Nutrition and growth rate during early life can influence later health and lifespan. We have demonstrated previously that low birthweight, resulting from maternal protein restriction during pregnancy followed by catch-up growth in rodents, was associated with shortened lifespan, whereas protein restriction and slow growth during lactation increased lifespan. The underlying mechanisms by which these differences arise are unknown. In the present study, we report that maternal protein restriction in mice influences thymic growth in early adult life. Offspring of dams fed a low-protein diet during lactation (PLP offspring) had significant thymic growth from 21 days to 12 weeks of age, whereas this was not observed in control mice or offspring of dams fed a low-protein diet during pregnancy (recuperated offspring). PCNA (proliferating-cell nuclear antigen) and SIRT1 (silent information regulator 1) protein levels at 21 days of age were significantly higher in the thymus from both PLP mice (P<0.001 and P<0.05 respectively) and recuperated mice (P<0.001 and P<0.01 respectively) compared with controls. At 12 weeks, PLP mice maintained a higher SIRT1 level, whereas PCNA was decreased in the thymus from recuperated offspring. This suggests that mitotic activity was initially enhanced in the thymus from both PLP and recuperated offspring, but remained sustained into adulthood only in PLP mice. The differential mitotic activity in the thymus from PLP and recuperated mice appeared to be influenced by changes in sex hormone concentrations and the expression of p53, p16, the androgen receptor, IL-7 (interleukin-7) and the IL-7 receptor. In conclusion, differential thymic growth may contribute to the regulation of longevity by maternal diet.

Environmental factors such as nutrition during early life can influence long-term health, a concept termed developmental programming. Initial research was focused towards the effects on metabolic health but more recent studies have demonstrated effects on parameters such as lifespan and immunity. In this study we report that maternal protein restriction during lactation in mice, that is known to prolong lifespan, slows aging of the central and peripheral immune systems. Offspring of dams fed a postnatal low-protein (PLP) diet during lactation had a significant increase in thymic cellularity and T cell numbers across their lifespan compared to controls, and a less marked age-associated decrease in thymocyte cluster of differentiation (CD) 3 expression. PLP animals also demonstrated increased relative splenic cellularity, increased naïve: memory CD4+ and CD8+ T cell ratios, increased staining and density of germinal centres, and decreased gene expression of p16 in the spleen, a robust biomarker of aging. A slower rate of splenic aging in PLP animals would be expected to result in decreased susceptibility to infection and neoplasia. In conclusion nutritionally-induced slow postnatal growth leads to delayed aging of the adaptive immune system, which may contribute towards the extended lifespan observed in these animals.

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