1. Cell Metab. 2007 Oct;6(4):280-93.

Glucose restriction extends Caenorhabditis elegans life span by inducing
mitochondrial respiration and increasing oxidative stress.

Schulz TJ(1), Zarse K, Voigt A, Urban N, Birringer M, Ristow M.

Author information: 
(1)Department of Human Nutrition, Institute of Nutrition, University of Jena,
D-07743 Jena, Germany.

Increasing cellular glucose uptake is a fundamental concept in treatment of type 
2 diabetes, whereas nutritive calorie restriction increases life expectancy. We
show here that increased glucose availability decreases Caenorhabditis elegans
life span, while impaired glucose metabolism extends life expectancy by inducing 
mitochondrial respiration. The histone deacetylase Sir2.1 is found here to be
dispensable for this phenotype, whereas disruption of aak-2, a homolog of
AMP-dependent kinase (AMPK), abolishes extension of life span due to impaired
glycolysis. Reduced glucose availability promotes formation of reactive oxygen
species (ROS), induces catalase activity, and increases oxidative stress
resistance and survival rates, altogether providing direct evidence for a
hitherto hypothetical concept named mitochondrial hormesis or "mitohormesis."
Accordingly, treatment of nematodes with different antioxidants and vitamins
prevents extension of life span. In summary, these data indicate that glucose
restriction promotes mitochondrial metabolism, causing increased ROS formation
and cumulating in hormetic extension of life span, questioning current treatments
of type 2 diabetes as well as the widespread use of antioxidant supplements.

DOI: 10.1016/j.cmet.2007.08.011 
PMID: 17908557  [Indexed for MEDLINE]