Abstract
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.
Highlights
The developmental origins of health and disease hypothesis describes the phenomenon whereby exposures in utero and early postnatal life modulate long-term health [1]
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
Given that our previous study demonstrated an effect of maternal diet on thymic weight, we further investigated the effect of maternal diet on thymic cellularity [13]
Summary
The developmental origins of health and disease hypothesis describes the phenomenon whereby exposures in utero and early postnatal life modulate long-term health [1]. Original studies focused on how early life events increase the susceptibility to metabolic diseases such as type 2 diabetes and cardiovascular disease [2,3,4]. Interventions can be beneficial, evidenced by numerous studies showing that the intake of breast milk significantly reduces the risk of developing metabolic syndrome in later life [8]. The development of the adaptive immune system in mammals occurs during fetal and early postnatal growth periods, during which they are vulnerable to environmental insults [9]. Another study in humans observed that a longer period of breastfeeding increased thymic volume in infants, which is indicative of increased immune capacity [11]. Previous work in our laboratory revealed that offspring born to normally fed dams and suckled by protein restricted dams (postnatal low protein: PLP offspring), demonstrated slow growth during lactation, extended longevity and continued www.impactjournals.com/oncotarget
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