Fig. 1. Loss of the repressive arm of the transcriptional circadian clock extends male lifespan.

a Schematic of core molecular clock components and circadian transcriptional feedback loop. Relative to controls (gray), mutant males lacking Cyc function (yellow, b) or expressing dominant-negative clock (daGS > UAS-DN-Clock flies fed RU486, orange, c) show reduced lifespan (p < 0.0001 for each circadian mutant vs. control). In contrast, tim⁰¹ mutants (blue, d) and per⁰¹ mutants (green, e) live longer than controls (gray), even on diets with different concentrations of yeast extract (f, g), except for the highest yeast diet (p < 0.001 for each circadian mutant vs. control on each diet). h per⁰¹ mutants with daGS > UAS-DN-S6K fed either RU486 (dashed lines) or vehicle (solid lines) exhibited similar lifespan extension relative to controls containing daGS > UAS-DN-S6K. i per⁰¹ mutant males containing either the dilp2-GAL4 driver alone (solid lines) or dilp2-GAL4 > UAS-reaper and ablated for insulin-producing cells (dashed lines) exhibit similar lifespan extension relative to controls. See Supplementary Table 1 for n and p values for lifespan experiments, particularly multicurve comparisons; p values were obtained by log-rank analysis.