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

Abstract

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 (parabss, eas, jus, ses B, tko 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 eas, ses B, and tko 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 ses B. 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.

Regulation of Aging and Longevity by Ion Channels and Transporters

“…Advanced age is also associated with increased neuronal activity in C. elegans , and pharmacological attenuation of excitability and its consequences using the Cl − channel agonist, ivermectin, or the L-type voltage-gated Ca 2+ channel (VGCC) blocker, nimodipine, extended worm lifespan [ 10 ] ( Figure 1 B). Roles for excitability in the regulation of neuronal viability and organismal lifespan are also observed in Drosophila [ 11 , 12 , 13 , 14 , 15 ] ( Figure 1 B). Deletion of the fly K + channel genes, ether a go-go ( eag ) and shaker ( Sh )—expected to augment neuronal excitability—led to severe loss of motor coordination, sleep deficits, and shorter lifespan [ 11 , 15 ].…”

Vps54 Regulates Lifespan and Locomotor Behavior in Adult Drosophila melanogaster

“…Bang sensitivity is a phenotype where affected flies are briefly paralyzed and seize upon receiving a short mechanical shock or “bang” ( Benzer, 1971 ; Ganetzky and Wu, 1982 ). Many bs mutations are in genes associated with mitochondrial function, shorted lifespan, and age-related neurodegenerative disease ( Reynolds, 2018 ). Each of these phenotypes have also been linked to the wobbler mouse ( Duchen and Strich, 1968 ; Santoro et al, 2004 ).…”

Vps54 regulates lifespan and locomotor behavior in adult Drosophila melanogaster

“…Bang sensitivity is a phenotype where affected flies are briefly paralyzed and seize upon receiving a short mechanical shock or "bang" (Benzer, 1971;Ganetzky and Wu, 1982). Many bs mutations are in genes associated with mitochondrial function, shorted lifespan, and age-related neurodegenerative disease (Reynolds, 2018).…”