PMID- 24126084 OWN - NLM STAT- MEDLINE DCOM- 20140730 LR - 20131122 IS - 1873-6815 (Electronic) IS - 0531-5565 (Linking) VI - 48 IP - 12 DP - 2013 Dec TI - Characterization of global gene expression during assurance of lifespan extension by caloric restriction in budding yeast. PG - 1455-68 LID - S0531-5565(13)00302-1 [pii] LID - 10.1016/j.exger.2013.10.001 [doi] AB - Caloric restriction (CR) is the best-studied intervention known to delay aging and extend lifespan in evolutionarily distant organisms ranging from yeast to mammals in the laboratory. Although the effect of CR on lifespan extension has been investigated for nearly 80years, the molecular mechanisms of CR are still elusive. Consequently, it is important to understand the fundamental mechanisms of when and how lifespan is affected by CR. In this study, we first identified the time-windows during which CR assured cellular longevity by switching cells from culture media containing 2% or 0.5% glucose to water, which allows us to observe CR and non-calorically-restricted cells under the same conditions. We also constructed time-dependent gene expression profiles and selected 646 genes that showed significant changes and correlations with the lifespan-extending effect of CR. The positively correlated genes participated in transcriptional regulation, ribosomal RNA processing and nuclear genome stability, while the negatively correlated genes were involved in the regulation of several metabolic pathways, endoplasmic reticulum function, stress response and cell cycle progression. Furthermore, we discovered major upstream regulators of those significantly changed genes, including AZF1 (YOR113W), HSF1 (YGL073W) and XBP1 (YIL101C). Deletions of two genes, AZF1 and XBP1 (HSF1 is essential and was thus not tested), were confirmed to lessen the lifespan extension mediated by CR. The absence of these genes in the tor1Delta and ras2Delta backgrounds did show non-overlapping effects with regard to CLS, suggesting differences between the CR mechanism for Tor and Ras signaling. CI - (c) 2013. FAU - Choi, Kyung-Mi AU - Choi KM AD - Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea. FAU - Kwon, Young-Yon AU - Kwon YY FAU - Lee, Cheol-Koo AU - Lee CK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131011 PL - England TA - Exp Gerontol JT - Experimental gerontology JID - 0047061 RN - 0 (AZF1 protein, S cerevisiae) RN - 0 (DNA-Binding Proteins) RN - 0 (HSF1 protein, S cerevisiae) RN - 0 (Heat-Shock Proteins) RN - 0 (RNA, Fungal) RN - 0 (RNA, Ribosomal) RN - 0 (Repressor Proteins) RN - 0 (Saccharomyces cerevisiae Proteins) RN - 0 (Transcription Factors) RN - 0 (XBP1 protein, S cerevisiae) RN - IY9XDZ35W2 (Glucose) SB - IM MH - *Caloric Restriction MH - DNA-Binding Proteins/genetics/metabolism MH - Gene Deletion MH - *Gene Expression Profiling/methods MH - *Gene Expression Regulation, Fungal MH - Glucose/metabolism MH - Heat-Shock Proteins/genetics/metabolism MH - Longevity/*genetics MH - Mutation MH - RNA, Fungal/metabolism MH - RNA, Ribosomal/metabolism MH - Repressor Proteins/genetics/metabolism MH - Ribosomes/genetics/metabolism MH - Saccharomyces cerevisiae/*genetics/growth & development MH - Saccharomyces cerevisiae Proteins/*genetics/metabolism MH - Time Factors MH - Transcription Factors/genetics/metabolism MH - Transcription, Genetic OTO - NOTNLM OT - Budding yeast OT - CR OT - Caloric restriction OT - LGS OT - Longevity assurance OT - Transcription factor OT - Transcriptome OT - caloric restriction OT - longevity-related gene set EDAT- 2013/10/16 06:00 MHDA- 2014/07/31 06:00 CRDT- 2013/10/16 06:00 PHST- 2013/02/25 00:00 [received] PHST- 2013/09/28 00:00 [revised] PHST- 2013/10/03 00:00 [accepted] PHST- 2013/10/16 06:00 [entrez] PHST- 2013/10/16 06:00 [pubmed] PHST- 2014/07/31 06:00 [medline] AID - S0531-5565(13)00302-1 [pii] AID - 10.1016/j.exger.2013.10.001 [doi] PST - ppublish SO - Exp Gerontol. 2013 Dec;48(12):1455-68. doi: 10.1016/j.exger.2013.10.001. Epub 2013 Oct 11.