Cognitive aging as an extension of brain development: a model linking learning, brain plasticity, and neurodegeneration

Abstract

Differences in cognitive aging rates among mammals suggest that the pace of brain aging is genetically determined. In this work, we investigate the possibility that brain aging is an extension of brain development. It is possible that a subset of developmental mechanisms are extreme cases of antagonistic pleiotropy in that they are necessary for reaching adulthood and yet later cause age-related diseases. We derive a model linking development and brain aging in which childhood events essential for brain development later result in neurodegeneration. The hypothesis presented herein involves brain plasticity in which the same mechanisms that shape the adult phenotype continue at later ages contributing to cognitive dysfunction and eventually dementia. The same genetic program that decreases brain plasticity at early ages to focus our mind to the surrounding environment may continue in adulthood resulting in cognitive aging. Experimental implications for understanding neurodegeneration in this context are also discussed.