Description:

The Department of Physiology welcomes Dr. Peter Rapp, Senior Investigator & Deputy Lab Chief, with NIH.

Abstract

The nature and severity of brain and cognitive aging vary tremendously across individuals. Although attention has focused predominantly on decline and deterioration as the core dynamics of late life, growing interest centers on the substrates of preserved function. Are these fortunate outcomes simply a consequence of staying young, do they reflect compensation for the deleterious effects of aging, or are other mechanisms at play?  Clinical investigations have been illuminating, but it can be challenging to disentangle the influence of different life course exposures, preclinical neurodegenerative disease processes, and other variables. Our research utilizes animal models of naturally occurring neurocognitive aging that prominently feature increased individual differences, mirroring humans, while allowing exacting experimental control. The findings suggest that, across levels of analysis from expression of molecular markers of plasticity to neural network organization and cognitive strategy selection, positive outcomes in aging are supported by adaptive modifications, in part distinct from the substrates that mediate normal youthful function. Notably, these individual differences in neurocognitive aging appear to influence the response to potential interventions, highlighting the importance of personalized approaches. The encouraging perspective from this area of work is that, alongside a focus on finding ways to slow the fundamental rate of aging, and the critical need for new, effective treatments for neurodegenerative disease, effort might be profitably aimed at testing strategies to promote neuroadaptive trajectories of growing older. An open resource of longitudinal data and biospecimens for animal research on these issues is in development.