Prolonged exposure to stress may result in deleterious effects to brain function, reducing our cognitive functions, a central aspect required for our daily life. Exposure to stress has been implicated in the acceleration and/or exacerbation of cognitive deficits in elderly subjects, impacting our capacity to learn and remember. A tight control of protein homeostasis (termed proteostasis) is a central factor driving molecular events linked to higher cognitive functions, a process seriously affected during aging. Studies in different model organism point to a decay in the buffering capacity of the proteostasis network as one of the “hallmarks of aging”. Moreover, exacerbated proteostasis dysfunction during aging is suggested as a main driver linked to neurodegenerative diseases such as Alzheimer´s disease. Our group have developed a gene therapy strategy to restore proteostasis in the brain by delivering active transcription factors of the unfolded protein response (UPR) to artificially preserve neuronal function. We hypothesize that chronic stress impairs the proteostasis capacity of the brain, accelerating the cognitive decline associated with aging. We aim to determine the consequences of improving brain proteostasis to aging animals exposed to stressful situations as a strategy to reduce the adverse effect on cognition. This project acquires a central relevance due to the COVID-19 pandemics because of the stress generated by the confinement. Overall, this proposal is the first international attempt to associate environmental stress with brain aging and proteostasis control, aiming to define a novel point of intervention to preserve cognitive function of the elderly and extend healthspan.

http://www.gerochile.org

• Chile

• Older persons
• People with disabilities

The project could be perfectly developed by other groups having the right expertise. We aim to determine the consequences of improving brain proteostasis to aging animals exposed to stressful situations as a strategy to reduce the adverse effect on cognition. This project acquires a central relevance due to the COVID-19 pandemics because of the stress generated by the confinement. Overall, this proposal is the first international attempt to associate environmental stress with brain aging and proteostasis control, aiming to define a novel point of intervention to preserve cognitive function of the elderly and extend healthspan.