Delayed nutrient delivery relative to an individual regenerative phase is linked to reduced progenitor responsiveness and shaped by inherited factors

Background Although temporal control of morphogenesis by intrinsic oscillators is well established, the impact of nutrient‐delivery timing on tissue renewal remains underexplored. This study aimed (i) to determine whether the phase of nutrient intake with respect to each organism’s endogenous regenerative clock predicts indices of somatic restoration and (ii) to quantify the relative genetic and environmental contribution to nutrient‐timing traits. Methods In 92 adult isogenic sibling pairs, regenerative capacity was evaluated with a standardized appendage resection–blastema growth assay. Components of nutrient timing (delivery phase, intraday nutrient distribution, and feeding frequency) were extracted from five-day intake logs. The nutrient midpoint was defined as the clock time at which 50 % of daily macronutrients were provided. Circadian positioning of feeding was computed as the interval between feeding times and the corrected midpoint of the organism’s mitotic peak, a validated chronobiological marker of regenerative phase. Heritability of nutrient-timing traits was assessed by comparing intrapair correlations between monozygotic and dizygotic siblings and by fitting structural equation models. Findings Among nutrient-timing variables, the circadian phase of the nutrient midpoint (CPNM) exhibited the strongest associations. A later CPNM correlated with diminished blastema expansion, reflected by a lower Proliferative Index (β = 0.304, p = 5.9 × 10⁻⁴) and elevated Scar Density Score (β = −0.258, p = 0.011), as well as higher residual collagen deposition (β = −0.259, p = 0.013), after adjustment for sex, age, total energy intake, and rest duration. Later CPNM also showed consistent associations with increased trunk adipocyte area and dermal thickness. All nutrient-timing metrics displayed moderate to high heritability and were tightly coupled to individual mitotic timing. Interpretation Nutrient provision that lags an organism’s intrinsic regenerative phase is associated with attenuated progenitor activation. Advancing the bulk of nutrient intake to earlier phases of the regenerative clock may enhance tissue repair; however, inherited factors could influence both feasibility and efficacy of such chrononutritional interventions. Larger cohorts are warranted to validate these findings.