Trajectories of physical function and biological aging in generally healthy older adults with and without incident invasive cancer over a three-year follow-up: findings from the DO-HEALTH study

Cancer is associated with biological aging and functional decline; however, few studies have simultaneously examined objective changes in physical function and biological aging in older adults who develop cancer. We therefore compared functional and accelerated aging in generally healthy adults with and without incident invasive cancer, using data from DO-HEALTH, a three-year, randomized controlled trial including 2152 participants (mean age: 74.9 years, 61.1% women), free of major health conditions. Functional aging was assessed by the Short Physical Performance Battery, handgrip strength, gait speed, and five-times sit-to-stand test (STS). Biological aging was measured in a subsample (n = 777) using Horvath, Hannum, GrimAge and PhenoAge clocks, and DunedinPACE. Participants with incident cancer showed a greater decline in STS (Δ adjusted means [AM]: 0.64 s [95% CI 0.06, 1.22]) and grip strength (ΔAM -1.77 kPa [-3.51, -0.03]). Furthermore, baseline biological aging was accelerated between 3.52 and 6.77 months, measured by Horvath, Hannum, and PhenoAge clocks. Findings support the geroscience hypothesis linking greater phenotypic functional decline to accelerated biological aging in older adults with incident cancer. The data for this observational analysis stem from the DO-HEALTH clinical trial, which was prospectively registered (clinicaltrials.gov; NCT01745263; registered on December 10, 2012).