High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio

• DOI: 10.1073/pnas.1008189107
• Publication Date: 2010-11-02T05:22:00Z
• Authors: Jaime M. Ross; Johanna Öberg; Stefan Brené; Giuseppe Coppotelli; Mügen Terzioglu; Karin Pernold; Michel Goiny; Rouslan Sitnikov; Jan Kehr; Aleksandra Trifun...; Nils-Göran Larsson; Barry J. Hoffer; Lars Olson
• Keywords: Lactate dehydrogenase A

At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely mutator mice establish a molecular link between mitochondrial dysfunction abnormal metabolism process. Using proton magnetic resonance spectroscopy HPLC, found that brain lactate levels were increased twofold both during To correlate striking increase with tissue pathology, investigated respiratory chain enzymes detected failure key areas from mice. We situ hybridization show caused by shift transcriptional activities dehydrogenases promote pyruvate conversion. Separation five tetrameric dehydrogenase (LDH) isoenzymes revealed an those dominated Ldh-A product decrease rich Ldh-B product, which, turn, increases Spectrophotometric assays measuring LDH activity sides reaction showed higher → brain. argue for use as noninvasive strategy monitoring this hallmark The mouse allows us conclude LDH-A/LDH-B ratio causes high levels, predictive phenotypes.