Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila.
iScience
; 24(1): 101979, 2021 Jan 22.
Article
in En
| MEDLINE
| ID: mdl-33490892
ABSTRACT
Brain neurons play a central role in organismal aging, but there is conflicting evidence about the role of neuronal glucose availability because glucose uptake and metabolism are associated with both aging and extended life span. Here, we analyzed metabolic changes in the brain neurons of Drosophila during aging. Using a genetically encoded fluorescent adenosine triphosphate (ATP) biosensor, we found decreased ATP concentration in the neuronal somata of aged flies, correlated with decreased glucose content, expression of glucose transporter and glycolytic enzymes and mitochondrial quality. The age-associated reduction in ATP concentration did not occur in brain neurons with suppressed glycolysis or enhanced glucose uptake, suggesting these pathways contribute to ATP reductions. Despite age-associated mitochondrial damage, increasing glucose uptake maintained ATP levels, suppressed locomotor deficits, and extended the life span. Increasing neuronal glucose uptake during dietary restriction resulted in the longest life spans, suggesting an additive effect of enhancing glucose availability during a bioenergetic challenge on aging.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
IScience
Year:
2021
Document type:
Article
Affiliation country:
Japón