Research Paper Volume 8, Issue 9 pp 1876—1895
Crosstalk of clock gene expression and autophagy in aging
- 1 University of Düsseldorf, Medical Faculty, Institute of Clinical Chemistry and Laboratory Diagnostics, 40225 Düsseldorf, Germany
- 2 IUF-Leibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, Germany
Received: May 30, 2016 Accepted: August 18, 2016 Published: August 28, 2016https://doi.org/10.18632/aging.101018
How to Cite
Autophagy and the circadian clock counteract tissue degeneration and support longevity in many organisms. Accumulating evidence indicates that aging compromises both the circadian clock and autophagy but the mechanisms involved are unknown. Here we show that the expression levels of transcriptional repressor components of the circadian oscillator, most prominently the human Period homologue PER2, are strongly reduced in primary dermal fibroblasts from aged humans, while raising the expression of PER2 in the same cells partially restores diminished autophagy levels. The link between clock gene expression and autophagy is corroborated by the finding that the circadian clock drives cell-autonomous, rhythmic autophagy levels in immortalized murine fibroblasts, and that siRNA-mediated downregulation of PER2 decreases autophagy levels while leaving core clock oscillations intact. Moreover, the Period homologue lin-42 regulates autophagy and life span in the nematode Caenorhabditis elegans, suggesting an evolutionarily conserved role for Period proteins in autophagy control and aging. Taken together, this study identifies circadian clock proteins as set-point regulators of autophagy and puts forward a model, in which age-related changes of clock gene expression promote declining autophagy levels.