Maternal protein restriction leads to early life alterations in the expression of key molecules involved in the aging process in rat offspring.
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-beta, 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.
Martin-Gronert
Malgorzata S
MS
Department of Clinical Biochemistry, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. msm32@cam.ac.uk
Tarry-Adkins
Jane L
JL
Cripps
Roselle L
RL
Chen
Jian-Hua
JH
Ozanne
Susan E
SE
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000833:Animals, Suckling; D001835:Body Weight; D018753:Diet, Protein-Restricted; D004044:Dietary Proteins / Q000494:pharmacology*; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008098:Litter Size; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
D004044:Dietary Proteins; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; C494920:Akt1 protein, rat; C494923:Akt2 protein, rat; D051057:Proto-Oncogene Proteins c-akt; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D037761:Sirtuins; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat