Maternal Protein Restriction Affects Postnatal Growth and the Expression of Key Proteins Involved in Lifespan Regulation in Mice
Open Access
- 24 March 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (3), e4950
- https://doi.org/10.1371/journal.pone.0004950
Abstract
We previously reported that maternal protein restriction in rodents influenced the rate of growth in early life and ultimately affected longevity. Low birth weight caused by maternal protein restriction followed by catch-up growth (recuperated animals) was associated with shortened lifespan whereas protein restriction and slow growth during lactation (postnatal low protein: PLP animals) increased lifespan. We aim to explore the mechanistic basis by which these differences arise. Here we investigated effects of maternal diet on organ growth, metabolic parameters and the expression of insulin/IGF1 signalling proteins and Sirt1 in muscle of male mice at weaning. PLP mice which experienced protein restriction during lactation had lower fasting glucose (P = 0.038) and insulin levels (P = 0.046) suggesting improved insulin sensitivity. PLP mice had higher relative weights (adjusted by body weight) of brain (P = 0.0002) and thymus (P = 0.031) compared to controls suggesting that enhanced functional capacity of these two tissues is beneficial to longevity. They also had increased expression of insulin receptor substrate 1 (P = 0.021) and protein kinase C zeta (P = 0.046). Recuperated animals expressed decreased levels of many insulin signalling proteins including PI3 kinase subunits p85α (P = 0.018), p110β (P = 0.048) and protein kinase C zeta (P = 0.006) which may predispose these animals to insulin resistance. Sirt1 protein expression was reduced in recuperated offspring. These observations suggest that maternal protein restriction can affect major metabolic pathways implicated in regulation of lifespan at a young age which may explain the impact of maternal diet on longevity.This publication has 57 references indexed in Scilit:
- Tissue-specific regulation of SIRT1 by calorie restrictionGenes & Development, 2008
- SIRT1 transgenic mice show phenotypes resembling calorie restrictionAging Cell, 2007
- Sirtuins: critical regulators at the crossroads between cancer and agingOncogene, 2007
- Sirtuins in mammals: insights into their biological functionBiochemical Journal, 2007
- Critical nodes in signalling pathways: insights into insulin actionNature Reviews Molecular Cell Biology, 2006
- Overview of caloric restriction and ageingMechanisms of Ageing and Development, 2005
- The Plasticity of Aging: Insights from Long-Lived MutantsCell, 2005
- daf-2 , an Insulin Receptor-Like Gene That Regulates Longevity and Diapause in Caenorhabditis elegansScience, 1997
- A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegansNature, 1996
- A C. elegans mutant that lives twice as long as wild typeNature, 1993