Caloric Restriction and Rapamycin Differentially Alter Energy Metabolism in Yeast.
Rapamycin (RM), a drug that inhibits the mechanistic target of rapamycin (mTOR) pathway and responds to nutrient availability, seemingly mimics the effects of caloric restriction (CR) on healthy life span. However, the extent of the mechanistic overlap between RM and CR remains incompletely understood. Here, we compared the impact of CR and RM on cellular metabolic status. Both regimens maintained intracellular ATP through the chronological aging process and showed enhanced mitochondrial capacity. Comparative transcriptome analysis showed that CR had a stronger impact on global gene expression than RM. We observed a like impact on the metabolome and identified distinct metabolites affected by CR and RM. CR severely reduced the level of energy storage molecules including glycogen and lipid droplets, whereas RM did not. RM boosted the production of enzymes responsible for the breakdown of glycogen and lipid droplets. Collectively, these results provide insights into the distinct energy metabolism mechanisms induced by CR and RM, suggesting that these two anti-aging regimens might extend life span through distinctive pathways.
Institute of Animal Molecular Biotechnology, Korea University, Seoul, Republic of Korea.
Kyung-Mi
KM
Choi
Division of Biotechnology, College of Life Sciences & Biotechnology, Korea University, Seoul, Republic of Korea.
Seok-Jin
SJ
Hong
Departments of Biochemistry and Molecular Biology and Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota.
Jan M
JM
van Deursen
Department of Biotechnology, Graduate School, Korea University, Seoul, Republic of Korea.
Sooah
S
Kim
Department of Biotechnology, Graduate School, Korea University, Seoul, Republic of Korea.
Kyoung Heon
KH
Kim
Institute of Animal Molecular Biotechnology, Korea University, Seoul, Republic of Korea.|Division of Biotechnology, College of Life Sciences & Biotechnology, Korea University, Seoul, Republic of Korea.
Cheol-Koo
CK
Lee
D000375:Aging; D031204:Caloric Restriction; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D015151:Immunoblotting; D055442:Metabolome / Q000235:genetics; D046228:Microarray Analysis; D010101:Oxygen Consumption; D012331:RNA, Fungal / Q000032:analysis*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology*
D012331:RNA, Fungal; D020123:Sirolimus
Metabolomics; Transcriptomics