Lifespan extension of Drosophila by reduction of polyamines

Brian M. Zid, Pankaj Kapahi, Seymour Benzer

Polyamines are small, ubiquitous polycations that are essential for normal growth. We discovered two defects in spermidine synthase, an enzyme in the polyamine biosynthetic pathway, that have increased lifespan in Drosophila. Ornithine decarboxylase (ODC), which is upregulated in many types of cancer, is the rate-limiting enzyme in the polyamine biosynthetic pathway. We have found that overexpression of gutfeeling, the Drosophila homolog of antizyme, an ODC inhibitor, also increases lifespan, and the long-lived mutants showed lower polyamine levels.

Polyamine levels were also found to be lower with dietary restriction and reduction of flux through the growth-promoting nutrient sensing TOR pathway. Tissues from dietary-restricted mice also showed reduced polyamines, indicating an evolutionarily conserved mechanism in which polyamines may be a link between dietary restriction and nutrient-sensing growth pathways.