Tor-Sch9 deficiency activates catabolism of the ketone body-like acetic acid to promote trehalose accumulation and longevity

Aging Cell. 2014 Jun;13(3):457-67. doi: 10.1111/acel.12202. Epub 2014 Mar 20.


In mammals, extended periods of fasting leads to the accumulation of blood ketone bodies including acetoacetate. Here we show that similar to the conversion of leucine to acetoacetate in fasting mammals, starvation conditions induced ketone body-like acetic acid generation from leucine in S. cerevisiae. Whereas wild-type and ras2Δ cells accumulated acetic acid, long-lived tor1Δ and sch9Δ mutants rapidly depleted it through a mitochondrial acetate CoA transferase-dependent mechanism, which was essential for lifespan extension. The sch9Δ-dependent utilization of acetic acid also required coenzyme Q biosynthetic genes and promoted the accumulation of intracellular trehalose. These results indicate that Tor-Sch9 deficiency extends longevity by switching cells to an alternative metabolic mode, in which acetic acid can be utilized for the storage of stress resistance carbon sources. These effects are reminiscent of those described for ketone bodies in fasting mammals and raise the possibility that the lifespan extension caused by Tor-S6K inhibition may also involve analogous metabolic changes in higher eukaryotes.

Keywords: Sch9; acetic acid; aging; chronological lifespan; leucine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetic Acid / metabolism*
  • Humans
  • Longevity / physiology*
  • Phosphatidylinositol 3-Kinases / deficiency*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinases / deficiency*
  • Protein Kinases / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Trehalose / metabolism*


  • Saccharomyces cerevisiae Proteins
  • Trehalose
  • Protein Kinases
  • SCH9 protein kinase
  • TOR1 protein, S cerevisiae
  • Acetic Acid