Age-regulated cycling metabolites are relevant for behavior

Area of Science:

• Chronobiology
• Metabolomics
• Neuroscience

Background:

• Circadian rhythms of sleep, gene expression, and metabolism change with age.
• Little is known about age-related changes in metabolic cycles and their role in regulating behavioral cycles.

Purpose of the Study:

• To investigate age-related variations in metabolite cycling in Drosophila.
• To determine if manipulating the pentose phosphate pathway (PPP) affects sleep-wake cycles.

Main Methods:

• Compared metabolite cycling in young and old Drosophila heads using JTK analysis.
• Measured 159 metabolites.
• Overexpressed glucose-6-phosphate dehydrogenase (G6PD) in circadian clock neurons.

Main Results:

• Significant age-related variations in metabolite cycling were observed.
• Cycling metabolites in young and old flies were largely distinct (only 4 overlapped).
• Overexpression of G6PD decreased sleep and increased cellular calcium and mitochondrial oxidation.

Conclusions:

• Metabolic cycles change significantly with age, with distinct cycling metabolites in young and old flies.
• Pentose phosphate pathway (PPP) activity influences neuronal activity and sleep-wake cycles.
• Metabolic regulation is crucial for maintaining neural activity and sleep patterns.