Age-associated change in pyruvate metabolism investigated with hyperpolarized 13C-MRI of the human brain

Abstract

In this study, hyperpolarized 13C MRI (HP-13C MRI) was used to investigate changes in the uptake and metabolism of pyruvate with age. Hyperpolarized 13C-pyruvate was administered to healthy aging individuals (N = 35, ages 21–77) and whole-brain spatial distributions of 13C-lactate and 13C-bicarbonate production were measured. Linear mixed-effects regressions were performed to compute the regional percentage change per decade, showing a significant reduction in both normalized 13C-lactate and normalized 13C-bicarbonate production with age: (Figure presented.) per decade for 13C-lactate and (Figure presented.) per decade for 13C-bicarbonate. Certain regions, such as the right medial precentral gyrus, showed greater rates of change while the left caudate nucleus had a flat 13C-lactate versus age and a slightly increasing 13C-bicarbonate versus age. The results show that both the production of lactate (visible as 13C-lactate signal) as well as the consumption of monocarboxylates to make acetyl-CoA (visible as 13C-bicarbonate signal) decrease with age and that the rate of change varies by brain region.