Hexosamine metabolites enhance protein quality control and longevity

Adam Antebi
Adam Antebi
Max Planck Institute for Biology of Ageing, Germany
15:50~16:40, November 21st, 2013


Ageing is a major risk factor for numerous diseases, including neurodegeneration, which can result from a progressive decline in cellular protein homeostasis. We have recently discovered that activation of the hexosamine pathway (HP) through gain-of-function (gof) mutations in glucosamine-fructose 6-phosphate aminotransferase (GFAT-1), the HP key enzyme, lead to improved protein homeostasis and extended life span in the nematode Caenorhabditiselegans. GFAT-1 gof mutations elevate production of UDP-N-acetylglucosamine (UDP-GlcNAc), and feeding this metabolite to wildtype worms alleviates pathology in distinct neurotoxicity models and promotes longevity. Clearance of protein aggregates and longevity depend on ER-associated degradation, proteasomal activity, and autophagy. This discovery may open up new possibilities towards treatments of age-related and proteotoxic diseases


Research Interests :

  • Hormonal regulation of longevity
  • Developmental timing
  • Protein homeostasis and neurodegeneration
  • Dietary restriction mediated longevity


Awards and Honors:

  • Glenn/AFAR Breakthrough in Gerontology Award (2005-2007)
  • Ellison Medical Foundation Senior Scholar in Aging Award (2007-2012)
  • Runnstrom Lecture Award (2009)