Modulating Longevity in Drosophila by Over‐ and Underexpression of Glutamate‐Cysteine Ligase

• DOI: 10.1196/annals.1404.000
• Publication Date: 2007-12-05T02:57:04Z
• Authors: JAMES M. LUCHAK; LEENA PRABHUDESAI; RAJINDAR S. SOHAL; SVETLANA N. RADYUK; WILLIAM C. ORR
• Keywords: GCLM

A notable extension of life span (up to 50%) was achieved in Drosophila melanogaster when the catalytic subunit glutamate-cysteine ligase (GCLc) overexpressed neuronal tissue, while a moderate increase 24%) observed modulatory GCL (GCLm) globally. We sought identify specific tissue domains that are particularly sensitive beneficial effects GCLc overexpression. Overexpression using mushroom body driver (OK107-GAL4) had small but significant effect on longevity (approximately 12%) overexpression serotonergic (MZ360-GAL4) neurons or dopaminergic and (Ddc-GAL4) small, nonsignificant longevity. (12-13%) also C23-GAL4 transverse muscle driver. Finally, low-level global (armadillo) shown significantly (15%). series mutant knockdown studies were carried out. Reduction GCLm by > 95% no discernable resistance oxidative stress. In contrast, 30-70% an RNAi-hairpin strategy effect, resulting greater sensitivity H(2)O(2) reduced survivorship under normal conditions varying from 50% reduction median lethality. null allele identified be recessive lethal. Overall, this study demonstrates dependent dosage there tissues (mushroom bodies, motor neurons, cells) benefits