Beta-lapachone, a modulator of NAD metabolism, prevents health declines in aged mice.
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.
Department of Biological Sciences, KAIST (Korea Advanced Institute of Science and Technology), Daejeon, Korea.
Jeong-sook
JS
Lee
Ah Hyung
AH
Park
Sang-Hee
SH
Lee
Seoung-Hoon
SH
Lee
Jin-Hwan
JH
Kim
Suk-Jin
SJ
Yang
Young Il
YI
Yeom
Tae Hwan
TH
Kwak
Dongyeop
D
Lee
Seung-Jae
SJ
Lee
Chul-Ho
CH
Lee
Jin Man
JM
Kim
Daesoo
D
Kim
D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D031204:Caloric Restriction; D003071:Cognition / Q000187:drug effects; D019587:Dietary Supplements; D004734:Energy Metabolism / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D009243:NAD / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D009285:Naphthoquinones / Q000494:pharmacology*
D009285:Naphthoquinones; D009243:NAD; C014638:beta-lapachone; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse