Data from: Drosophila clock is required in brain pacemaker neurons to prevent premature locomotor aging independently of its circadian function

Circadian clocks control many self-sustained rhythms in physiology and
behavior with approximately 24-hour periodicity. In many organisms,
oxidative stress and aging negatively impact the circadian system and
sleep. Conversely, loss of the clock decreases resistance to oxidative
stress, and may reduce lifespan and speed up brain aging and
neurodegeneration. Here we examined the effects of clock disruptions on
locomotor aging and longevity in Drosophila. We found that lifespan was
similarly reduced in three arrhythmic mutants (ClkAR, cyc0 and tim0) and
in wild-type flies under constant light, which stops the clock. In
contrast, ClkAR mutants showed significantly faster age-related locomotor
deficits (as monitored by startle-induced climbing) than cyc0 and tim0, or
than control flies under constant light. Reactive oxygen species
accumulated more with age in ClkAR mutant brains, but this did not appear
to contribute to the accelerated locomotor decline of the mutant. Clk, but
not Cyc, inactivation by RNA interference in the pigment-dispersing factor
(PDF)-expressing central pacemaker neurons led to similar loss of climbing
performance as ClkAR. Conversely, restoring Clk function in these cells
was sufficient to rescue the ClkAR locomotor phenotype, independently of
behavioral rhythmicity. Accelerated locomotor decline of the ClkAR mutant
required expression of the PDF receptor and correlated to an apparent loss
of dopaminergic neurons in the posterior protocerebral lateral 1 (PPL1)
clusters. This neuronal loss was rescued when the ClkAR mutation was
placed in an apoptosis-deficient background. Impairing dopamine synthesis
in a single pair of PPL1 neurons that innervate the mushroom bodies
accelerated locomotor decline in otherwise wild-type flies. Our results
therefore reveal a novel circadian-independent requirement for Clk in
brain circadian neurons to maintain a subset of dopaminergic cells and
avoid premature locomotor aging in Drosophila.