Early life sugar rationing and ageing related diseases, biological ageing and mortality.
Early-life nutrition may influence lifelong ageing, yet human evidence is scarce. Using Britain's postwar sugar rationing as a natural experiment, we examine its long-term effects in 64,809 United Kingdom Biobank participants. Exposure to sugar rationing during the first 1,000 days of life is associated with a 9% lower incidence of hallmark-related disease, with a hazard ratio of 0.91 and a 95% confidence interval of 0.88-0.94, and a 19% lower risk of all-cause mortality, with a hazard ratio of 0.81 and a 95% confidence interval of 0.69-0.93. Mediation analysis indicates that the survival association is statistically mediated, by approximately 60%, through differences in incident hallmark-related disease. Rationed individuals show 1.0-1.2-year younger biological ages across multiple clocks and lower organ ages, particularly in the lung, heart, and liver. Proteomic profiling identifies 47 altered proteins, with enrichment of adenosine monophosphate-activated protein kinase and longevity pathways and suppression of mechanistic target of rapamycin signaling. These findings are consistent with international recommendations to limit free or added sugars from the World Health Organization, United States Dietary Guidelines, and American Heart Association, and may inform policy discussions related to sugar taxation and infant food and marketing policies under the United Nations 2030 Agenda.