The findings offer the first evidence that the activity of the nervous system affects human longevity. Although previous studies had suggested that parts of the nervous system influence aging in animals, the role of neural activity in aging, especially in humans, remained murky.
“An intriguing aspect of our findings is that something as transient as the activity state of neural circuits could have such far-ranging consequences for physiology and life span,”
said study senior author Bruce Yankner, professor of genetics at HMS and co-director of the Paul F. Glenn Center for the Biology of Aging.
IGF Signaling Pathway
The study is based on findings from human brains, mice and worms and suggests that excessive activity in the brain is linked to shorter life spans, while suppressing such overactivity extends life.
Neural excitation appears to act along a chain of molecular events famously known to influence longevity: the insulin and insulin-like growth factor (IGF) signaling pathway.
The key in this signaling cascade appears to be a protein called repressor element 1-silencing transcription (REST), previously shown by the Yankner Lab to protect aging brains from dementia and other stresses.
Neural activity refers to the constant flicker of electrical currents and transmissions in the brain. Excessive activity, or excitation, could manifest in numerous ways, from a muscle twitch to a change in mood or thought, the authors said.
Lifespan Extension Potential
It’s not yet clear from the study whether or how a person’s thoughts, personality or behavior affect their longevity.
“An exciting future area of research will be to determine how these findings relate to such higher-order human brain functions,”
The study could inform the design of new therapies for conditions that involve neural overactivity, such as Alzheimer’s disease and bipolar disorder, the researchers said.
The findings raise the possibility that certain medicines, such as drugs that target REST, or certain behaviors, such as meditation, could extend life span by modulating neural activity. Human variation in neural activity might have both genetic and environmental causes, which would open future avenues for therapeutic intervention, Yankner said.
All Roads Lead To REST
Yankner and colleagues began their investigation by analyzing gene expression patterns – the extent to which various genes are turned on and off – in donated brain tissue from hundreds of people who died at ages ranging from 60 to over 100.
The information had been collected through three separate research studies of older adults. Those analyzed in the current study were cognitively intact, meaning they had no dementia.
Immediately, a striking difference appeared between the older and younger study participants, said Yankner: The longest-lived people, those over 85, had lower expression of genes related to neural excitation than those who died between the ages of 60 and 80.
Next came the question that all scientists confront: correlation or causation? Was this disparity in neural excitation merely occurring alongside more important factors determining life span, or were excitation levels directly affecting longevity?…[ ]