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

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 thatmeasured 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.
The mth and control flies were graciously provided by the laboratory of the late Prof. Seymour Benzer. We thank Rosana Magalhaes, Eugenia Fernandes, and Jorge Alves for helpful discussions. This work was supported by funding from the University of California, Irvine, and from the University of Minho, Portugal.