Genetics of extreme human longevity to guide drug discovery for healthy ageing.
Genetics of extreme human longevity to guide drug discovery for healthy ageing.
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DOI：
10.1038/s42255-020-0247-0
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发表时间：
2020-08
影响因子：
20.8
通讯作者：
Vijg J
中科院分区：
文献类型：
--
作者：
Zhang ZD;Milman S;Lin JR;Wierbowski S;Yu H;Barzilai N;Gorbunova V;Ladiges WC;Niedernhofer LJ;Suh Y;Robbins PD;Vijg J
老龄化是最常见的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有关的疾病的一个合乎逻辑的目标。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物干预一直导致线虫、苍蝇和小鼠等多种模式生物的寿命和健康寿命的大幅延长。最近对长寿个体的遗传分析揭示了在这些与长寿显著相关的相同的保守途径中丰富的常见和罕见变异。在这一观点中，我们总结了最近对人类极端长寿遗传学的见解，并建议使用这种罕见的表型来识别遗传变异，作为深入了解健康衰老生理学和开发新疗法以延长人类健康寿命的分子靶点。
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.
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DOI：
10.4161/15384101.2014.950151
发表时间：
2014
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
de Magalhães JP
通讯作者：
de Magalhães JP
影响因子：
17.1
作者：
Finan C;Gaulton A;Kruger FA;Lumbers RT;Shah T;Engmann J;Galver L;Kelley R;Karlsson A;Santos R;Overington JP;Hingorani AD;Casas JP
通讯作者：
Casas JP
影响因子：
30.8
作者：
Chen S;Fragoza R;Klei L;Liu Y;Wang J;Roeder K;Devlin B;Yu H
通讯作者：
Yu H
影响因子：
5.4
作者：
Bitto A;Wang AM;Bennett CF;Kaeberlein M
通讯作者：
Kaeberlein M
影响因子：
13.5
作者：
Dai H;Sinclair DA;Ellis JL;Steegborn C
通讯作者：
Steegborn C