Uploaded July 2021 | Updated September 2026, 3 weeks ago
SPONSOR - Longevity.Technology https://www.longevity.technology/?utm_source=SSS&utm_medium=YouTube&utm_campaign=CircadianRhythms
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). doi.org/10.1038/s41467-021-22922-6
Reinke, H., Asher, G. Crosstalk between metabolism and circadian clocks. Nat Rev Mol Cell Biol 20, 227–241 (2019). doi.org/10.1038/s41580-018-0096-9
Deviation of innate circadian period from 24 h reduces longevity in mice - doi.org/10.1111/j.1474-9726.2012.00846.x
Chronic circadian disturbance by a shortened light-dark cycle increases mortality - doi.org/10.1016/j.neurobiolaging.2011.11.005
TimeTeller: a New Tool for Precision Circadian Medicine and Cancer Prognosis - doi.org/10.1101/622050
Universal method for robust detection of circadian state from gene expression - doi.org/10.1073/pnas.1800314115
Minimally Invasive Ways of Determining Circadian Rhythms in Humans - doi.org/10.1152/physiol.00018.2020
Check out @LongevityScienceNews latest video -
Icons in intro; "freepik.com/free-photos-vectors/background"Background vector created by freepik - freepik.com
SPONSOR - Longevity.Technology https://www.longevity.technology/?utm_source=SSS&utm_medium=YouTube&utm_campaign=CircadianRhythms
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). doi.org/10.1038/s41467-021-22922-6
Reinke, H., Asher, G. Crosstalk between metabolism and circadian clocks. Nat Rev Mol Cell Biol 20, 227–241 (2019). doi.org/10.1038/s41580-018-0096-9
Deviation of innate circadian period from 24 h reduces longevity in mice - doi.org/10.1111/j.1474-9726.2012.00846.x
Chronic circadian disturbance by a shortened light-dark cycle increases mortality - doi.org/10.1016/j.neurobiolaging.2011.11.005
TimeTeller: a New Tool for Precision Circadian Medicine and Cancer Prognosis - doi.org/10.1101/622050
Universal method for robust detection of circadian state from gene expression - doi.org/10.1073/pnas.1800314115
Minimally Invasive Ways of Determining Circadian Rhythms in Humans - doi.org/10.1152/physiol.00018.2020
Check out @LongevityScienceNews latest video -
Icons in intro; "freepik.com/free-photos-vectors/background"Background vector created by freepik - freepik.com










![the 3 levels of aging therapeutics
Why do so many anti-aging drugs work in mice but fail in humans? It turns out, we might be aging in fundamentally different ways. A new minimal model from physicists Peter Fedichev and Jan Gruber suggests that aging isnt a chaotic mess of billions of problems, but a process governed by just three macroscopic variables.
In this video, I break down their paper to explain why current Level 1 interventions (like senolytics and cellular reprogramming) might only improve healthspan, not maximum lifespan. Well explore the difference between stable species (humans) and unstable ones (mice), and reveal the physics-based roadmap—Level 2 and Level 3—required to actually extend the human lifespan limit beyond 120 years.
Find me on Twitter - https://twitter.com/EleanorSheekey
Support the channel
through PayPal - https://paypal.me/sheekeyscience?country.x=GB&locale.x=en_GB
through Patreon - https://www.patreon.com/TheSheekeyScienceShow
TIMESTAMPS
0:00 – Why 300 aging theories might be wrong (The Physics of Universality)
3:45 – The 3 variables that control your lifespan
7:12 – Why mice are biologically broken compared to humans
9:58 – The 3 Levels of Intervention: Why reprogramming isnt enough (yet)
13:20 – The only way to actually break the 120-year limit
REFERENCES
Fedichev, P. & Gruber, J. (2024). A Minimal Model Explains Aging Regimes and Guides Intervention Strategies. bioRxiv. [Preprint]
Pyrkov, T. V., et al. (2021). Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts ultimate limit of human lifespan. Nature Communications, 12, 2765.
Avchaciov, K., et al. (2022). Unsupervised learning of aging principles from longitudinal data. Nature Communications, 13, 6529.
Perevoshchikova, K. & Fedichev, P. O. (2024). Differential Responses of Dynamic and Entropic Aging Factors to Longevity Interventions. bioRxiv.
Tarkhov, A. E., et al. (2024). Universal transcriptomic signature of age reveals the temporal scaling of Caenorhabditis elegans aging trajectories. AgingBio, 2, 1–16.
Tong, H., et al. (2024). Quantifying the stochastic component of epigenetic aging. Nature Aging, 4, 886–897.
Meyer, D. H. & Schumacher, B. (2024). Biologically informative or merely random? The stochastic nature of epigenetic clocks. Nature Aging, 4, 871–885.
Sinclair, D. A. & Guarente, L. (1997). Extrachromosomal rDNA circles—a cause of aging in yeast. Cell, 91(7), 1033–1042.
Medvedev, Z. A. (1990). An attempt at a rational classification of theories of ageing. Biological Reviews, 65(3), 375–398.
Please note that The Sheekey Science Show is distinct from Eleanor Sheekeys teaching and research roles. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Sheekey Science Show and guests assume no liability for the application of the information discussed.
Icons in intro; https://www.freepik.com/free-photos-vectors/backgroundBackground vector created by freepik - www.freepik.com the 3 levels of aging therapeutics](https://i.ytimg.com/vi/c-_Pdp5IIvw/mqdefault.jpg)