University of Cambridge Metabolic Research Laboratories and Medical Research Council (MRC) Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge, United Kingdom.
FASEB J. 2019 Jan;33(1):239-253. doi: 10.1096/fj.201701350RR. Epub 2018 Jul 5.
Reduced fetal nutrition and rapid postnatal growth accelerates the aging phenotype in many organ systems; however, effects on the immune system are unclear. We addressed this by studying the thymus from a rat model of developmental programming. The recuperated group was generated by in utero protein restriction, followed by cross-fostering to control-fed mothers, and were then compared with controls. Fat infiltration and adipocyte size increased with age ( P < 0.001) and in recuperated thymi ( P < 0.05). Cortex/medulla ratio decreased with age ( P < 0.001) and decreased ( P < 0.05) in 12-mo recuperated thymi. Age-associated decreases in thymic-epithelial cell ( P < 0.01) and thymocyte markers ( P < 0.01) were observed in both groups and was decreased ( P < 0.05) in recuperated thymi. These data demonstrate effects of developmental programming upon thymic involution. The recuperated group had longer thymic telomeres than controls ( P < 0.001) at 22 d and at 3 mo, which was associated with increased expression of telomere-length maintenance molecules [telomerase RNA component ( Terc; P < 0.01), P23 ( P = 0.02), and Ku70 and Ku80 ( P < 0.01)]. By 12 mo, recuperated offspring had shorter thymic telomeres than controls had ( P < 0.001) and reduced DNA damage-response markers [( DNA-PKcs, Mre11 ( P < 0.01), Xrcc4 ( P = 0.02), and γ-H2ax ( P < 0.001], suggesting failure of earlier compensatory responses. Our results suggest that low birth weight with rapid postnatal growth results in premature thymic maturation, resulting in accelerated thymic aging. This could lead to increased age-associated vulnerability to infection.-Tarry-Adkins, J. L., Aiken, C. E., Ashmore, T. J., Fernandez-Twinn, D. S., Chen, J.-H., Ozanne, S. E. A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats.
胎儿营养减少和快速的产后生长加速了许多器官系统的衰老表型；然而，其对免疫系统的影响尚不清楚。我们通过研究发育编程大鼠模型的胸腺来解决这个问题。恢复组是通过宫内蛋白质限制产生的，然后被交叉寄养到喂养对照组的母亲，然后与对照组进行比较。脂肪浸润和脂肪细胞大小随年龄增长而增加（P<0.001），在恢复组的胸腺中也增加（P<0.05）。皮质/髓质比值随年龄下降（P<0.001），在 12 个月的恢复组胸腺中下降（P<0.05）。在两组中都观察到与年龄相关的胸腺上皮细胞（P<0.01）和胸腺细胞标志物（P<0.01）的减少，在恢复组的胸腺中减少更为明显（P<0.05）。这些数据表明发育编程对胸腺萎缩有影响。与对照组相比，恢复组的胸腺端粒更长（P<0.001），在 22 天和 3 个月时，这与端粒长度维持分子[端粒酶 RNA 成分（Terc；P<0.01）、P23（P=0.02）和 Ku70 和 Ku80（P<0.01）]的表达增加有关。到 12 个月时，恢复组的后代的胸腺端粒比对照组短（P<0.001），并且减少了 DNA 损伤反应标志物[DNA-PKcs、Mre11（P<0.01）、Xrcc4（P=0.02）和γ-H2ax（P<0.001）]，表明早期补偿反应失败。我们的结果表明，低出生体重与快速的产后生长导致过早的胸腺成熟，从而加速胸腺衰老。这可能导致与年龄相关的感染易感性增加。-Tarry-Adkins，J. L.，Aiken，C. E.，Ashmore，T. J.，Fernandez-Twinn，D. S.，Chen，J.-H.，Ozanne，S. E. 一种不佳的母体饮食与加速的产后生长相结合，会导致雄性大鼠胸腺的衰老特征发生改变。
