94 6 ART for Antiaging
CR exerts a role in yeast lifespan extension experiencing two stages: the one
is enhanced antioxidation to allow the mitigation of ROS generation in the ME
phase via respiratory burst; and another is attenuated metabolism to allow the
adaption to food shortage in the PME phase via respiratory decay. CR-extended
lifespan can be partially mimicked by ART and H 2 O 2 via the induction of antioxi-
dant responses and alteration of metabolic responses, which are mirrored by global
transcriptome profiling and other sensitive detection procedures.
6.2.4 Conclusions
Although CR-prolonged lifespan is suggested to associate with mitochondrial
biogenesis leading to enhanced respiratory activity, it is apparently controversial
for that accelerated energy consumption occurs regardless of insufficient nutrient
intake. In reconciling the contradiction of less food supply versus much metabo-
lite dispense, we surprisingly noticed a specific mode of CR-based “dual-phase
responses” that encompass the phases of ME and PME, which can be distin-
guished by the expression modes and activity dynamics of mitochondrial sig-
natures. The PME phase is characterized by the downregulation of biosynthesis
pathway genes and corresponding upregulation of degradation pathway genes.
While protein biosynthesis-gated ribosome genes are downregulated, protein
degradation-tuned ubiquitylation genes upregulated. CR-exerted aging-delaying
effects can be mimicked by ART, suggesting that ART-heme conjugation func-
tionally resembles NO-heme interaction and therefore establishing a correlation
of ART-heme conjugates with increased COX activity. Like CR and ART elic-
iting antioxidative responses and initiating metabolic modulations, exogenous
H 2 O 2 also induces antioxidant genes and alters respiratory rhythms, thereby
extending yeast lifespan. In conclusion, the available data would provide a per-
fect explanation to the paradoxical outcome of yeast mitochondrial respiratory
activity during CR.
6.3 ART as a NO Mimetic Compromises Mouse Telomere
Shortening
6.3.1 Purposes and Significance
CR is known to extend lifespan among distinct organisms with the putative mech-
anism underlying NO-driven enhanced mitochondrial biogenesis, but whether NO
also protects the chromosomal telomeres from erosion remains elusive and incon-
clusive. Telomeres protect chromosomal ends from degradation, and DNA repair
activities, therefore, are essential for chromosome stability (Chan and Blackburn
2002 ). The telomere length is considered a “molecular clock” of progressive