Ageing is the greatest risk factor for most common chronic human diseases, and it therefore is a logical target for developing interventions to prevent, mitigate or reverse multiple age-related morbidities. Over the past two decades, genetic and pharmacologic interventions targeting conserved pathways of growth and metabolism have consistently led to substantial extension of the lifespan and healthspan in model organisms as diverse as nematodes, flies and mice. Recent genetic analysis of long-lived individuals is revealing common and rare variants enriched in these same conserved pathways that significantly correlate with longevity. In this Perspective, we summarize recent insights into the genetics of extreme human longevity and propose the use of this rare phenotype to identify genetic variants as molecular targets for gaining insight into the physiology of healthy ageing and the development of new therapies to extend the human healthspan.

衰老是大多数常见人类慢性疾病的最大风险因素，因此它是制定干预措施以预防、减轻或逆转多种与年龄相关的疾病的合理目标。在过去的二十年中，针对保守的生长和代谢途径的遗传和药理学干预措施一直导致线虫、苍蝇和小鼠等多种模式生物的寿命和健康寿命显着延长。最近对长寿个体的遗传分析揭示了常见和罕见的变异，这些变异富含这些与长寿显着相关的相同保守途径。在这个观点中，