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Neural activity that plays role in aging discovered

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Researchers discover that neural activity in the brain plays a key role in both lifespan and the aging process.

The brain is always busy; trillions of electrical signals are relayed from neuron to neuron to neuron, through a network that is never switched off. Harvard researchers have been unlocking the intricacies of a signalling cascade that can influence Longevity – and they have discovered a key protein is involved.

We spoke to the study’s senior author Bruce Yankner, professor of genetics at Harvard Medical School and co-director of the Paul F Glenn Center for the Biology of Aging, who told us: “The idea that neural circuit activity in the brain can have far-reaching effects on lifespan is exciting, and raises the possibility of a previously unanticipated mode of regulation of the aging process.”

Longevity Technology: This news gives us excitations … and it’s partly because this research involved human brains, meaning any progress to human clinical trials will be accelerated. Mapping out the role of the REST protein could lead to new anti-aging therapies or drugs.

The TRL score for this Longevity.Technology domain is currently set at:

The TRL score for the technology addressed in this article is: “Early proof of concept demonstrated in the laboratory.”

The scientists at Harvard Medical School studied hundreds of human brains that had been donated to science, examining the brains of dementia-free older adults who had died between 60 and 100.The brains in the upper age range of the sample (85 to 100 years old) were found to have significantly less expression of the genes that are linked to neural overactivity when compared with those from the younger age range (60 to 80 years old).

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Of particular interest was the discovery that the older brains also shared more of one component than the brains of those who had died younger: a protein called REST (RE1-Silencing Transcription factor). REST plays an important role in repressing the neural genes of non-neuronal cells [1], but this powerful protein also protects the brain from stress and dementia as we age [2].

The study, published in Nature, is also based on research on mice and worms, and suggests that the activity of the nervous system affects our Longevity. Neural excitation appears to progress down a chain of molecular events that are closely linked to Longevity [3]: the insulin and insulin-like growth factor (IGF) signaling pathways. The research suggests that excessive excitation in the brain is linked to shorter life spans, while suppressing such over-activity — demonstrated by the greater prevalence of the REST protein — actually extends life. The REST protein was shown to lower excitation, suppressing the genes involved in neural excitation, including neurotransmitter receptors, ion channels and the structural components of synapses.

The researchers’ work on animal models showed that, when REST was blocked, there was higher neural activity and consequently earlier deaths. However, when the amount of REST was boosted, there was an opposite effect: lower neural activity and death at a later age [4].

There is still some way to go in this research and Yankner shed some light on the next steps for his team: “We are interested in how neural activity interfaces with the insulin/IGF signalling pathway to regulate lifespan, and particularly the role of the REST transcription factor. We are also screening potential drugs that elevate REST function as a potential therapeutic approach to Alzheimer’s disease.”

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This area of Longevity research is of great interest, as Yankner explained: “REST acts on the epigenome, the set of modifications to our DNA and associated proteins that do not involve changes in the DNA code. There is a considerable research effort focused on the role of the epigenome in aging, and whether epigenomic changes underlie degenerative changes associated with aging.”

[1] https://www.genecards.org/cgi-bin/carddisp.pl?gene=REST
[2] https://www.ncbi.nlm.nih.gov/pubmed/24670762
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295030/
[4] https://bit.ly/2CiPpK1

Image: Geralt Pixibay
Eleanor Garth
Deputy Editor Now a science and medicine journalist, Eleanor worked as a consultant for university spin-out companies and provided research support at Imperial College London and various London hospitals in a former life.
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