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Timing - Understanding Central and Peripheral Clocks

JM Stepien
JM Stepien
, 
A Coates
A Coates
 and 
S. Banks
S. Banks
   | Sep 01, 2022
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Article Category: review-article
Published Online: Sep 01, 2022
Page range: 19 - 38
DOI: https://doi.org/10.21307/esw-2020-002
Keywords
© 2022 Stepien JM et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1.

The non-visual pathway of light from the environment to the suprachiasmatic nucleus (SCN) and how it regulates the timing of the transcriptional/translational feedback loop (19). Once the light signal reaches the cells of the SCN, it is the induction of Per1 and Per2 gene expression that synchronises SCN timing with the environment.
The non-visual pathway of light from the environment to the suprachiasmatic nucleus (SCN) and how it regulates the timing of the transcriptional/translational feedback loop (19). Once the light signal reaches the cells of the SCN, it is the induction of Per1 and Per2 gene expression that synchronises SCN timing with the environment.

Figure 2.

The differences in the timing of peak Per1 expression in central and peripheral clocks as measured in mice over the 24 hour period drawn from data in Yamanaka et al. (56). This demonstrates that under normal circumstances the timing of Per1 expression in each tissue is not precisely synchronised. Zeitgeber time (ZT) 0 is the time of exposure to the timegiver (in this case time of lights on). SCN=suprachiasmatic nucleus.
The differences in the timing of peak Per1 expression in central and peripheral clocks as measured in mice over the 24 hour period drawn from data in Yamanaka et al. (56). This demonstrates that under normal circumstances the timing of Per1 expression in each tissue is not precisely synchronised. Zeitgeber time (ZT) 0 is the time of exposure to the timegiver (in this case time of lights on). SCN=suprachiasmatic nucleus.

Evidence for the effect of identified entrainers on central and peripheral clock timing in humans and animal models.

Tissue where the clock is found Model Entrainer
Light Activity Temperature Food
SCN Animal Yes No No No (timing)Yes (caloric restriction 66%)
Human Yes Yes (partial) - No (timing)Yes (caffeine)
Liver Animal Yes - rat and mouse Yes - mouse Yes/no - mouse Yes (timing) - rat and mouseYes (caffeine) - mouse
Pineal Gland Animal Yes - rat - - -
Adrenal Gland Animal Yes - rat and mouse - - -
Human Assumed (salivary cortisol) - - -
Heart Animal Yes - rat - - Yes (timing) - rat and mouse
Skeletal Muscle Animal Yes - rat and mouse Yes - mouse - -
Human - Possible - -
Lung Animal Yes - mouse Yes - mouse - Yes (timing) - ratYes (caffeine) - mouse
Hair Follicle Human Yes - - -
Kidney Animal - - No - mouse No (timing) - mouseYes (caffeine) - mouse
Submandibular Gland Animal - - No - mouse -
Pancreas Animal - - - Unsure (timing) - mouse

Human tissues where primary and secondary loop clock gene expression has been measured and the clock genes that were examined.

System Tissue/Cell Clock Gene Measured Reference
Integumentary hair follicle Bmal1Per1 Per2Per3 Rev-ERBαRev-ERBβ (58, 61, 62)
oral mucosa Bmal1Cry1 Per1Per2 Rev-ERBα (57, 63-65)
skin Bmal1 Per1 (57)
skin fibroblasts Bmal1Cry1 Cry2Per1 Per2Per3 (66-69)
skin keratinocytes Bmal1Cry1Cry2 Per 1Per2Per3 Rev-ERBαRORα (69)
skin melanocytes Bmal1Cry1Cry2 Per 1Per2Per3 Rev-ERBα (69)
epidermal stem cells Bmal1Cry1Cry2 Per1Per2Per3 Rev-ERBαRev-ERBβ (59)
Circulatory whole blood ClockBmal1Cry1Cry2 Per1Per2Per3 Rev-ERBαRev-ERBβRORα (70-74)
monocytes ClockBmal1Cry1 Cry2Per1Per2 Per3Rev-ERBα (75)
mononuclear blood cells ClockBmal1Cry1 Cry2Per1Per2α Per3Rev-ERBα (76-85)
leukocytes ClockBmal1Cry1 Cry2Per1Per2 Per3Rev-ERBαRORα (58, 85-91)
lymphocytes ClockBmal1Cry1 Cry2Per1Per2 Per3Rev-ERBα (92)
mast cells ClockBmal1 Cry1Per1 Per2 (93)
eosinophils ClockBmal1 Cry1Per1 Per2 (93)
CD4+ T-cells ClockBmal1Cry1 Cry2Per2Per3 Rev-ERBαRORα (94)
polymorphonuclear cells Cry1Cry2 Per1Per2 Per 3 (83, 85)
papillary muscle cells Bmal1Cry1 Per1Per2 (95)
Endocrine pancreatic islet cells ClockCry1 Per3Rev-ERBα Rev-ERBβ (96)
visceral adipose tissue ClockBmal1 Cry1 Per2 (97, 98)
subcutaneous adipose tissue ClockBmal1 Cry1 Per2 (97, 98)
Bone CD4+ (haematopoietic) bone marrow cells ClockBmal1 Cry1Cry2 Per2Rev-ERBα (99)
whole bone marrow cell samples ClockBmal1 Cry1Cry2 Per2Rev-ERBα (99)
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