109Abstract The exact mechanisms behind aging-related diseases remain unknown.
Oxidative/nitrosative stress-mediated posttranslational modifications leading to
protein misfolding and structural/functional abnormality have been supposed to be
the plausible pathogenic initiators of neurodegenerative diseases. Obesity might
be an outcome of the activation of iNOS and inactivation of eNOS, leading to
mitochondrial loss and adipose whitening without adipose burning. Inflammation-
driven mitochondrial dysfunction might be the intrinsic effector of Warburg effects
showing potent ROS burst, which should enhance mutagenesis and tumorigenesis/
carcinogenesis.
Keywords Aging-related disease · Cancer · Obesity · Warburg effect
As an endogenous signaling molecule, NO is critical for metabolic homeostasis
and cell cycle among multifaceted functions. NO not only vasodilates blood ves-
sels, but also delays aging and extends lifespan. Intriguingly, NO is employed
to assist the immune system to kill invaders. In the presence of O 2 −, NO is con-
verted to the potent oxidant ONOO−, which would cause a series of adverse con-
sequences if sustained, mainly including DNA damage and gene mutation as well
as protein misfolding and dysfunction.
Whether NO is a “friend” or a “foe” depends on its origination and relative lev-
els, among which the physiological NO generates in a low level from eNOS or
nNOS, whereas the pathological NO bursts in a high level from iNOS (Ignarro
2010 ). Therefore, low-level NO usually exerts a beneficial effect and physiologi-
cal function, while high-level NO is beneficial to attacking pathogens but harmful
by causing tissue damage. During aging, eNOS and nNOS activities gradually
decline, and mtNOS activity maintains for only 45–75 % (Boveris et al. 2010 ),
suggesting NO in older persons is insufficient to maintain the normal physiologi-
cal function.
Environmental stresses originated from ROS and RNS are major pathogenic
side effectors that potentially initiate physiological disorders. By a dependent
and interactive way, ROS and RNS not only cause DNA damage, but also modify
Chapter 7
Prospective
© The Author(s) 2015
Q.-P. Zeng, Artemisinin and Nitric Oxide, SpringerBriefs in Molecular Science,
DOI 10.1007/978-3-662-47688-8_7