Artemisinin and Nitric Oxide Mechanisms and Implications in Disease and Health

(Darren Dugan) #1
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Abstract ART can mimic CR to extend yeast lifespan, during which both ART
and CR-triggered NO can activate antioxidative responses and convert the meta-
bolic pattern from biosynthesis to degradation. ART also mimics CR to com-
promise mouse telomere shortening by upregulating antioxidative enzymes for
effective ROS scavenging, which is followed by the alleviation of DNA damage
and downregulation of tumor suppressors. This is the first time for having found
ART exerting an antiaging role.


Keywords Antioxidation · ART · CR · Lifespan · Telomere


6.1 An Overview on Aging and Antiaging


CR, limited food intake without malnutrition, is an extensively reproducible inter-
vention in lifespan extension among organisms ranging from yeast to mammals
(Koubova and Guarente 2003 ; Spindler 2010 ). Owing to evolutionary conservation,
CR-enhanced longevity has been frequently described in yeast (Jiang et al. 2000 ),
nematodes (Walker et al. 2005 ), fruit flies (Rogina and Helfand 2004 ), and mam-
mals (Youngman et al. 1992 ). In yeast, the chronological lifespan (CLS) and the rep-
licative lifespan (RLS) are extended by glucose reduction from 2 to 0.5 %. While
CLS is more relevant to postmitotic cell aging, RLS is closely related to replicative
aging seen in stem cells (Skinner and Lin 2010 ). In primates, when daily diets are
restricted to 40 % as ad libitum (AL) feeding, some commonly occurred age-related
diseases, including cancer, diabetes, atherosclerosis, neurodegenerative disorders,
and respiratory failures, can be mostly delayed (Kenyon 2005 ; Colman et al. 2009 ;
Mattison et al. 2012 ). CR in humans also greatly reduces the subjected risks of can-
cer, diabetes, and cardiovascular diseases (Fontana and Klein 2007 ).
CR is believed to exert a longevity-promoting effect through enhanced mitochon-
drial biogenesis (López-Lluch et al. 2006 ; Civitarese et al. 2007 ), which is initi-
ated by NO generated from eNOS (Nisoli et al. 2003 , 2005 ) and/or nNOS/mtNOS
(Giulivi et al. 1998 ; Finocchietto et al. 2008 ). In mammals, CR is known to induce


Chapter 6


ART for Antiaging


© The Author(s) 2015
Q.-P. Zeng, Artemisinin and Nitric Oxide, SpringerBriefs in Molecular Science,
DOI 10.1007/978-3-662-47688-8_6

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