title: Coenzyme Q10 prevents accelerated cardiac aging in a rat model of poor maternal nutrition and accelerated postnatal growth.
abstract: Studies in human and animals have demonstrated that nutritionally induced low birth-weight followed by rapid postnatal growth increases the risk of metabolic syndrome and cardiovascular disease. Although the mechanisms underlying such nutritional programming are not clearly defined, increased oxidative-stress leading to accelerated cellular aging has been proposed to play an important role. Using an established rodent model of low birth-weight and catch-up growth, we show here that post-weaning dietary supplementation with coenzyme Q10, a key component of the electron transport chain and a potent antioxidant rescued many of the detrimental effects of nutritional programming on cardiac aging. This included a reduction in nitrosative and oxidative-stress, telomere shortening, DNA damage, cellular senescence and apoptosis. These findings demonstrate the potential for postnatal antioxidant intervention to reverse deleterious phenotypes of developmental programming and therefore provide insight into a potential translatable therapy to prevent cardiovascular disease in at risk humans.
authors: University of Cambridge, Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust - MRC Institute of Metabolic Science, Level 4, Box 289, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 OQQ, UK.
authors: Jane L
authors: JL
authors: Tarry-Adkins
authors: Heather L
authors: HL
authors: Blackmore
authors: Malgorzata S
authors: MS
authors: Martin-Gronert
authors: Denise S
authors: DS
authors: Fernandez-Twinn
authors: Josie M
authors: JM
authors: McConnell
authors: Iain P
authors: IP
authors: Hargreaves
authors: Dino A
authors: DA
authors: Giussani
authors: Susan E
authors: SE
authors: Ozanne
keywords: 3-NT, 3-nitrotyrosine; 4-HNE, 4-hydroxynonenal; BER, base excision repair; Bax, Bcl2-associated protein; CAST, computer assisted stereology toolbox.; CVD, cardiovascular disease; Cellular senescence; CoQ, coenzyme Q; CuZnSOD, copper-zinc superoxide dismutase; DIG, dioxygenin; DNA damage; Developmental programming; ETC, electron transport chain; GPx, glutathione peroxidase; GR, glutathione reductase; MnSOD, manganese superoxide dismutase; NEIL1, nei endonuclease VIII-like 1; NOX, nicotinamide adenine dinucleotide diphosphate oxidase; NTHL1, Nthl endonuclease III like-1; O2, superoxide anion; OGG-1, 8 oxoguanine DNA glycosylase 1; OH-, hydroxy radicals; Oxidative-stress; PGFE, pulsed field gel electrophoresis; PRDX, peroxidiredoxin; RIS, reactive inflammatory species; RNS, reactive nitrogen species; ROS, reactive oxidative species; Telomere length; Ubiquinone; XO, xanthine oxidase; acta1, sarco endoplasmic reticulum Ca(2+) ATPase; actin, alpha-1; nppa, natriuretic peptide A; nppb, natriuretic peptide B; serca2, single strand breaks, SSBs