Extension of Health Span and Life Span in Drosophila by S107 Requires the calstabin Homologue FK506-BP2.
The accumulation of oxidative damage is strongly linked to age-dependent declines in cell function, but the contribution of oxidative damage to morbidity is still debated. Many organisms seem to tolerate oxidative damage, and the extension of health span and life span by augmenting antioxidant activity has been inconsistent. Here we use the Drosophila model system to investigate the relationship among oxidative stress, health span, and life span. The oxidation-dependent dissociation of the Calstabin protein from the ryanodine receptor has been shown to result in reduced muscle function in mammals. The S107 molecule is able to reestablish this binding resulting in improved muscle function. We find that S107 is able to restore motor function in aging Drosophila to young levels, and this effect of S107 is absent in calstabin (FK506-BP2) mutants. Interestingly, FK506-BP2 mutant flies have reduced sensitivity to the effects of age and oxidative stress on motor function between 7 and 35 days of age. Muscle expression of FK506-BP2 in FK506-BP2 mutants completely restores the sensitivity of motor function to both age and oxidative stress, supporting the idea that the age-dependent decline in motor function in Drosophila requires FK506-BP2 function within the muscle. Although FK506-BP2 mutant flies are found to have less sensitivity to oxidative stress, FK506-BP2 mutants do not live longer than wild type. These results demonstrate that the deleterious effects of oxidation on motor function early in life are the result of a singular event that does not compromise survival.
From the Department of Integrative and Cellular Physiology, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas 78229.
Tabita
T
Kreko-Pierce
From the Department of Integrative and Cellular Physiology, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas 78229.
Jorge
J
Azpurua
From the Department of Integrative and Cellular Physiology, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas 78229.
Rebekah E
RE
Mahoney
From the Department of Integrative and Cellular Physiology, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas 78229 eatonb@uthscsa.edu.
Benjamin A
BA
Eaton
D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D008136:Longevity / Q000187:drug effects* / Q000235:genetics; D009132:Muscles / Q000378:metabolism*; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013841:Thiazepines / Q000494:pharmacology*
D029721:Drosophila Proteins; C540746:S-107 compound; D013841:Thiazepines; D022021:Tacrolimus Binding Proteins
Drosophila; aging; muscle physiology; oxidative stress; ryanodine receptor