Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
Mech Ageing Dev. 2011 Jan-Feb;132(1-2):72-3. doi: 10.1016/j.mad.2010.11.004. Epub 2010 Dec 21.
A recent study by Kawahara and Kono (2010) reports that mice artificially produced with two sets of female genomes have an increased average lifespan of 28%. Moreover, these animals exhibit a smaller body size, a trait also observed in several other long-lived mouse models. One hypothesis is that alterations in the expression of paternally methylated imprinted genes are responsible for the life-extension of bi-maternal mice. Considering the similarities in postnatal growth retardation between mice with mutations in the Rasgrf1 imprinted gene and bi-maternal mice, Rasgrf1 is the most likely culprit for the low body weight and extended lifespan of bi-maternal mice. Rasgrf1 is a neuronal guanine-nucleotide exchange factor that induces Ras signaling in a calcium-dependent manner and has been implicated in learning and memory. Like other long-lived mouse strains, Rasgrf1 mutants are known to have low growth hormone and IGF-1 levels and the Rasgrf1 yeast homolog CDC25 had been previously associated with lifespan. Therefore, although the evidence is not conclusive, it does point towards the involvement of Rasgrf1 in the regulation of longevity, hypothetically through a mechanism similar to that observed in other long-lived mice of low GH/IGF-1 signaling causing a low body weight and life-extension.
最近，川原和河野（2010）的一项研究报告称，人工产生两套雌性基因组的老鼠的平均寿命延长了 28%。此外，这些动物的体型较小，这一特征也在其他几种长寿老鼠模型中观察到。一种假设是，父源甲基化印记基因表达的改变导致了双母鼠的寿命延长。考虑到 Rasgrf1 印记基因发生突变的老鼠和双母鼠在出生后生长迟缓方面的相似性，Rasgrf1 很可能是双母鼠体重低和寿命延长的罪魁祸首。Rasgrf1 是一种神经元鸟嘌呤核苷酸交换因子，以钙依赖的方式诱导 Ras 信号转导，并与学习和记忆有关。与其他长寿鼠种一样，Rasgrf1 突变体已知生长激素和 IGF-1 水平较低，Rasgrf1 的酵母同源物 CDC25 先前与寿命有关。因此，尽管证据还不确凿，但它确实表明 Rasgrf1 参与了长寿的调控，假设通过类似于其他低 GH/IGF-1 信号长寿老鼠的机制，导致体重低和寿命延长。
