113in the defective transfer of proteins to ubiquitin. In the proteosome, mutations of
the E3-ligase parkin explain the appearance of juvenile Parkinson’s disease by
the less degradation of NOS and aggravation of excess NO-mediated mitochondrial
damage and complex I abrogation (Boveris et al. 2010 ).
Due to reaction with the excessive O 2 − leading to generation of ONOO−, the
scarcely available NO should exist during aging. Indeed, senescent endothelial
cells display higher mTORC1 activity, increased O 2 − production and decreased
bioactive NO levels than young endothelial cells. This is contributed by the so-
called “uncoupling” of NOS that does not produce NO but O 2 −. Silencing
mTORC1 in senescent cells reduces O 2 − generation and enhances NO production,
whereas the overexpression of a constitutively active mTORC1 mutant in young
endothelial cells mimics endothelial dysfunction of senescent cells through NOS
uncoupling and induces premature cellular senescence. RAP and resveratrol, by
inhibiting mTORC1 signaling, result in the decrease of O 2 − levels, but increase
of NO levels in the senescent cells as well as in the aortas of old rats (Rajapakse
et al. 2011 ). Likewise, short-term CR initiated in old age reverses age-associated
vascular endothelial dysfunction by restoring NO bioavailability, reducing NADH
oxidase-mediated O 2 − production, stimulating antioxidant enzyme activity, and
upregulating SIRT1 (Rippe et al. 2010 ).
7.2 Low-Grade Inflammation as an Essential Consequence
of Obesity?
In regard to obesity, there are many unsolved problems. Is obesity a disease? Is the
fat deposited in the subcutaneous adipose tissue (SAT) benign, but the fat depos-
ited in the visceral adipose tissue (VAT) malignant? Does the brown adipose tissue
(BAT) or the white adipose tissue (WAT) distinguish the healthy or unhealthy obe-
sity? Does chronic inflammation induce obesity and insulin resistance? Does the
antihypoxic intervention reduce body weight and improve insulin sensitivity?
There has a definition of obese/lean not strictly based on the body mass index
(BMI), but has no specific standards to distinguish the composition of an indi-
vidual that is composed of the adipose and muscle tissues. However, some above
mentioned terms such as SAT or VAT as well as BAT or WAT have been employed
to describe the features of adiposity. SAT localizes under the skin, arms, breasts,
buttocks, hips, and thighs, while VAT distributes around or within the liver, heart,
muscles, and pancreas. BAT rather than WAT has an extraordinary number of
mitochondria and numerous capillaries, allowing it to look dark and gland-like.
BAT is more active than WAT in lipid degradation and energy expenditure.
Although the American Medical Association (AMA) declare obesity to be a
disease, Katz ( 2014 ) recently argued that obesity is not a disease, but a risk factor
of other chronic diseases. This is because not only can chronic diseases develop in
the absence of obesity, but not every obese person develops any such conditions.
A BMI-based thin person might have an increased fat depot in VAT. In similar,
7.1 Nitrosylation/Nitration in the Active Center of Proteins ...