title: Crosstalk of clock gene expression and autophagy in aging.
abstract: 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 homologuePER2, are strongly reduced in primary dermal fibroblasts from aged humans, while raising the expression ofPER2in 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 ofPER2decreases autophagy levels while leaving core clock oscillations intact. Moreover, the Period homologuelin-42regulates autophagy and life span in the nematodeCaenorhabditis 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.
authors: University of Düsseldorf, Medical Faculty, Institute of Clinical Chemistry and Laboratory Diagnostics, 40225 Düsseldorf, Germany.
authors: Faiza
authors: F
authors: Kalfalah
authors: University of Düsseldorf, Medical Faculty, Institute of Clinical Chemistry and Laboratory Diagnostics, 40225 Düsseldorf, Germany.|IUF-Leibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, Germany.
authors: Linda
authors: L
authors: Janke
authors: University of Düsseldorf, Medical Faculty, Institute of Clinical Chemistry and Laboratory Diagnostics, 40225 Düsseldorf, Germany.|IUF-Leibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, Germany.
authors: Alfonso
authors: A
authors: Schiavi
authors: IUF-Leibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, Germany.
authors: Julia
authors: J
authors: Tigges
authors: University of Düsseldorf, Medical Faculty, Institute of Clinical Chemistry and Laboratory Diagnostics, 40225 Düsseldorf, Germany.
authors: Alexander
authors: A
authors: Ix
authors: University of Düsseldorf, Medical Faculty, Institute of Clinical Chemistry and Laboratory Diagnostics, 40225 Düsseldorf, Germany.|IUF-Leibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, Germany.
authors: Natascia
authors: N
authors: Ventura
authors: University of Düsseldorf, Medical Faculty, Institute of Clinical Chemistry and Laboratory Diagnostics, 40225 Düsseldorf, Germany.
authors: Fritz
authors: F
authors: Boege
authors: University of Düsseldorf, Medical Faculty, Institute of Clinical Chemistry and Laboratory Diagnostics, 40225 Düsseldorf, Germany.|IUF-Leibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, Germany.
authors: Hans
authors: H
authors: Reinke
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D029742:Caenorhabditis elegans Proteins; C400538:LIN-42 protein, C elegans; C421902:PER2 protein, human; D056950:Period Circadian Proteins; D014157:Transcription Factors
keywords: C. elegans; aging; autophagy; circadian clock; lin-42; primary human skin fibroblasts