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衰老的内在机制:一种遗传开关模型。

Mechanisms underlying longevity: A genetic switch model of aging.

机构信息

Laboratory of Aging and Neurodegenerative Disease (LAND), Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Metabolic Disorders and Complications Program, Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.

出版信息

Exp Gerontol. 2018 Jul 1;107:136-139. doi: 10.1016/j.exger.2017.08.005. Epub 2017 Aug 7.

Abstract

While the questions of "What causes aging?" and "Why do we age?" and "How can we stop it?" remain unanswered, recent advances in aging research have continued to increase our understanding of the aging process. Until the last couple of decades, aging was viewed as an inevitable process of damage accumulation and not a subject for scientific pursuit. This view changed when it was demonstrated that the aging process is in fact malleable and genetically determined: mutations in single genes can have dramatic effects on longevity. Despite the rapid advancement of our knowledge about aging, the cause of aging remains unclear. In this paper, experiments demonstrating the roles of genetics and epigenetics in modulating longevity are reviewed, concluding with a new model of aging. This genetic switch model of aging proposes that aging is caused by a genetically-programmed turning off of survival and maintenance pathways after reproduction finishes leading to a progressive functional decline. If this model is correct, it may be possible to extend lifespan and healthspan by identifying the molecular pathways involved and simply turning the switch back on.

摘要

虽然“什么导致衰老?”“我们为什么会衰老?”“我们如何阻止它?”这些问题仍未得到解答,但衰老研究的最新进展不断增加我们对衰老过程的理解。直到过去几十年,衰老才被视为一种不可避免的损伤积累过程,而不是科学追求的主题。当证明衰老过程实际上是可塑的和由基因决定的时,这种观点发生了变化:单个基因突变会对寿命产生巨大影响。尽管我们对衰老的了解迅速发展,但衰老的原因仍不清楚。在本文中,回顾了证明遗传学和表观遗传学在调节寿命中的作用的实验,最后提出了一个新的衰老模型。这个遗传开关衰老模型提出,衰老的原因是生殖完成后,生存和维持途径被基因编程关闭,导致功能逐渐衰退。如果这个模型是正确的,那么通过确定涉及的分子途径并简单地将开关重新打开,可能延长寿命和健康寿命。

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