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.
Mol Metab. 2013 Sep 27;2(4):480-90. doi: 10.1016/j.molmet.2013.09.004. eCollection 2013.
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.
在人类和动物研究中已经证实,营养性低出生体重继而快速的出生后生长会增加代谢综合征和心血管疾病的风险。虽然这种营养编程的机制尚未明确界定,但有人提出,导致细胞加速衰老的氧化应激增加可能起重要作用。我们采用已建立的低出生体重和追赶性生长的啮齿动物模型,在这里表明,在断奶后饮食中补充辅酶 Q10(电子传递链的关键组成部分和有效的抗氧化剂)可以挽救营养编程对心脏老化的许多有害影响。这包括减少硝化和氧化应激、端粒缩短、DNA 损伤、细胞衰老和细胞凋亡。这些发现表明,出生后抗氧化干预有可能逆转发育编程的有害表型,从而为预防高危人群心血管疾病的潜在可转化治疗提供了新的见解。