A reduction in age-enhanced gluconeogenesis extends lifespan.
The regulation of energy metabolism, such as calorie restriction (CR), is a major determinant of cellular longevity. Although augmented gluconeogenesis is known to occur in aged yeast cells, the role of enhanced gluconeogenesis in aged cells remains undefined. Here, we show that age-enhanced gluconeogenesis is suppressed by the deletion of the tdh2 gene, which encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein that is involved in both glycolysis and gluconeogenesis in yeast cells. The deletion of TDH2 restores the chronological lifespan of cells with deletions of both the HST3 and HST4 genes, which encode yeast sirtuins, and represses the activation of gluconeogenesis. Furthermore, the tdh2 gene deletion can extend the replicative lifespan in a CR pathway-dependent manner. These findings demonstrate that the repression of enhanced gluconeogenesis effectively extends the cellular lifespan.
National Food Research Institute, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
Mayumi
M
Hachinohe
Midori
M
Yamane
Daiki
D
Akazawa
Kazuhiro
K
Ohsawa
Mayumi
M
Ohno
Yuzu
Y
Terashita
Hiroshi
H
Masumoto
D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics; D017353:Gene Deletion; D005943:Gluconeogenesis / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000172:deficiency / Q000235:genetics; D006655:Histone Deacetylases / Q000172:deficiency / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D013997:Time Factors
D029701:Saccharomyces cerevisiae Proteins; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); C465225:TDH2 protein, S cerevisiae; C512517:Hst3 protein, S cerevisiae; C512518:Hst4 protein, S cerevisiae; D006655:Histone Deacetylases; D005947:Glucose