Expression profiling by high throughput sequencing
Summary
Organisms use endogenous clocks to adapt to the rhythmicity of the environment and to synchronize social activities. Although circadian rhythms have been implicated in multiple aspects of aging, it remains uncertain whether evolutionary selection of circadian cycle gene variants contributes to changes in longevity and aging traits within animal populations. We have sequenced the genomes of Drosophila melanogaster strains with exceptional longevity that were obtained via multiple rounds of selection for reduced senescence from a parental strain. Preservation of youthful muscle gene expression and function is seen during aging in these strains and is primarily due to intergenic polymorphisms rather than to mutations in coding sequences. Expression of transcriptional regulators of the circadian machinery is highly modulated, with higher period and timeless and lower cycle expression in strains with delayed aging compared to the parental strain. These changes in the expression of circadian core components associate with changes in the amplitude and specificity of the circadian transcriptome. Moreover, a muscle-specific increase in timeless expression to levels similar to long-lived lines extends lifespan. Altogether, these findings indicate that circadian clock gene variants contribute to shaping aging traits and to the evolutionarily divergence in longevity within a species.
Overall design
Muscle samples of 3 strains, 2 of which show delayed aging (O1 and O3, O for old) relative to the parental strains (B3, B for Base) showing divergence at 1 and 6 weeks of age. Also included are data from transgenic lines with muscle specific expression of timeless (Mhc>timeless) and a control set (mhc, for Mhc-Gal4 transgene) showing divergent circadian rhythms when measured at 0, 6 12 and 18 hrs.
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