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The effects of aging and maternal protein restriction during lactation on thymic involution and peripheral immunosenescence in adult mice.


Type

Article

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Authors

Heppolette, Chantal AA 
Chen, Jian-Hua 
Carr, Sarah K 
Palmer, Donald B 
Ozanne, Susan E 

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.

Description

Keywords

Gerotarget, developmental programming, immunosenescence, lifespan, maternal diet, thymic involution, Aging, Animal Nutritional Physiological Phenomena, Animals, Blotting, Western, Cells, Cultured, Diet, Protein-Restricted, Female, Flow Cytometry, Fluorescent Antibody Technique, Immunosenescence, Lactation, Mice, Mice, Inbred C57BL, RNA, Messenger, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Thymus Gland

Journal Title

Oncotarget

Conference Name

Journal ISSN

1949-2553
1949-2553

Volume Title

Publisher

Impact Journals, LLC
Sponsorship
British Heart Foundation (None)
Medical Research Council (MC_UU_12012/4)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_PC_12012)
This work was supported by the BBSRC and the MRC. SEO is funded by the University of Cambridge MRC Metabolic Diseases Unit (MRC_MC_UU_12012/4).