Birthweight and Breastfeeding Shape Patterns of Biological Aging Across Adult Organs.

Early-life nutrition may influence long-term health, but its impact on organ-specific biological aging is unclear. We investigated associations of birthweight and breastfeeding with multi-organ aging and potential mediating pathways in adulthood. Using UK Biobank data, we examined associations of retrospectively reported birthweight (n = 21,446) and breastfeeding history (n = 29,713) with 19 proteomics-derived aging indices, comprising 18 organ-specific indices and one composite index. Multivariable linear regression assessed individual and joint associations, effect modification by sex and socioeconomic factors, and mediation by allostatic load (AL) and C-reactive protein (CRP). Higher birthweight was inversely associated with aging across 11 organ systems (all FDR-adjusted p < 0.05), with strongest associations in the intestine (β = -0.069), esophagus (β = -0.055), and stomach (β = -0.053). Breastfeeding exposure was associated with slower aging of the intestine (β = -0.047) and adrenal gland (β = -0.030), but modestly faster thyroid aging (β = 0.033). The combination of higher birthweight and breastfeeding was associated with favorable aging profiles, particularly in the intestine (β = -0.13), stomach (β = -0.09), and kidney (β = -0.08). Associations were stronger among females and socioeconomically advantaged or healthier-behavior subgroups. AL mediated up to 35.3% of the birthweight-aging association, whereas CRP showed minimal mediation. Higher birthweight and breastfeeding, particularly in combination, produce the most favorable profiles of multi-organ biological aging in adulthood, with AL partially mediating these effects. These findings provide novel evidence that prenatal and postnatal nutrition leave enduring, system-wide imprints on adult aging trajectories.