Institute of Healthy Ageing, London, WC1E 6BT, UK.
Exp Gerontol. 2011 May;46(5):376-81. doi: 10.1016/j.exger.2010.09.003. Epub 2010 Sep 16.
A remarkable discovery of recent years is that, despite the complexity of ageing, simple genetic interventions can increase lifespan and improve health during ageing in laboratory animals. The pathways involved have often proved to sense nutrients and to match costly activities of organisms, such as growth, metabolism and reproduction, to nutrient status. For instance, the insulin/insulin-like growth factor and Target of Rapamycin signalling network has proved to play a function in ageing, from yeast to mammals, seemingly including humans. In the fruit fly Drosophila, altered activity of several components of this network can increase lifespan and improve locomotor and cardiac function during ageing. The fly brain, fat body (equivalent of mammalian liver and white adipose tissue) and the germ line are important in determination of lifespan, with considerable communication between different tissues. Cellular detoxification pathways, increased autophagy and altered protein synthesis have all been implicated in increased lifespan from reduced IIS/TOR activity, with the role of defence against oxidative stress unresolved. Reduced IIS/TOR signalling can alter or block the response of lifespan to dietary restriction. Reduced IIS can act acutely to lower death rate, implying that it may ameliorate the effects of ageing-related damage, rather than preventing it.
近年来的一项重大发现是，尽管衰老过程复杂，但简单的遗传干预可以延长实验动物的寿命并改善衰老过程中的健康状况。所涉及的途径通常被证明可以感知营养物质，并使生物体的昂贵活动（如生长、代谢和繁殖）与营养状况相匹配。例如，胰岛素/胰岛素样生长因子和雷帕霉素靶蛋白信号网络已被证明在从酵母到哺乳动物的衰老过程中发挥作用，似乎包括人类。在果蝇中，改变该网络的几个组成部分的活性可以延长寿命并改善衰老过程中的运动和心脏功能。蝇脑、脂肪体（相当于哺乳动物的肝脏和白色脂肪组织）和生殖系在寿命决定中很重要，不同组织之间有大量的通讯。细胞解毒途径、自噬增加和蛋白质合成改变都与降低 IIS/TOR 活性导致寿命延长有关，而氧化应激防御的作用仍未解决。降低 IIS/TOR 信号可以改变或阻止寿命对饮食限制的反应。降低的 IIS 可以急性地降低死亡率，这意味着它可能减轻与衰老相关的损伤的影响，而不是预防它。
