Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen AB24 2TZ, UK.
Philos Trans R Soc Lond B Biol Sci. 2011 Jan 12;366(1561):99-107. doi: 10.1098/rstb.2010.0243.
Over the last two centuries, there has been a significant increase in average lifespan expectancy in the developed world. One unambiguous clinical implication of getting older is the risk of experiencing age-related diseases including various cancers, dementia, type-2 diabetes, cataracts and osteoporosis. Historically, the ageing process and its consequences were thought to be intractable. However, over the last two decades or so, a wealth of empirical data has been generated which demonstrates that longevity in model organisms can be extended through the manipulation of individual genes. In particular, many pathological conditions associated with the ageing process in model organisms, and importantly conserved from nematodes to humans, are attenuated in long-lived genetic mutants. For example, several long-lived genetic mouse models show attenuation in age-related cognitive decline, adiposity, cancer and glucose intolerance. Therefore, these long-lived mice enjoy a longer period without suffering the various sequelae of ageing. The greatest challenge in the biology of ageing is to now identify the mechanisms underlying increased healthy lifespan in these model organisms. Given that the elderly are making up an increasingly greater proportion of society, this focused approach in model organisms should help identify tractable interventions that can ultimately be translated to humans.
在过去的两个世纪中，发达国家的平均预期寿命显著延长。随着年龄增长，一个明确的临床后果是患上与年龄相关的疾病的风险增加，包括各种癌症、痴呆症、2 型糖尿病、白内障和骨质疏松症。从历史上看，衰老过程及其后果被认为是难以解决的。然而，在过去的二十年左右，大量的经验数据表明，通过操纵单个基因，可以延长模式生物的寿命。特别是，许多与模式生物衰老过程相关的病理状况，从线虫到人类都得到了很好的保守，在长寿的基因突变体中得到了缓解。例如，几种长寿的遗传小鼠模型表现出与年龄相关的认知能力下降、肥胖、癌症和葡萄糖不耐受的缓解。因此，这些长寿的老鼠可以在更长的时间内免受各种衰老的影响。衰老生物学中最大的挑战是现在要确定这些模式生物中健康寿命延长的机制。鉴于老年人在社会中所占的比例越来越大，这种针对模式生物的集中方法应该有助于确定可行的干预措施，最终可以转化为人类。
