103downregulation of protein turnover-relevant ubiquitylation pathway genes, includ-
ing DNA repair-responsible tumor suppressors such as BRCA1. Surprisingly,
exogenous H 2 O 2 can also correlate the repression of oxidative stress with the
mitigation of telomere attrition, suggesting an involvement of antioxidation in the
attenuation of DNA damage and DNA repair. Indeed, telomeres are kept almost
intact without the upregulation of Tert gene and TERT enzyme, implying tel-
omere maintenance rather than telomere elongation. As a functional NO mimetic,
ART may exert its role directly through binding to COX leading to mitochon-
drial uncoupling, or indirectly via first binding to NOS for NO production and
then binding to COX leading to mitochondrial uncoupling. We also established a
solid link between NO signaling and mitochondrial biogenesis by monitoring the
increased numbers of mitochondria followed by the elevated levels of NO and ATP
upon exposure to CR mimetics. In conclusion, CR-triggered NO promotes mito-
chondrial biogenesis, leading to the activation of whole antioxidative networks and
alleviation of telomere erosion, thereby maintaining the stability and integrity of
chromosomes, which are the hallmarks of longevity.
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6.3 ART as a NO Mimetic Compromises Mouse Telomere Shortening