancer is often associated with age-related chronic conditions; however, the role of biological aging as a potential risk factor for cancer remains unclear and largely unexplored. To clarify this link, we tested the influence of two biological aging measures in an Italian prospective population cohort, the Moli-sani study (N=24,325; age ≥35 years; 51.9% women). For each participant these were based on the difference between first and a second-generation blood-based biological age estimates (BloodAge and PhenoAge) and chronological age. The resulting biological aging acceleration measures (BloodAgeAcc and PhenoAgeAcc) were tested for association with cancer mortality, first hospitalization and incident fatal/non-fatal cases, using multivariable Cox proportional hazard models. We analyzed 22,985 apparently cancer-free participants with mortality data available (median follow-up 13.1 years) and found independent increases in mortality rates per one-year increase in PhenoAgeAcc and BloodAgeAcc. Additionally, statistically significant increased risk of cancer hospitalizations was observed for PhenoAgeAcc. The analysis of incident cancers for different body sites identified both increased and decreased risks associated with biological aging acceleration. BloodAgeAcc was indeed weakly associated with a reduced risk of both breast and prostate cancer, but with an increased risk of pancreatic cancer, while PhenoAgeAcc was associated with an increased risk of lung and renal cancer. Our findings suggest that biological aging acceleration may differently impact cancer-related risks, with protective effects for some cancers versus increased risks for others. Further independent cohort studies are needed to clarify the translational clinical impact of these findings.