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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/R494    most recent 00530.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Martin-Gronert, M. S. Articles by Ozanne, S. E. PubMed PubMed Citation Articles by Martin-Gronert, M. S. Articles by Ozanne, S. E.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Maternal protein restriction leads to early life alterations in the expression of key molecules involved in the aging process in rat offspring

Department of Clinical Biochemistry Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom

Submitted 24 July 2007 ; accepted in final form 5 December 2007

Recent findings demonstrate that nutrition during the fetal and neonatal periods can affect the life span of an organism. Our previous studies in rodents using a maternal low protein diet have shown that limiting protein and growth during lactation [postnatal low protein (PLP group)] increases longevity, while in utero growth restriction (IUGR) followed by "catch up growth" (recuperated group) shortens life span. The aim of this study was to investigate mechanisms in early postnatal life that could underlie these substantial differences in longevity. At weaning, PLP animals had improved insulin sensitivity as suggested by lower concentrations of insulin required to maintain concentrations of glucose similar to those of the control group and significant upregulation of insulin receptor-β, IGF-1 receptor, Akt1, Akt2, and Akt phosphorylated at Ser 473 in the kidney. These animals also had significantly increased SIRT1 (mammalian sirtuin) expression. Expression of the antioxidant enzymes catalase, CuZnSOD, and glutathione peroxidase-1 was elevated in these animals. In contrast, recuperated animals had a significantly increased fasting glucose concentration, while insulin levels remained comparable to those of the control group suggesting relative insulin resistance. MnSOD expression was increased in these animals. These data suggest that early nutrition can lead to alterations in insulin sensitivity and antioxidant capacity very early in life, which may influence life span.

insulin signaling; antioxidant enzymes; longevity; SIRT1