9burst, ROS activate antioxidative responses, and antioxidation alleviates oxidative
stress. In similar, mitochondrial uncouplers that target the respiratory chain, such as
DNP, also provoke ROS generation, induce antioxidative responses, and scavenge
ROS, eventually mimic CR’s healthy effects.
1.3 The Purpose of Writing the Book
Most recently, a youth-keeping protein, growth differentiation factor 11 (GDF-11),
has been identified in the blood of young mice, but whether its antiaging mecha-
nism involves NO signaling is totally unclear. It is known that the “young blood” can
activate stem cells and rejuvenate organs and cells in old mice, whereas the “aging
blood” can inhibit regenerative capacity in young mice (Hall 2014 ). To my assump-
tion, GDF-11 might maintain a relative high level in young mice, whereas it might be
lower in aging mice. Alternatively, it can be that youngers would keep a natural form
of GDF-11, whereas olders would possess a partially denatured form of GDF-11, per-
haps due to the ONOO−-mediated nitration in aging mice. Surprisingly, GDF-11 as
an authentic youth factor (Loffredo et al. 2013 ; Sinha et al. 2014 ) has been currently
argued by indicating that myostatin was actually misidentified as GDF-11 (Egerman
et al. 2015 ). However, no response has been given from authors until now.
From a detailed introduction and a deep discussion in this seven-chapter book,
I have tried to preliminarily reveal the secrets of longevity and aging-related
pathogenesis, and also attempted to validate the threshold mechanism underlying
NO-mediated disease and health potentials (Fig. 1.2).
Fig. 1.2 A schematic outline of the threshold theory of NO-mediated disease and health effects
showing the dichotomy between physiological low-level NO and pathological high-level NO. CR
calorie restriction; eNOS endothelial nitric oxide synthase; iNOS inducible nitric oxide synthase;
LPS lipopolysaccharide; nNOS neuronal nitric oxide synthase; NO nitric oxide; RNS reactive
nitrogen species; ROS reactive oxygen species
1.2 A Uniform NO Threshold Theory in Disease and Health