Combined association between phenotypic age acceleration and dietary fiber intake with mortality in middle-aged and elderly cancer survivors.

objectiveThis study examined the associations of phenotypic age (PhenoAge) acceleration and dietary fiber intake with mortality risk among middle-aged and older adult cancer survivors.

methodsThis study analyzed data from 2958 cancer survivors aged 40 and older using National Health and Nutrition Examination Survey (NHANES) 2003-2018. Dietary fiber intake was assessed via two 24-hour dietary recalls, calculated using the USDA database. High dietary fiber intake was defined as the top quartile. Biological age was estimated using the PhenoAge algorithm with 8 biomarkers, defining accelerated aging as PhenoAge >0. Mortality status was determined through linkage with the National Death Index. Cox regression models and Kaplan-Meier curves were used to examine the separate and combined association of dietary fiber intake and PhenoAge acceleration on mortality, adjusting for multiple covariates. Multiplicative interaction was assessed by including a product term in the cox regression models, while additive interaction was examined using the relative excess risk due to interaction (RERI) and the attributable proportion (AP). Restricted cubic spline models were applied to estimate the linear/non-linear relationships between PhenoAge acceleration, dietary fiber intake, and mortality risk. Sensitivity analysis was used to validate previous findings.

resultsThe study included 2,958 cancer survivors with a baseline mean age of 65.58 years. During a 17-year follow-up (median [IQR]: 79 [42-125] months), 915 participants died. Accelerated aging had elevated risk of all-cause (HR (95% CI), 2.12 (1.78, 2.52), P<0.001), cardiovascular (HR (95% CI), 1.72 (1.18, 2.51), P=0.005), cancer (HR (95% CI), 2.68 (2.00, 3.58), P<0.001), and non-cancer/non-cardiovascular mortality (HR (95% CI), 2.04 (1.58, 2.63), P<0.001). Low dietary fiber intake was linked to increased all-cause (HR (95% CI), 1.31 (1.05, 1.63), P=0.015), cancer (HR (95% CI), 1.59 (1.11, 2.27), P=0.011), and non-cancer/non-cardiovascular mortality (HR (95% CI), 1.64 (1.11, 2.43), P=0.013). The "Accelerated aging & low dietary fiber" group had the highest all-cause mortality risk (HR (95% CI), 2.45 (1.81, 3.33), P<0.001), cancer mortality risk (HR (95% CI), 3.40 (2.16, 5.37), P<0.001), non-cancer/non-cardiovascular mortality risk (HR (95% CI), 3.18 (1.91, 5.29), P<0.001), compared to the "Non-accelerated aging & high dietary fiber" group. Furthermore, a significant additive interaction was observed between PhenoAge acceleration and low dietary fiber intake on cancer mortality (RERI = 1.44, 95% CI: 0.23-2.64; AP = 0.42, 95% CI: 0.08-0.76). The results of the sensitivity analysis excluding samples that died within two years are consistent with the main analysis.

conclusionsPhenoAge acceleration and lower dietary fiber intake are associated with increased mortality risk in middle-aged and elderly cancer survivors. Notably, dietary fiber intake significantly modified the association between PhenoAge acceleration and cancer mortality.