Biochemistry & Biophysics
A robust circadian clock is well known to be an integral part of healthy aging. Senescent flies and mammals exhibit irregular behavioral and sleep rhythms, which are associated with neurodegeneration and increased susceptibility to oxidative stress. In flies, these phenotypes are exacerbated in clock gene mutants, suggesting that the ability to maintain strong clock function may slow down aging and extend healthspan. However, the molecular basis for age-related circadian dysregulation is unknown. To investigate this, we performed RNA sequencing (RNA-Seq) and compared the temporal expression profiles of circadian transcripts in young and old Drosophila melanogaster. Our hypothesis that aging of the circadian clock may lead to dampened oscillations in the expression of clock-controlled genes was supported by a large group of genes which lose amplitude or become arrhythmic in old flies. Unexpectedly, we also identified a subset of genes which are arrhythmic in young flies but adopt a rhythmic expression pattern during aging. Our data also revealed a potential novel, multi-exonic, age-activated noncoding gene with rhythmic expression. This study demonstrates extensive and diverse effects of aging on rhythmic RNA levels and provides a genome-wide map of isoform-resolution expression in senescent Drosophila.