Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila
Mikiko Oka,
Emiko Suzuki,
Akiko Asada,
Taro Saito,
Koichi M. Iijima,
Kanae Ando
Affiliations
Mikiko Oka
Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan
Emiko Suzuki
Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan; Gene Network Laboratory, National Institute of Genetics, Mishima, Shizuoka, Japan; Department of Genetics, SOKENDAI, Mishima, Shizuoka, Japan
Akiko Asada
Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan; Department of Biological Sciences, Faculty of Science, Tokyo Metropolitan University, Tokyo, Japan
Taro Saito
Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan; Department of Biological Sciences, Faculty of Science, Tokyo Metropolitan University, Tokyo, Japan
Koichi M. Iijima
Department of Alzheimer's Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan; Department of Experimental Gerontology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan
Kanae Ando
Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan; Department of Biological Sciences, Faculty of Science, Tokyo Metropolitan University, Tokyo, Japan; Corresponding author
Summary: 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.
