Neuronal-specific proteasome augmentation via Prosß5 overexpression extends lifespan and reduces age-related cognitive decline.
Aging Cell
; 18(5): e13005, 2019 10.
Article
in En
| MEDLINE
| ID: mdl-31334599
ABSTRACT
Cognitive function declines with age throughout the animal kingdom, and increasing evidence shows that disruption of the proteasome system contributes to this deterioration. The proteasome has important roles in multiple aspects of the nervous system, including synapse function and plasticity, as well as preventing cell death and senescence. Previous studies have shown neuronal proteasome depletion and inhibition can result in neurodegeneration and cognitive deficits, but it is unclear if this pathway is a driver of neurodegeneration and cognitive decline in aging. We report that overexpression of the proteasome ß5 subunit enhances proteasome assembly and function. Significantly, we go on to show that neuronal-specific proteasome augmentation slows age-related declines in measures of learning, memory, and circadian rhythmicity. Surprisingly, neuronal-specific augmentation of proteasome function also produces a robust increase of lifespan in Drosophila melanogaster. Our findings appear specific to the nervous system; ubiquitous proteasome overexpression increases oxidative stress resistance but does not impact lifespan and is detrimental to some healthspan measures. These findings demonstrate a key role of the proteasome system in brain aging.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Aging
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Proteasome Endopeptidase Complex
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Drosophila melanogaster
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Cognitive Dysfunction
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Longevity
/
Neurons
Limits:
Animals
Language:
En
Journal:
Aging Cell
Year:
2019
Type:
Article