To What Degree is Behavioral Change in Aging Driven by Specific Forms of Neurodegeneration?

To what degree should we expect characteristic changes in behavior observed in the old to have a physical basis in neurodegeneration rather than being an outcome of living in our present cultures for a long time? If the neurodegeneration was prevented or repaired, what behavioral patterns would change, and why? Obviously researchers are a long way from providing defensible answers to those questions, but in this published research the authors provide evidence to suggest that behavioral flexibility is eroded in old age by a physical process, the destruction of a specific class of neuron:

Cholinergic interneurons are rare - they make up just one to two percent of the neurons in the striatum, a key part of the brain involved with higher-level decision-making. Scientists have suspected they play a role in behavioral flexibility, the ability to change strategy when the rules change, and researchers recently confirmed this with experiments. Previous studies tried to identify the role of cholinergic interneurons by recording brain wave activity during behavioral tasks. While that can strongly indicate specific neurons are correlated with a particular behavior, it is not definitive. In this study, researchers killed cholinergic interneurons with a toxin that directly targets them, and then observed how rats reacted to rule changes compared with normal rats with intact neurons. "Our experiments show direct causation, not correlation."

Rats with and without damaged neurons were given tasks for several weeks - they had to press either lever A or B to get a sugar pellet reward. During the first few days, Lever A always resulted in a reward. Both groups of rats had no problem learning the initial strategy to get the sugar pellet - press Lever A. But then, the rules of the game changed. A novel stimulus was introduced - a light flashed above the correct lever, which oscillated between Lever A and B. To get their sugar fix, the rats had to shift strategy and pay attention to this new information. While normal rats quickly responded to the light, rats with damaged neurons could not. The latter group continued to repeat the strategy they had already learned, and were disinclined to explore what the light meant.

"This indicates that cholinergic interneurons throughout the striatum play a common role, namely inhibiting old rules and encouraging exploration, but different regions of the striatum are activated depending on the situation and type of stimulus. Since cholinergic interneurons degenerate with age, this work may provide a clue for understanding the decline in mental flexibility that occurs with advancing age."



There's a lot of scary stuff on this site, but this one is among the scariest.

Neuroscientists or any other cell researchers reading this, whether you're funded by SENS, Calico, the government, or any other institution, whether you agree with the feasibility of anti-aging in general, whether you regularly read this site or don't:

If you like being able to react to circumstances, alter your approach based on available evidence, and/or generally perform the mental tasks that make up critical thinking, find a way to restore the population and function of cholinergic interneurons, before you lose the ability to do that!!

Posted by: Slicer at June 25th, 2015 3:59 PM

Slicer: I wouldn't call it scary at all. The loss of cognitive flexibility with age is an established fact, which should scare you regardless of the mechanism. People criticizing anti-aging efforts sometimes say 'what if we cure aging and are stuck with an eternal society of racists and homophobes and sexists?' because people get stuck in ruts. But this is the best possible result - that a kind of damage which may mimick aging damage causes a similar loss of flexibility. This implies that simply living a long time does not cause beliefs to become incorrigible, it's the damage of aging. Hence, fixing aging will not lead to such a grim future of eternal bigotry.

Posted by: gwern at June 26th, 2015 9:44 AM

Gwern that's a brilliant counter to the old argument of society would become stuck in a rut. I normally say to the person "do you believe everything you did twenty years ago?" They say no and I say of course you don't because ideas and values evolve. The argument is silly and this is clear scientific support that it is.

Posted by: steve h at June 28th, 2015 3:11 AM

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