Martin-Gronert Malgorzata S, Tarry-Adkins Jane L, Cripps Roselle L, Chen Jian-Hua, Ozanne Susan E
Department of Clinical Biochemistry, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Am J Physiol Regul Integr Comp Physiol. 2008 Feb;294(2):R494-500. doi: 10.1152/ajpregu.00530.2007. Epub 2007 Dec 19.
Recent findings demonstrate that nutrition during the fetal and neonatal periods can affect the life span of an organism. Our previous studies in rodents using a maternal low protein diet have shown that limiting protein and growth during lactation [postnatal low protein (PLP group)] increases longevity, while in utero growth restriction (IUGR) followed by "catch up growth" (recuperated group) shortens life span. The aim of this study was to investigate mechanisms in early postnatal life that could underlie these substantial differences in longevity. At weaning, PLP animals had improved insulin sensitivity as suggested by lower concentrations of insulin required to maintain concentrations of glucose similar to those of the control group and significant upregulation of insulin receptor-beta, IGF-1 receptor, Akt1, Akt2, and Akt phosphorylated at Ser 473 in the kidney. These animals also had significantly increased SIRT1 (mammalian sirtuin) expression. Expression of the antioxidant enzymes catalase, CuZnSOD, and glutathione peroxidase-1 was elevated in these animals. In contrast, recuperated animals had a significantly increased fasting glucose concentration, while insulin levels remained comparable to those of the control group suggesting relative insulin resistance. MnSOD expression was increased in these animals. These data suggest that early nutrition can lead to alterations in insulin sensitivity and antioxidant capacity very early in life, which may influence life span.
最近的研究结果表明，胎儿期和新生儿期的营养状况会影响生物体的寿命。我们之前在啮齿动物身上进行的研究，采用母体低蛋白饮食，结果显示，哺乳期限制蛋白质摄入和生长（产后低蛋白组）可延长寿命，而子宫内生长受限（IUGR）后出现“追赶生长”（恢复组）则会缩短寿命。本研究的目的是探讨出生后早期可能导致这些寿命显著差异的机制。断奶时，如维持与对照组相似的血糖浓度所需胰岛素浓度较低以及肾脏中胰岛素受体β、IGF-1受体、Akt1、Akt2和丝氨酸473位点磷酸化的Akt显著上调所表明的，PLP动物的胰岛素敏感性有所改善。这些动物的SIRT1（哺乳动物沉默调节蛋白）表达也显著增加。这些动物中抗氧化酶过氧化氢酶、铜锌超氧化物歧化酶和谷胱甘肽过氧化物酶-1的表达升高。相比之下，恢复组动物的空腹血糖浓度显著升高，而胰岛素水平与对照组相当，提示存在相对胰岛素抵抗。这些动物中锰超氧化物歧化酶的表达增加。这些数据表明，早期营养可在生命早期导致胰岛素敏感性和抗氧化能力的改变，这可能会影响寿命。
