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The Fountain of Youth: Brain Excitation Linked to Longevity

Picture
Angela Wang
​Edited by Chelsea Le

January 5 2020
Research
Modern medicine, having successfully constrained the threat posed to humans by most parasitic diseases, is now commonly faced with questions on how to improve human life expectancy. Why do some people live longer than others? How do certain brain disorders develop? While common reasons include lifestyle choices like diet and exercise or socioeconomic factors such as income, recent research conducted by the Harvard Medical School indicates a possible link between brain activity and a person’s lifespan. Specifically, researchers have identified a transcription factor called REST, whose presence or absence leads to higher or lower levels of neuron activity, respectively.

Transcription factors are proteins that influence how genes are expressed, and thus affect the level of activity associated with those genes. Through several series of experiments, the researchers were able to determine the role that REST played in organismal longevity. Researchers pinpointed the gene associated with REST by comparing the RNA sequences of deceased individuals of all ages. They discovered a significant difference in the activation of excitatory genes between individuals under 80 years old and over 85 years old. They also observed more REST in neurons of individuals over 85.
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Scientists used nematodes as a test organism for their experiments on the REST transcription factor.
Image Source: AKK 8-004 #3 Burrowing nematode 7880 (2) Tridate Khaithong photo by Scot Nelson
​
Is licensed under Public Domain Mark 1.0 
From there, researchers conducted further experiments in organisms such as flatworms and mice to determine how REST affected the excitation of neurons. By mutating the REST gene in C. elegans, a species of flatworm, researchers found that less REST resulted in greater neural activity and shorter lifespans when compared to flatworms with normal levels of REST. By mutating different parts of the transcription factor’s gene sequence, researchers elucidated that REST acts on genes controlling ion channels and neurotransmitter receptors in neurons, which play an important role in exciting the brain. Additionally, researchers learned that due to REST’s suppression of brain activity, another group of genes called FOX genes, became more active. These genes code for proteins that positively affect longevity through insulin and insulin growth factor pathways. By modifying the REST gene expression, researchers discovered that the effects on longevity appeared to be bidirectional: more REST in the brain led to a longer lifespan, while less REST led to a shorter lifespan.

While still in its early stages, this research has great potential for both extending human lifespans and uncovering potential treatment pathways for brain diseases, such as Alzheimer’s disease and bipolar disorder, which result from neuronal overexcitation. Since the REST transcription factor “calms” the brain, treatments that increase the amount or efficacy of REST proteins may help those who suffer from such diseases.
​Featured Image Source: Alina Grubnyak

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