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

Mechanisms underlying longevity: A genetic switch model of aging.

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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. Electronic address:


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.


Aging; Epigenetics; Genetics; Lifespan; Theory

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