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

Aging Cell

Jia Hu³  Min Wei³  Hamed Mirzaei³  Federica Madia³  Mirisola Mario³  Camille Amparo¹  Shawna Chagoury¹  Brian Kennedy² 

[1] Department of Biological Sciences, School of Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA;Buck Institute for Research on Aging, Novato, CA, USA;Longevity Institute, Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA

关键词: acetic acid;    aging;    chronological lifespan;    leucine;    Sch9;   

DOI  :  10.1111/acel.12202

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

CC BY   
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.