2016
DOI: 10.18632/aging.101018
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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 homologue PER2, are strongly reduced in primary dermal fibroblasts from aged humans, while raising the expression of PER2 in the sa… Show more

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Cited by 37 publications
(32 citation statements)
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“…Knockdown of Per2 also reduces cellular levels of the Ulk1 protein without affecting Ulk1 mRNA levels, consistent with the rhythmic Ulk1 protein levels and nonrhythmic Ulk1 mRNA levels in these cells 65 . The transient overexpression of Per2 results in the downregulation of the PI3K Class 1/Akt pathway in vitro and increases autophagic flux 65,66 . Tor, ATG5 and ATG7 exhibit rhythmic expression in the brains of wild-type flies under day/night conditions (LD, 12:12), which is abolished in Per1 clock mutants 59 .…”
Section: The Circadian Rhythm Regulates Autophagysupporting
confidence: 73%
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“…Knockdown of Per2 also reduces cellular levels of the Ulk1 protein without affecting Ulk1 mRNA levels, consistent with the rhythmic Ulk1 protein levels and nonrhythmic Ulk1 mRNA levels in these cells 65 . The transient overexpression of Per2 results in the downregulation of the PI3K Class 1/Akt pathway in vitro and increases autophagic flux 65,66 . Tor, ATG5 and ATG7 exhibit rhythmic expression in the brains of wild-type flies under day/night conditions (LD, 12:12), which is abolished in Per1 clock mutants 59 .…”
Section: The Circadian Rhythm Regulates Autophagysupporting
confidence: 73%
“…Per2 in the liver functions as a scaffold protein to tether tuberous sclerosis complex 1 (TSC1), Raptor, and mTOR together to specifically suppress the activity of the mTORC1 complex 64 . Knockdown of Per2 downregulates autophagy levels while leaving core clock oscillations largely intact 65 . Knockdown of Per2 also reduces cellular levels of the Ulk1 protein without affecting Ulk1 mRNA levels, consistent with the rhythmic Ulk1 protein levels and nonrhythmic Ulk1 mRNA levels in these cells 65 .…”
Section: The Circadian Rhythm Regulates Autophagymentioning
confidence: 99%
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“…30 In addition, per2 has also been demonstrated to play a role in cell-autonomous autophagy regulation. 10 Sciarretta et al found that trehalose reduced MI-induced cardiac remodeling and dysfunction through activation of autophagy. 31 In our study, we found that autophagy was increased by overexpression of per2.…”
Section: Discussionmentioning
confidence: 99%
“…Studies have shown that per2 downregulation decreased autophagy levels in fibroblast cells. 10 However, there have been no studies about per2 and myocardial autophagy in the MI model. Autophagy has been demonstrated to play physiological and pathophysiological roles in many kinds of cells and tissues.…”
Section: Introductionmentioning
confidence: 99%