Purdom Sally, Chen Qin M
Interdisciplinary Graduate Program for Genetics and Genomics, University of Arizona, 1501 N. Campbell, Tucson, AZ 85724, USA.
Trends Mol Med. 2003 May;9(5):206-10. doi: 10.1016/s1471-4914(03)00048-0.
The biology of aging has been mysterious for centuries. Removal of the p66(Shc) gene, which encodes an adaptor protein for cell signaling, extends lifespan by approximately 30% in mice and confers resistance to oxidative stress. The absence of p66(Shc) correlates with reduced levels of apoptosis. Oxidants induce phosphorylation of serine36 on p66(Shc), contributing to inactivation of members of the Forkhead transcription factor family, some of which appear to regulate the expression of antioxidant genes. The expression of p66(Shc) is regulated by the methylation status of its promoter. This leads us to hypothesize that increased methylation of the p66(Shc) promoter might contribute to the absence of its expression and therefore extended longevity in particular individuals.
几个世纪以来，衰老生物学一直很神秘。编码细胞信号转导衔接蛋白的p66(Shc)基因被敲除后，小鼠的寿命可延长约30%，并赋予其对氧化应激的抗性。p66(Shc)缺失与细胞凋亡水平降低相关。氧化剂可诱导p66(Shc)上丝氨酸36磷酸化，导致叉头转录因子家族成员失活，其中一些成员似乎可调节抗氧化基因的表达。p66(Shc)的表达受其启动子甲基化状态的调控。这使我们推测，p66(Shc)启动子甲基化增加可能导致其表达缺失，从而使特定个体的寿命延长。
