Early-life nutritional deprivation and multimorbidity in middle- aged and older adults: a longitudinal exploratory mediation analysis of biological aging.

OBJECTIVE: This study aimed to examine the longitudinal association between childhood food deprivation and physical-psychological-cognitive multimorbidity (PPC-MM), and to explore whether Light-BioAge mediates this association. METHODS: This study included 4546 participants aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS). Childhood food deprivation was retrospectively assessed as none, moderate, or extreme. Incident PPC-MM was identified during 2011-2020 follow-up. Cox regression examined the longitudinal association, and causal mediation analysis explored the potential mediating effect of Light-BioAge. RESULTS: In the unadjusted model, compared with no deprivation, moderate deprivation was associated with a 20% increased risk of PPC-MM (HR = 1.20, 95% CI: 1.10-1.31), and extreme deprivation with a 60% increased risk (HR = 1.60, 95% CI: 1.40-1.82). After adjusting for socio-demographic factors, the HRs were 1.19 (95% CI: 1.08-1.30) and 1.44 (95% CI: 1.26-1.65), respectively. Further adjustment for lifestyle and health-related covariates yielded HRs of 1.17 (95% CI: 1.07-1.28) and 1.43 (95% CI: 1.25-1.63). Kaplan-Meier survival curves showed significant differences in cumulative incidence among the three groups (Log-rank test, P < 0.001). Subgroup analyses revealed consistent directionality across sex, age, education, residence, and BMI strata, with no significant interactions (all P for interaction > 0.05). Exploratory causal mediation analysis indicated that Light-BioAge accounted for a small proportion (4.9% and 5.3%) of the total effects, with indirect effects close to the null (HR = 1.01, 95% CI: 1.00-1.01). CONCLUSION: Childhood food deprivation is robustly associated with PPC-MM in a dose-response manner. The exploratory effect of Light-BioAge suggests that other pathways may play more important roles. These findings support integrating early-life nutritional risk assessment into healthy aging strategies.