Institute of Healthy Ageing and GEE, UCL, London, UK.
Philos Trans R Soc Lond B Biol Sci. 2010 Jan 12;365(1537):147-54. doi: 10.1098/rstb.2009.0222.
Human life expectancy in developed countries has increased steadily for over 150 years, through improvements in public health and lifestyle. More people are hence living long enough to suffer age-related loss of function and disease, and there is a need to improve the health of older people. Ageing is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. This view has been reinforced by the realization that ageing is a disadvantageous trait that evolves as a side effect of mutation accumulation or a benefit to the young, because of the decline in the force of natural selection at later ages. However, important recent discoveries are that mutations in single genes can extend lifespan of laboratory model organisms and that the mechanisms involved are conserved across large evolutionary distances, including to mammals. These mutations keep the animals functional and pathology-free to later ages, and they can protect against specific ageing-related diseases, including neurodegenerative disease and cancer. Preliminary indications suggest that these new findings from the laboratory may well also apply to humans. Translating these discoveries into medical treatments poses new challenges, including changing clinical thinking towards broad-spectrum, preventative medicine and finding novel routes to drug development.
在过去的 150 多年里，通过改善公共卫生和生活方式，发达国家的人类预期寿命稳步提高。因此，越来越多的人长寿到足以遭受与年龄相关的功能丧失和疾病的困扰，有必要改善老年人的健康状况。衰老是一个复杂的损伤积累过程，被认为是实验和医学上难以解决的问题。这种观点因意识到衰老是一种不利的特征而得到加强，这种特征是由于突变积累的副作用或对年轻人的好处而进化而来的，因为自然选择的力量在后期会下降。然而，最近的一些重要发现是，单个基因的突变可以延长实验室模型生物的寿命，并且所涉及的机制在跨越大的进化距离时是保守的，包括对哺乳动物。这些突变使动物在后期保持功能正常且无病理变化，并且它们可以预防特定的与衰老相关的疾病，包括神经退行性疾病和癌症。初步迹象表明，实验室的这些新发现很可能也适用于人类。将这些发现转化为医学治疗带来了新的挑战，包括改变临床思维，转向广谱预防医学，并寻找新的药物开发途径。
