title: Early-life nutrition influences thymic growth in male mice that may be related to the regulation of longevity.
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.
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, U.K. jhc36@cam.ac.uk
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Chen
authors.forename: Jane L
authors.initials: JL
authors.lastname: Tarry-Adkins
authors.forename: Chantal A A
authors.initials: CA
authors.lastname: Heppolette
authors.forename: Donald B
authors.initials: DB
authors.lastname: Palmer
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
mesh_terms: D000824:Animal Nutritional Physiological Phenomena / Q000502:physiology*; D000818:Animals; D002453:Cell Cycle; D016207:Cytokines / Q000235:genetics; D018753:Diet, Protein-Restricted; D004958:Estradiol / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D008136:Longevity / Q000502:physiology*; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D011247:Pregnancy; D013739:Testosterone / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000254:growth & development*
chemical_list: D016207:Cytokines; D013739:Testosterone; D004958:Estradiol