Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging

Developers

Rachael C. Kuintzle, Eileen S. Chow, Jadwiga M. Giebultowicz, David A. Hendrix, etc.

Description of the technology

Disruption of the circadian clock, which directs rhythmic expression of numerous output genes, accelerates aging. To enquire how the circadian system protects aging organisms, the authors of this technology compare circadian transcriptomes in heads of young and old Drosophila melanogaster. The core clock and most output genes remained robustly rhythmic in old flies, while others lost rhythmicity with age, resulting in constitutive over- or under-expression. Unexpectedly, the authors identify a subset of genes that adopted increased or de novo rhythmicity during aging, enriched for stress-response functions. These genes, termed late-life cyclers, were also rhythmically induced in young flies by constant exposure to exogenous oxidative stress, and this upregulation is CLOCK-dependent. The age-onset rhythmicity was also identified in several putative primary piRNA transcripts overlapping antisense transposons. The received results suggest that, as organisms age, the circadian system shifts greater regulatory priority to the mitigation of accumulating cellular stress.

Practical application

The study, carried out in order to development of this technology, provides first insights into the mechanism of late-life cyclers’ regulation, which involves genes Clock, the rate-limiting master regulator of circadian transcription in Drosophila. These data support a model in which the circadian system enlists late-life cyclers late in life to mitigate damage resulting from potentially diverse sources of cellular and genotoxic stress that accumulate during aging. This technology can be highly valuable for future use in investigations of ageing universal mechanisms of any organisms and development of specific therapy of age-related diseases.

Laboratories

• Department of Biochemistry & Biophysics, 2011 Agriculture & Life Sciences Building, Oregon State University, Corvallis (USA)
• Department of Integrative Biology, 3029 Cordley Hall, Oregon State University, Corvallis (USA)
• School of Electrical Engineering and Computer Science, 1148 Kelley Engineering Center, Oregon State University, Corvallis (USA)

Links

Publications

• Kuintzle, R.C. et al. «Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging." 8 Nature Communications (2017): 14529.
• Krishnan, N. et al. «Loss of circadian clock accelerates aging in neurodegeneration-prone mutants. Neurobiol." 45 Dis. (2012): 1129–1135.
• Krishnan, N. et al. «The circadian clock gene period extends healthspan in aging Drosophila melanogaster." 1 Aging (2009): 937–948.