Circadian rhythms and aging.

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The circadian rhythm is a natural, endogenous cycle that lasts ~24 hours that regulates metabolic, physiological, behavioural and cellular activities. This is important for organismal survival. The circadian rhythm is also be entrained and this is important for synchronising internal events with changes in environmental conditions (e.g sunlight).

A robust circadian rhythm is associated with health whilst circadian dysfunction is associated with disease. This is evident from many mouse studies whereby either genetic disruption of "core-clock" components or by artificial manipulation of light/dark cycles that disrupt the circadian rhythm have been associated with shorter lifespans and advanced aging characteristics. Moreever, the robustness of the rhythm has been shown to decline in model organisms with age. There is therefore a lot of interest in understanding how the circadian rhythm can be restored. However, another reason why understanding the circadian clock is important is that the daily changes in organismal activity may mean there could be ideal times of the day when interventions have the greatest effect whilst minimising side effects - this is the premise behind circadian medicine.

So we will first cover what is the circadian rhythm and what it does, we’ll then look at clock dysfunction and studies linking this with shorter lifespan and different diseases. Then we'll see how there is crosstalk between the core clock components and nutrient signalling pathways (mTOR/AMPK/Sirtuins) and finally see how this information could be exploited in circadian medicine, also known a chronotherapeutics.

TIMESTAMPS
Intro - 00:00
Circadian rhythms - 00:44
Core clock components - 03:20
Clock dysfunction & aging - 04:45
Crosstalk with nutrient/longevity signalling pathways - 06:20
Circadian medicine - 08:24

REFERENCES
Acosta-Rodríguez, V.A., Rijo-Ferreira, F., Green, C.B. et al. Importance of circadian timing for aging and longevity. Nat Commun 12, 2862 (2021). https://doi.org/10.1038/s41467-021-22...
Reinke, H., Asher, G. Crosstalk between metabolism and circadian clocks. Nat Rev Mol Cell Biol 20, 227–241 (2019). https://doi.org/10.1038/s41580-018-00...
Deviation of innate circadian period from 24 h reduces longevity in mice - https://doi.org/10.1111/j.1474-9726.2...
Chronic circadian disturbance by a shortened light-dark cycle increases mortality - https://doi.org/10.1016/j.neurobiolag...
TimeTeller: a New Tool for Precision Circadian Medicine and Cancer Prognosis - https://doi.org/10.1101/622050
Universal method for robust detection of circadian state from gene expression - https://doi.org/10.1073/pnas.1800314115
Minimally Invasive Ways of Determining Circadian Rhythms in Humans - https://doi.org/10.1152/physiol.00018...


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