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The Effect of Maternal Protein Restriction During Lactation on Thymic Involution and Peripheral Immunosenescence in Adult Mice

Presented at the Neonatal Society 2014 Autumn Meeting.

Heppolette CAA1, Chen J-H1, Carr SK1, Palmer DB2, Ozanne SE1

1 University of Cambridge, Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust- MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, CB20QQ, UK
2 Immune Regulation and Cancer Research Group, Department of Comparative Biomedical Sciences, RVC, London NW10TU, UK

Background: Environmental factors such as nutrition during early life can influence long-term health, a concept termed developmental programming. Initial studies showed effects on metabolic health but recent studies have also demonstrated effects on ageing, longevity and immunity (1). Given that dysfunction of the immune system is responsible for increased infection, cancer and autoimmune diseases in the elderly, we hypothesise that the adaptive immune system can also be affected by early nutrition, and which may mediate the effect on lifespan.

Methods: C57BL/6 mice were mated and dams were fed an ad libitum diet to establish two groups: Controls (offspring born to and suckled by dams fed a control diet) and the post-natal low protein (PLP) group (offspring of control dams cross-fostered and suckled by dams fed the low protein diet). At 21d, 3m, 18m and 23m fresh thymic and splenic tissues were removed for flow cytometry analysis, confocal microscopy and RNA analysis. All procedures on animals were conducted under the British Animals (Scientific Procedures) Act (1986).

Results: Maternal protein restriction during lactation in mice, that is known to prolong lifespan, slowed ageing of both the central and peripheral immune systems. PLP offspring had a significant increase in thymic cellularity and number of T cells across their lifespan compared to control animals. These animals also demonstrated a less marked age-associated decrease in CD3 expression on thymocytes in old age. Therefore PLP animals demonstrated reducing thymic ageing compared to controls. 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 ageing. A slower rate of splenic ageing in PLP animals would be expected to result in decreased susceptibility to infection and neoplasia.

Conclusion: In conclusion nutritionally-induced slow postnatal growth leads to delayed ageing of the adaptive immune system, which may contribute towards the extended lifespan that is observed in these animals.

Corresponding author: chantal.heppolette07@imperial.ac.uk

This work was supported by the BBSRC and MRC

1. Chen, J.H., Tarry-Adkins, J.L., Heppolette, C.A., Palmer, D.B., and Ozanne, S.E. (2009). Early-life nutrition influences thymic growth in male mice that may be related to the regulation of longevity. Clin Sci (Lond) 118, 429-438.

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