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Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):2876-81. doi: 10.1073/pnas.1417921112. Epub 2015 Feb 17.

In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences.

Author information

1
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455 zhu@cmrr.umn.edu wei@cmrr.umn.edu.
2
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455.

Abstract

NAD is an essential metabolite that exists in NAD(+) or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD(+)/NADH redox state and modulating cellular signaling processes through the activity of the NAD(+)-dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD(+) and NADH contents and the NAD(+)/NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD(+), total NAD contents, and NAD(+)/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ.

KEYWORDS:

NAD; aging; human brain; in vivo 31P MR spectroscopy; redox state

PMID:
25730862
PMCID:
PMC4352772
DOI:
10.1073/pnas.1417921112
[Indexed for MEDLINE]
Free PMC Article

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