Conserved regulators of cognitive aging: From worms to humans

Abstract

Cognitive decline is a major deficit that arises with age in humans. While some research on the underlying causes of these problems can be done in humans, harnessing the strengths of small model systems, particularly those with well-studied longevity mutants, such as the nematode C. elegans, will accelerate progress. Here we review the approaches being used to study cognitive decline in model organisms and show how simple model systems allow the rapid discovery of conserved molecular mechanisms, which will eventually enable the development of therapeutics to slow cognitive aging.

MiR-34 inhibits polycomb repressive complex 2 to modulate chaperone expression and promote healthy brain aging

“…Several genetic manipulations can produce long-lived animals: for example, daf-2 mutations extend lifespan in C. elegans 1 , as does upregulation of a sirtuin in both C. elegans and S. cerevisiae 2 , 3 . Non-genetic interventions also extend lifespan, including caloric restriction and ablation of the reproductive tissue in C. elegans 4 , 5 . Better understanding of mechanisms that confer a healthy brain could lead to insight for treatments for age-associated brain diseases.…”

Beyond Host Defense: Deregulation of Drosophila Immunity and Age-Dependent Neurodegeneration

“…Although the degree of complexity of the mouse brain is lower than that of a human, there are several cellular similarities of the nervous system. They show complex behaviors and are a good tool to measure cognitive changes in neurodegenerative disorders (63).…”

Zebrafish—A Model Organism for Studying the Neurobiological Mechanisms Underlying Cognitive Brain Aging and Use of Potential Interventions

“…Previous studies report significant declines in learning and memory in aged zebrafish. Typically, old zebrafish have less performance on tasks relevant with associative learning, avoidance, spatial learning and working memory (Yu et al, 2006 ; Arey and Murphy, 2017 ; Brock et al, 2017 ). Compared to wild-types, mutants with impaired acetylcholinesterase function had better performance in spatial learning, entrainment and increased rate of learning (Yu et al, 2006 ; Parker et al, 2015 ).…”