Low birth weight is associated with increased cardiovascular disease (CVD) in humans. Detrimental effects of low birth weight are amplified by rapid catch-up growth. Conversely, slow growth during lactation reduces CVD risk. Gestational protein restriction causes low birth weight, vascular dysfunction, and accelerated aging in rats. Atherosclerotic aortic tissue has shortened telomeres, and oxidative stress accelerates telomere shortening through generation of DNA single-strand breaks (ssbs). This study tested the hypothesis that maternal diet influences aortic telomere length through changes in DNA ssbs, antioxidant capacity, and oxidative stress. We used our models of gestational protein restriction followed by rapid catch-up growth (the recuperated group) and protein restriction during lactation (the postnatal low-protein [PLP] group). Southern blotting revealed fewer aortic DNA ssbs and subsequently fewer short telomeres (P<0.05) in the PLP group. This result was associated with reduced (P<0.01) 8-hydroxy-2-deoxyguanosine, a marker of oxidative stress. PLP animals expressed increased (P<0.01) manganese superoxide-dismutase, copper-zinc superoxide-dismutase, catalase, and glutathione-reductase. Age-dependent changes in antioxidant defense enzymes indicated more protection to oxidative stress in the PLP animals; conversely, recuperated animals demonstrated age-associated impairment of antioxidant defenses. We conclude that maternal diet has a major influence on aortic telomere length. This finding may provide a mechanistic link between early growth patterns and CVD.
Tarry-Adkins JL, Martin-Gronert MS, Chen JH, Cripps RL, Ozanne SE. Maternal diet influences DNA damage, aortic telomere length, oxidative stress, and antioxidant defense capacity in rats. FASEB J. 2008 June Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Box 232, Hills Rd., Cambridge, Cambridgeshire CB2 2QR, UK.