Genetics: REST protein linked to long life

Overall levels of neural activity in the brain, mediated by a protein called REST, may influence lifespan, suggests a Nature study. The finding, based on various studies in model organisms and humans, could assist researchers seeking new approaches to slow ageing in humans.

Previous studies have suggested that the nervous system has a role in the regulation of ageing, but the mechanisms underpinning this relationship have been hard to define. Bruce Yankner and colleagues studied patterns of gene expression in post-mortem human brain tissue and found that genes related to neural excitation and synaptic function are downregulated in long-lived individuals (who were at least 85 years old).

Turning to model organisms, they found that they could extend the lifespan of nematode worms by lowering levels of neural excitement and synaptic activity in the brain using drugs or genetic manipulations. Increasing levels of neural activity had the opposite effect. This finding suggests a causal link between lifespan and patterns of neural activity.

The central nervous system is full of excitatory and inhibitory neurons that increase and decrease synaptic activity, respectively. The authors think that an imbalance in the overall levels of excitement and inhibition may contribute to the ageing process, and highlight the role of a mammalian transcription factor called REST, which dampens neural activity. Strategies that boost REST levels and reduce excitatory neural activity could be used to influence ageing, they suggest.

doi:10.1038/s41586-019-1647-8

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