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Poor maternal nutrition followed by accelerated postnatal growth leads to telomere shortening and increased markers of cell senescence in rat islets

University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK

¹ Correspondence: University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Level 4, Box 289, Addenbrooke’s Treatment Centre, Addenbrooke’s Hospital, Hills Rd. Cambridge, CB2 OQQ, UK. E-mail: janeadkins{at}googlemail.com

Low birth weight (LBW) followed by accelerated postnatal growth is associated with increased risk of developing age-associated diseases such as type 2 diabetes. Gestational protein restriction in rats causes LBW, β-cell dysfunction, and reduced longevity. These effects may be mediated by accelerated cellular aging. This study tested the hypothesis that LBW followed by rapid postnatal catch-up growth leads to islet telomere shortening through alterations in antioxidant defense capacity, stress/senescence marker proteins, and DNA repair mechanisms at the gene expression level. We used our rat model of gestational protein restriction (recuperated offspring) and control offspring. Southern blotting revealed shorter (P<0.001) islet telomeres in recuperated animals compared to controls. This was associated with increased expression of peroxiredoxin 1 (P<0.05), peroxiredoxin 3 (P<0.01), and heme oxygenase-1 (HO-1) (P<0.05), which are up-regulated under stress conditions. MnSOD expression was significantly (P<0.05) decreased in recuperated offspring, suggesting partial impairment of mitochondrial antioxidant defenses. Markers of cellular senescence p21 and p16 were also increased (P<0.01 and P<0.05, respectively) in the recuperated group. We conclude that maternal diet influences expression of markers of cellular stress and telomere length in pancreatic islets. This may provide a mechanistic link between early nutrition and growth and type 2 diabetes.—Tarry-Adkins, J. L., Chen, J. H., Smith, N. S., Jones, R. H., Cherif, H., Ozanne, S. E. Poor maternal nutrition followed by accelerated postnatal growth leads to telomere shortening and increased markers of cell senescence in rat islets.

Key Words: cellular stress • antioxidative defense • DNA damage • DNA repair

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