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Chapter 3 - Cellular and Molecular Mechanisms for Age-Related Cognitive Decline

Published online by Cambridge University Press:  30 November 2019

Kenneth M. Heilman
Affiliation:
University of Florida
Stephen E. Nadeau
Affiliation:
University of Florida
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Summary

Aging is often associated with a progressive decline of cognitive functions, due in part to the susceptibility of specific brain regions to stressors of aging. However, chronological age is a poor predictor of cognition. Cognitive decline is variable in terms of onset and progression, suggesting that biological age, due to differences in biological mechanisms that regulate vulnerability, is a better predictor of cognitive decline. As with humans, animal models exhibit variability in age-related cognitive decline, and this variability has been employed to determine biomarkers and mechanisms of cognitive impairment. Based on these animal models, theories of age-related cognitive decline have evolved. Recent work has focused on senescent physiology, rather than cell death associated with neurodegenerative disease. The results suggest that age-related alterations in redox stress modify Ca2+ regulation to alter learning and memory mechanisms, as well as signaling cascades from the synapse to the nucleus. Furthermore, the stressors of aging, senescent physiology, and environmental factors interact with epigenetic mechanisms contributing variability in gene transcription, resulting in variability in resiliency, onset, and the progression of the aging phenotype.

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Publisher: Cambridge University Press
Print publication year: 2019

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