Beta-lapachone, a modulator of NAD metabolism, prevents health declines in aged mice

PLoS One. 2012;7(10):e47122. doi: 10.1371/journal.pone.0047122. Epub 2012 Oct 11.

Abstract

NADH-quinone oxidoreductase 1 (NQO1) modulates cellular NAD(+)/NADH ratio which has been associated with the aging and anti-aging mechanisms of calorie restriction (CR). Here, we demonstrate that the facilitation of NQO1 activity by feeding β-lapachone (βL), an exogenous NQO1 co-substrate, prevented age-dependent decline of motor and cognitive function in aged mice. βL-fed mice did not alter their food-intake or locomotor activity but did increase their energy expenditure as measured by oxygen consumption and heat generation. Mitochondrial structure and numbers were disorganized and decreased in the muscles of control diet group but those defects were less severe in βL-fed aged mice. Furthermore, for a subset of genes associated with energy metabolism, mice fed the βL-diet showed similar changes in gene expression to the CR group (fed 70% of the control diet). These results support the potentiation of NQO1 activity by a βL diet and could be an option for preventing age-related decline of muscle and brain functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects*
  • Aging / physiology
  • Animals
  • Behavior, Animal / drug effects
  • Body Weight / drug effects
  • Caloric Restriction
  • Cognition / drug effects
  • Dietary Supplements
  • Energy Metabolism / drug effects
  • Gene Expression Regulation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Muscle, Skeletal / drug effects
  • NAD / metabolism*
  • NAD(P)H Dehydrogenase (Quinone) / metabolism*
  • Naphthoquinones / pharmacology*

Substances

  • Naphthoquinones
  • NAD
  • beta-lapachone
  • NAD(P)H Dehydrogenase (Quinone)
  • Nqo1 protein, mouse

Grant support

This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (Ministry of Education, Science and Technology; MEST) (to D.K., 20110028772, 2011k000273; and to J.M.K., 20110006229; and to S.-J.L., 20110004739), and the KRIBB (Korea Research Institute Bioscience and Biotechnology) Research Initiative Program of Korea (to C.H.L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.