83To disclose the involvement of H 2 O 2 in yeast lifespan extension, we treated
yeast cells by different concentrations of H 2 O 2. Consequently, H 2 O 2 in low con-
centrations (0.1, 0.5, and 20 μm) slightly extends lifespan, but H 2 O 2 in high con-
centrations (above 20 μm) renders rapid cell killing. These results demonstrated
that H 2 O 2 also promotes yeast longevity in a dose-dependent manner, and implied
that oxidative stress-induced antioxidative responses may be engaged in antiaging
effects.
6.2.2.2 Induction of Deferentially Expressed Genes
and Up/Downregulation of Specific Pathway
Genes by CR and Mimetics
To provide evidence supporting that ART or H 2 O 2 may exhibit a similarity with
CR in deferentially expressed yeast genes, we compared the CR and mimetics-
inducible transcripts from whole-transcriptome yeast expression profiling. In a
hierarchical clustering map based on all target values, those transcripts induced
by CR and mimetics exhibit significant difference from calorie nonrestriction.
According to cluster analysis, it is clear that transcripts from CR are partially com-
mon to those after treatment by mimetics, whereas transcripts from treatment by
mimetics are more similar than those from CR. While the inducible transcripts are
common between CR and H 2 O 2 as well as between CR and ART, other induci-
ble transcripts are unique for CR. Among those deferentially expressed genes, CR
induces more genes than ART. Additionally, the common regulated genes are less
for CR versus ART than for CR versus H 2 O 2.
According to the definition on yeast metabolic pathways in Kyoto
Encyclopedia of Genes and Genomes (KEGG), we analyzed the gene oncology
data and identified some regulated pathways among CR and mimetic treatments.
In all KEGG pathways with twofold up/downregulation, CR down/upregulates
more pathways, whereas ART down/upregulates less ones. For all treatments, the
ribosome pathway and MAPK signaling pathway are downregulated, whereas
meiosis pathway upregulated (Wang et al. 2014 ).
6.2.2.3 Induction of Metabolic Alterations from Biosynthesis
to Degradation of Metabolites
Although the microarray data of inducible pathway genes are available for differ-
ent treatments, some have not been depicted in gene ontology diagrams because of
insignificance (less than twofold up/downregulation) as comparison with calorie
nonrestriction. To address that ART and H 2 O 2 mimic CR in metabolic modulation-
related gene expression, we parallelly quantified the metabolic pathway transcripts
responsible for the metabolisms of glucose, fatty acids, amino acids, and nucleo-
tides in CR and mimetic groups (Table 6.1).
6.2 ART Extends Yeast Lifespan via NO Signaling