86 6 ART for Antiaging
amino acids, cysteine and methionine, are downregulated, whereas degrada-
tion pathway genes for two kinds of nucleotide bases, purine and pyrimidine,
upregulated. From above results, we can predict that the biosynthesis of both
proteins and nucleic acids should be attenuated or even halted because of
food shortage and nutrition insufficiency in CR, which can be mimicked by
ART and H 2 O 2.
6.2.2.4 Downregulation of Genes for Protein Biosynthesis
and Upregulation of Genes for Protein Degradation
by CR and Mimetics
To further reveal the effect of CR and mimetics on protein biosynthesis and
degradation, we examined the expression levels of yeast ribosomal protein large
subunit genes (Rpl) and ribosomal protein small subunit genes (Rps) after treat-
ment by CR and mimetics. As the consequence, more Rpl/Rps and other related
genes are downregulated by CR and mimetics. During treatment, a dramatic
decreased protein concentration was noticed in all tested samples. These results
indicated that the biosynthesis of ribosomal proteins is inhibited, and ART or
H 2 O 2 can simulate CR in the modulation of ribosome genes and hence their
expression.
Accordingly, ribosome biogenesis genes that accelerate the ribosomal pro-
tein biosynthesis were found to be highly upregulated in all groups, implying
a feedback response of ribosomes from various stress conditions. Not surpris-
ingly, upregulation of ribosome biogenesis genes is more remarkable for the CR
group because its ribosome genes are extremely downregulated. At the same
time, we also analyzed the impact of different treatments on the controlled deg-
radation of proteins through ubiquitylation. Consequently, some ubiquitylation
genes (Ubi) are upregulated, but others downregulated. These results proved that
selective protein degradation is enhanced after treatments, by which amino acids
that are released from degraded proteins can be re-utilized. Furthermore, it was
also found that most of autophagy genes (Atg) are upregulated by each treatment
albeit a few of which are downregulated. It is clear that CR and mimetics can
partially augment autophagy in order to help yeast coping with environmental
stress (Fig. 6.1).
6.2.2.5 Mitohormesis: Modulation of Transporter Gene Expression
Profiles and Lipid Metabolic Patterns by CR and Mimetics
Genome-wide expression profiling was used in the present study to compare
the effects of CR and mimetics on ATP-binding cassette transporter gene
expression profiles and lipid metabolic patterns. The dynamic changes of SOD