Ultra-processed foods, biological ageing, and all-cause mortality risk: a prospective cohort study using 172,225 participants from UK Biobank.

Ultra-processed foods (UPF) are increasingly linked to negative health outcomes, including chronic diseases and mortality. Recent evidence suggests that UPF may accelerate biological ageing, potentially explaining their harmful effects. Therefore, this study was aimed to investigate associations between UPF intake categories and mortality risk, examining biological ageing's mediating and modifying effects. We used a prospective cohort design including 172,225 participants in the UK Biobank who completed 24-h dietary recall questionnaires. UPF were classified according to the NOVA system. Cox proportional hazards models were used to evaluated associations between UPF intake and both all-cause and cause-specific mortality. Biological ageing was assessed using PhenoAge acceleration, with the bootstrap method examined mediation effects and delta method assessed interaction between UPF intake and biological ageing on mortality risk. Participants consuming > 8 servings/day of total UPF showed higher mortality risk compared to those consuming ≤ 3.5 servings/day (HR = 1.15; 95% CI 1.07-1.23). Analyses by UPF subgroups revealed positive associations with mortality risk for plant-based UPF (HR = 1.02, 95% CI 1.01-1.03), artificial sweeteners (HR = 1.05, 95% CI 1.03-1.08), and beverages (HR = 1.04, 95% CI 1.03-1.05). Biological ageing mediated 14.4%, 27.5%, and 8.3% of these associations, respectively. A significant additive interaction was observed between high packaged food intake (> 1 servings/day) and accelerated biological ageing on mortality risk (RERI = 0.21, 95% CI 0.01-0.41), while breakfast cereals showed potential protective interactions. UPF consumption may increase mortality risk through biological ageing, with varying effects across subgroups. Strategic dietary modifications, reducing harmful UPF while potentially increasing protective ones, may help mitigate mortality risks.