Improved functional abilities of the life-extended Drosophila mutant Methuselah are reversed at old age to below control levels

Abstract

Methuselah (mth) is a chromosome 3 Drosophila mutant with an increased lifespan. A large number of studies have investigated the genetic, molecular, and biochemical mechanisms of the mth gene. Much less is known about the effects of mth on preservation of sensorimotor abilities throughout Drosophila's lifespan, particularly in late life. The current study investigated functional senescence in mth and its parental-control line (w1118) in two experiments that measured age-dependent changes in flight functions and locomotor activity. In experiment 1, a total of 158 flies (81 mth and 77 controls) with an age range from 10 to 70 days were individually tethered under an infrared laser-sensor system that allowed monitoring of flight duration during phototaxic flight. We found that mth has a statistically significant advantage in maintaining continuous flight over control flies at age 10 days, but not during middle and late life. At age 70 days, the trend reversed and parental control flies had a small but significant advantage, suggesting an interaction between age and genotype in the ability to sustain flight. In experiment 2, a total of 173 different flies (97 mth and 76 controls) with an age range from 50 to 76 days were individually placed in a large well-lit arena (60×45 cm) and their locomotor activity quantified as the distance walked in a 1-min period. Results showed that mth flies had lower levels of locomotor activity relative to controls at ages 50 and 60 days. These levels converged for the two genotypes at the oldest ages tested. Findings show markedly different patterns of functional decline for the mth line relative to those previously reported for other life-extended genotypes, suggesting that different life-extending genes have dissimilar effects on preservation of sensory and motor abilities throughout an organism's lifespan.

Efficacy of methuselah gene mutation toward tolerance of dichlorvos exposure in Drosophila melanogaster

“…However, this rescue in locomotor insufficiency was not evident in DDVP-exposed 30-day-old mth 1 flies compared to their age-matched w 1118 flies. Our observation finds support from a previous study wherein mth 1 flies showed improved functional abilities up to middle ( $ day 20) age and their reversal at late age as against w 1118 flies [53]. As a proof of principle, we genetically modulated the expression of mth (over-expression and knockdown) in flies to examine life span, locomotor performance, and cellular redox state after their prolonged exposure to DDVP.…”

“…Therefore, we examined the life span of mth 1 flies after their prolonged exposure to DDVP and observed a significant improvement in the life span of these flies compared with similarly exposed w 1118 flies ( $ 12 and 35% reduction in life span of similarly exposed w 1118 and mth 1 flies). In addition to improved life span, earlier studies have shown decreased efficiency of mth mutation toward cellular as well as organismal benefits in the long run [17,53]. Increased life span is causally linked with enhanced antioxidant defense vis-à-vis reduced oxidative damage.…”

Enhanced tethered-flight duration and locomotor activity by overexpression of the human gene SOD1 in Drosophila motorneurons

“…These include simple motor functions such as flight duration at early and middle life, and locomotor activity in late life. A comparison of the current results to our earlier studies ( Petrosyan et al , 2007 , 2013 , 2014 ) suggests that different life-extending genes may yield different patterns of functional stability at various stages of life. Whether these different genetic strategies may be used in concert to broadly promote robust motor, sensory, memory, and other functions in late life, merits further investigation.…”

“…Tethered flies were moved to the experimental chamber, fed with a small piece of filter paper dipped in sucrose-water, and allowed to rest and become acclimated to the experimental environment for an additional 30–60 min prior to data collection. Prior work has shown that this is a sufficient period of time for full recovery from anesthesia ( Lehmann and Dickinson, 1997 ; Petrosyan et al , 2007 , 2013 , 2014 ).…”

Effect of Wolbachia Infection on Aging and Longevity-Associated Genes in Drosophila

“…The methuselah (mth) gene, encoding G-protein-coupled receptor, is known to be associated with longevity and stress resistance in Drosophila (Petrosyan et al 2014). Mutations decreasing the activity of this gene are known to extend the life span in flies (Lin et al 1998).…”