Shortened Lifespan and Other Age-Related Defects in Bang Sensitive Mutants of Drosophila melanogaster

摘要

Mitochondrial diseases are complex disorders that exhibit their primary effects in energetically active tissues. Damage generated by mitochondria is also thought to be a key component of aging and age-related disease. An important model for mitochondrial dysfunction is the bang sensitive (bs) mutants in Drosophila melanogaster. Although these mutants all show a striking seizure phenotype, several bs mutants have gene products that are involved with mitochondrial function, while others affect excitability another way. All of the bs mutants (, , , , are examined here) paralyze and seize upon challenge with a sensory stimulus, most notably mechanical stimulation. These and other excitability mutants have been linked to neurodegeneration with age. In addition to these phenotypes, we have found age-related defects for several of the bs strains. The mutants , , and display shortened lifespan, an increased mean recovery time from seizure with age, and decreased climbing ability over lifespan as compared to isogenic CS or w¹¹¹⁸ lines. Other mutants show a subset of these defects. The age-related phenotypes can be rescued by feeding melatonin, an antioxidant, in all the mutants except . The age-related defects do not appear to be correlated with the seizure phenotype. Inducing seizures on a daily basis did not exacerbate the phenotypes and treatment with antiepileptic drugs did not increase lifespan. The results suggest that the excitability phenotypes and the age-related phenotypes may be somewhat independent and that these phenotypes mutants may arise from impacts on different pathways.