Oncotarget

Research Papers: Gerotarget (Focus on Aging):

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

Chantal A. A. Heppolette _, Jian-Hua Chen, Sarah K. Carr, Donald B. Palmer and Susan E. Ozanne

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Oncotarget. 2016; 7:6398-6409. https://doi.org/10.18632/oncotarget.7176

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Abstract

Chantal A. A. Heppolette1, Jian-Hua Chen1, Sarah K. Carr1, Donald B. Palmer2 and Susan E. Ozanne1

1 University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK

2 Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London, UK

Correspondence to:

Chantal A. A. Heppolette, email:

Keywords: developmental programming, immunosenescence, lifespan, maternal diet, thymic involution, Gerotarget

Received: September 21, 2015 Accepted: January 25, 2016 Published: February 03, 2016

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.


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