Early-life nutrition influences thymic growth in male mice that may be related to the regulation of longevity.

Jian-Hua Chen,Susan E Ozanne,Donald B Palmer,Chantal A A Heppolette,Jane L Tarry-Adkins

doi:10.1042/cs20090429

Jian-Hua Chen, Susan E Ozanne + Show 3 more

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https://doi.org/10.1042/cs20090429

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Abstract

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.

Highlights

Abstract an Nutrition and growth rate during early life can influence later health and lifespan
The above findings suggest that maternal nutrition can alter thymic size and cellular division, given that these animals have varying lifespan, these observations imply that the early life events that affect longevity, which we have identified using this animal model, may influences the aging of the thymus
To gain further insight into the possible mechanisms that are likely to impact on the aging of the thymus, we examined the levels of mRNA expression of various genes that are associated with thymic growth and function [13,23,24,25] in 21 day old thymus from all three animal groups

Summary

Introduction

Abstract an Nutrition and growth rate during early life can influence later health and lifespan. Subsequent studies further established that poor fetal growth is associated with later risk of adult diseases including cardiovascular disease, metabolic syndrome and type 2 diabetes [2] This led to the concept of the fetal/early origins of adult disease which is widely known as developmental origins of health and disease [3]. The developmental origins hypothesis proposes that during critical periods of fetal and postnatal mammalian development, nutrition and other environmental factors induce adaptive responses These lead to permanent changes in metabolism, hormone production and tissue sensitivity to hormones that may affect development of various organs, resulting in long-term alteration of physiology and metabolism and adult disease susceptibility [4]

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