Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower St, London WC1E 6BT, UK.
Curr Biol. 2012 Sep 11;22(17):R741-52. doi: 10.1016/j.cub.2012.07.024.
Age is the main risk factor for the prevalent diseases of developed countries: cancer, cardiovascular disease and neurodegeneration. The ageing process is deleterious for fitness, but can nonetheless evolve as a consequence of the declining force of natural selection at later ages, attributable to extrinsic hazards to survival: ageing can then occur as a side-effect of accumulation of mutations that lower fitness at later ages, or of natural selection in favour of mutations that increase fitness of the young but at the cost of a higher subsequent rate of ageing. Once thought of as an inexorable, complex and lineage-specific process of accumulation of damage, ageing has turned out to be influenced by mechanisms that show strong evolutionary conservation. Lowered activity of the nutrient-sensing insulin/insulin-like growth factor/Target of Rapamycin signalling network can extend healthy lifespan in yeast, multicellular invertebrates, mice and, possibly, humans. Mitochondrial activity can also promote ageing, while genome maintenance and autophagy can protect against it. We discuss the relationship between evolutionarily conserved mechanisms of ageing and disease, and the associated scientific challenges and opportunities.
年龄是发达国家常见疾病（癌症、心血管疾病和神经退行性疾病）的主要风险因素。衰老过程对健康是有害的，但它也可以作为自然选择在后期力量下降的结果而进化，这归因于生存的外在危险：衰老可以作为降低后期健康适应性的突变积累的副作用发生，也可以作为有利于增加年轻人适应性但代价是随后更高的衰老速度的突变的自然选择而发生。衰老曾经被认为是一种不可避免的、复杂的、特定谱系的损伤积累过程，但事实证明，它受到了具有强大进化保守性的机制的影响。营养感应胰岛素/胰岛素样生长因子/雷帕霉素靶蛋白信号网络活性的降低可以延长酵母、多细胞无脊椎动物、老鼠，甚至可能是人类的健康寿命。线粒体活性也可以促进衰老，而基因组维护和自噬可以防止衰老。我们讨论了衰老的进化保守机制与疾病之间的关系，以及相关的科学挑战和机遇。
