Priority Research Paper Volume 12, Issue 11 pp 10041—10058
Lactate dehydrogenase expression modulates longevity and neurodegeneration in Drosophila melanogaster
- 1 Department of Integrative Biology, Oregon State University, Corvallis, OR 97331, USA
- 2 Department of Biology, Western University of London, London N6A 5B7, Ontario, Canada
- 3 OSU NMR Facility, Oregon State University, Corvallis, OR 97331, USA
- 4 Department of Biochemistry and Biophysics, School of Electrical Engineering and Computer Science, Corvallis, OR 97331, USA
- 5 Oregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR 97239, USA
- 6 Present address: Oregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR 97239, USA
Received: April 4, 2020 Accepted: May 14, 2020 Published: June 2, 2020https://doi.org/10.18632/aging.103373
How to Cite
Copyright © 2020 Long et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Lactate dehydrogenase (LDH) catalyzes the conversion of glycolysis-derived pyruvate to lactate. Lactate has been shown to play key roles in brain energetics and memory formation. However, lactate levels are elevated in aging and Alzheimer’s disease patients, and it is not clear whether lactate plays protective or detrimental roles in these contexts. Here we show that Ldh transcript levels are elevated and cycle with diurnal rhythm in the heads of aged flies and this is associated with increased LDH protein, enzyme activity, and lactate concentrations. To understand the biological significance of increased Ldh gene expression, we genetically manipulated Ldh levels in adult neurons or glia. Overexpression of Ldh in both cell types caused a significant reduction in lifespan whereas Ldh down-regulation resulted in lifespan extension. Moreover, pan-neuronal overexpression of Ldh disrupted circadian locomotor activity rhythms and significantly increased brain neurodegeneration. In contrast, reduction of Ldh in neurons delayed age-dependent neurodegeneration. Thus, our unbiased genetic approach identified Ldh and lactate as potential modulators of aging and longevity in flies.