Dr. Victoria Acosta-Rodriguez (Leader of the Circadian Biology of Aging Unit at the National Institute on Aging (NIA), USA) talks about her research on longevity and caloric restriction. In this first part, Victoria introduces us to longevity research: what kind of interventions and drugs are known to promote longevity and why precise terminology separating life- and healthspan is important. We discuss how the lifespan of mice relates to the lifespan of humans and to what degree we can therefore translate mice studies to the human setting. As we will learn, one intervention to promote longevity is caloric restriction, that is why Victoria also summarizes our current understanding of caloric restriction and defines its different forms.

Chapters:

(00:00:45) Podcast name and host updates

(00:02:51) Introducing Victoria Acosta-Rodriguez

(00:04:43) Interview start

(00:05:26) Victoria’s personal background

(00:09:04) Terminology: Lifespan vs. healthspan

(00:12:25) What interventions promote longevity?

(00:17:24) Defining caloric restriction

(00:21:57) Relevance of feeding time for mice

(00:30:12) Mice vs. humans for longevity studies

(00:38:25) Changes in circadian rhythms upon aging?

(00:44:26) Outro

Main study that we will discuss in depth:

Acosta-Rodriguez, V., Rijo-Ferreira, F., Izumo, M., Xu, P., Wight-Carter, M., Green, C.B., and Takahashi, J.S. (2022). Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice. Science 376, 1192-1202. 10.1126/science.abk0297.

Additional papers that Victoria refers to:

Mice - time-restricted feeding, regular chow

Damiola, F., Le Minh, N., Preitner, N., Kornmann, B., Fleury-Olela, F., and Schibler, U. (2000). Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev 14, 2950-2961.

Mice - on a high-fat diet & time-restricted feeding

Kohsaka, A., Laposky, A.D., Ramsey, K.M., Estrada, C., Joshu, C., Kobayashi, Y., Turek, F.W., and Bass, J. (2007). High-fat dietcdisrupts behavioral and molecular circadian rhythms in mice. Cell Metab 6, 414-421. 10.1016/j.cmet.2007.09.006.

Arble, D.M., Bass, J., Laposky, A.D., Vitaterna, M.H., and Turek, F.W. (2009). Circadian timing of food intake contributes to weight gain. Obesity (Silver Spring) 17, 2100-2102. 10.1038/oby.2009.264.

Vollmers, C., Gill, S., DiTacchio, L., Pulivarthy, S.R., Le, H.D., and Panda, S. (2009). Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression. Proc Natl Acad Sci U S A 106, 21453-21458. 10.1073/pnas.0909591106.

Hatori, M., Vollmers, C., Zarrinpar, A., DiTacchio, L., Bushong, E.A., Gill, S., Leblanc, M., Chaix, A., Joens, M., Fitzpatrick, J.A., et al. (2012). Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab 15, 848-860. 10.1016/j.cmet.2012.04.019.

Mice -Calories, Fasting & important variables influencing Lifespan

Mitchell, S.J., Bernier, M., Mattison, J.A., Aon, M.A., Kaiser, T.A., Anson, R.M., Ikeno, Y., Anderson, R.M., Ingram, D.K., and de Cabo, R. (2019). Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories. Cell Metab 29, 221-228 e223. 10.1016/j.cmet.2018.08.011.

Mitchell, S.J., Madrigal-Matute, J., Scheibye-Knudsen, M., Fang, E., Aon, M., Gonzalez-Reyes, J.A., Cortassa, S., Kaushik, S., Gonzalez-Freire, M., Patel, B., et al. (2016). Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice. Cell Metab 23, 1093-1112. 10.1016/j.cmet.2016.05.027.

Acosta-Rodriguez, V.A., de Groot, M.H.M., Rijo-Ferreira, F., Green, C.B., and Takahashi, J.S. (2017). Mice under Caloric Restriction Self-Impose a Temporal Restriction of Food Intake as Revealed by an Automated Feeder System. Cell Metab 26, 267-277 e262. 10.1016/j.cmet.2017.06.007.

Acosta-Rodriguez, V.A., Rijo-Ferreira, F., Green, C.B., and Takahashi, J.S. (2021). Importance of circadian timing for aging and longevity. Nat Commun 12, 2862. 10.1038/s41467-021-22922-6.

From the 11th to the 13th of March 2024, the 247Muscle podcast has been invited to cover the ERATO UK - Japan Joint Symposium on Circadian rhythms & Sleep, which took place at the University of Oxford. The symposium aimed to promote research exchange and collaboration in the fields of sleep and circadian clocks between the UK and Japan. In this episode, your host Frieder summarizes scientific insights from the symposium and shares short interviews conducted with speakers during the symposium.

More information about the ERATO UK - Japan Joint Symposium: https://sys-pharm.m.u-tokyo.ac.jp/erato-uk/

Chapters:

(00:00:54) Background of the ERATO symposium

(00:02:40) Introduction by Hiroki Ueda

(00:07:25) Summary of the welcome ceremony

(00:10:03) Russell Foster on EEG and large sleep databases

(00:12:19) Wearables to measure sleep

(00:15:20) Andrew Millar on plant vs. human clocks and metabolism

(00:25:05) The concept of “Arrival” for circadian research

(00:36:35) Historical perspective on sleep research

(00:39:47) Anne Skeldon on mathematical models for sleep

(00:41:12) Koji Ode on CaMK2

(00:47:14) Hiroyuki Kanaya on anesthetics

(00:49:55) Akifumi Kishi on human sleep phenotypes

(00:50:44) Amin Mottahedin on stroke time

(00:53:01) Alex Webb on chronoculture and space culturing

(00:56:15) Sleep restriction therapy

(01:00:44) Attendants and organizers sharing their highlights

(01:07:48) Future perspective

(01:13:17) Closing remarks

(01:14:23) Sponsor: Mitsui Chemicals

(01:15:54) Outro

In this second part, Dr. John O'Neill (MRC Laboratory of Molecular Biology, Cambridge) provides deep insights from his recent study on how the timing of food intake mechanistically modifies circadian clocks in cells and animals. He explains the research journey of how his group identified systemic time cues associated with food intake. John highlights the indispensable role of the vital protein kinase called mTOR for the cell to process the timing of food intake. Lastly, we discuss how the mechanistic knowledge from John's research might translate to practical eating strategies for shiftwork and jetlag.

More information about the ERATO UK - Japan Joint Symposium: https://sys-pharm.m.u-tokyo.ac.jp/erato-uk/

Chapters:

(0:00:11) Intro

(0:02:23) Food-entrainable oscillator?

(0:06:06) How insulin emerged as a suspect

(0:08:38) Food timing entrains all cell clocks except for the SCN

(0:10:32) What other candidates than insulin were considered?

(0:12:29) How insulin modifies clocks

(0:16:35) Insulin action in vitro vs. in vivo

(0:25:07) Why the SCN remains mostly irresponsive to food timing

(0:31:13) How conflicting time cues impair circadian organization

(0:34:38) What about skipping breakfast?

(0:39:07) The role of meal frequency and snacking

(0:42:39) Combining time cues to support health

(0:45:37) The role of mTor in daily cellular timekeeping

(0:48:33) Translational perspective on shift work

(0:55:15) John’s recommendations to reduce jetlag

(0:58:05) John’s perspective on the ERATO symposium

(1:01:20) John’s future research

(1:05:20) John’s career ambitions

(1:08:01) Funny anecdote

(1:12:09) Outro

Dr. John O'Neill (MRC Laboratory of Molecular Biology, Cambridge), discusses his research focusing on the fundamentals of cellular timekeeping. In this first part, John explains the advantages of cells as a model to study circadian rhythms. He provides evidence of why we might consider questioning the current paradigm of how cells keep time, since his group for example demonstrated that even cells without nuclei show circadian rhythms. We further highlight a fascinating study in fibroblasts showing that wounds heal much faster when inflicted during the day vs. night. Lastly, John shares his knowledge of the vital protein kinase called mTOR, and its role in daily physiology.

More information about the ERATO UK - Japan Joint Symposium: https://sys-pharm.m.u-tokyo.ac.jp/erato-uk/

Chapters:

(0:00:28) Introducing ERATO UK/Japan Joint Symposium

(0:03:15) This episode’s guest and content

(0:05:43) Dr. John O’Neill introduces himself

(0:07:46) Advantages of cells as a model to study circadian rhythms

(0:11:11) Challenging our current understanding on how cells keep time

(0:18:47) How do known time cues translate into cellular signals?

(0:26:23) Almost or all cells in the human body have a clock?

(0:29:01) Day-night rhythms in wound healing

(0:37:02) mTOR’s role in physiology

(0:43:23) Activators and inhibitors of mTOR

(0:45:41) Daily and intrinsic rhythms in mTOR’s activity

(0:46:49) Outro

In the second part with Prof. Russell Foster (Head of the Nuffield Laboratory of Ophthalmology, and Director of the Sleep and Circadian Neuroscience Institute at the University of Oxford), contributing to the Daylight Awareness Week (13-17th of November 2023), we continue our discussion around the differential impact of daylight and electric light on health. We provide a historical perspective about human inventions that aimed to end the dependency on daylight - from fire to electric lighting. Prof. Foster further shares practical recommendations on how daylight and electric light can support health and well-being. Lastly, he gives an outlook on where the research around lighting and health is heading to in the future.

More information about the Daylight Awareness Week: ⁠https://daylight.academy/daylight-awareness-week-2023/

Chapters:

(0:00:00) Intro & Recap of Part 1

(0:02:36) History of inventing fire & candles

(0:08:22) Rise of electric light & disruption

(0:15:15) Sensitivity to light at night

(0:22:03) Dominance of LEDs nowadays

(0:23:07) Interim conclusion

(0:27:18) Practical recommendations for evening lighting

(0:30:37) Architectural dilemma with daylight

(0:33:12) Early birds vs. Night owls

(0:37:35) Jet lag

(0:40:10) Drug development for blind people

(0:42:11) Mimick seasonal changes in daylight

(0:45:29) Russell’s personal outlook

(0:55:02) Funny anecdotes

(0:59:26) Outro

Papers/books that Russell refers to:

A. Roger Ekirch's book: “At Day's Close”

Thomas Wehr's research on bimodal or polymodal sleep:

"In short photoperiods, human sleep is biphasic" (Wehr 1992)

https://doi.org/10.1111/j.1365-2869.1992.tb00019.x

Russell's group - investigation on international populations, night owls were missing morning light

"Chronotype and environmental light exposure in a student population" (Porcheret et al. 2018)

https://doi.org/10.1080/07420528.2018.1482556

Charles Czeisler’s group - full-intensity kindle watching for 4 hours for 5 nights

"Evening use of light-emitting eReaders negatively affects sleep, circadian timing, and next-morning alertness" (Chang et al. 2014)

https://doi.org/10.1073/pnas.1418490112

Prior light exposure of 500-600 lux during the day abolished the suppressing-melatonin-effect

"The effects of prior light history on the suppression of melatonin by light in humans" (Hebert et al. 2002)

https://doi.org/10.1034%2Fj.1600-079x.2002.01885.x

Harvard group: aged humans show decreased sensitivity to light

"Decreased sensitivity to phase-delaying effects of moderate intensity light in older subjects" (Duffy et al. 2007)

https://doi.org/10.1016/j.neurobiolaging.2006.03.005

Christian Cajochen’s work on alertness, blue light is most important

"High Sensitivity of Human Melatonin, Alertness, Thermoregulation, and Heart Rate to Short Wavelength Light" (Cajochen et al. 2005)

https://pubmed.ncbi.nlm.nih.gov/15585546/

Arti Jagannath's work on jet lag:

SIK1 deletion in mice and jet lag:

"The CRTC1-SIK1 pathway regulates entrainment of the circadian clock" (Jagannath et al. 2013)

https://doi.org/10.1016/j.cell.2013.08.004

Recent review on SIK:

"The multiple roles of salt-inducible kinases in regulating physiology" (Jagganath et al. 2023)

https://doi.org/10.1152/physrev.00023.2022

How to contact Russell Foster:

Email: russell.foster@eye.ox.ac.uk

In the second part with Dr. Jorn Trommelen (Assistant Professor, Department of Human Biology, Maastricht University, The Netherlands), we talk about Jorn's recent study on pre-sleep protein ingestion after acute endurance exercise to stimulate muscle protein synthesis. Jorn explains how these findings from acute studies relate to boosting long-term gains in strength, hypertrophy and endurance performance in response to regular pre-sleep protein ingestion. Based on his studies, Jorn shares his view on practical recommendations for pre-sleep protein in endurance- and resistance-training types of sports.

Main paper that we discuss in depth:

Pre‐sleep Protein Ingestion Increases Mitochondrial Protein Synthesis Rates During Overnight Recovery from Endurance Exercise: A Randomized Controlled Trial (Trommelen et al. 2023)

https://link.springer.com/article/10.1007/s40279-023-01822-3

Additional papers that Jorn refers to:

Long-term study on pre-sleep protein for muscle gains:

Protein Ingestion before Sleep Increases Muscle Mass and Strength Gains during Prolonged Resistance-Type Exercise Training in Healthy Young Men (Snijders et al. 2015)

https://pubmed.ncbi.nlm.nih.gov/25926415/

How to contact Jorn Trommelen:

Twitter: @JornTrommelen

Website: nutritiontactics.com

Instagram: @nutritiontactics

LinkedIn: https://www.linkedin.com/in/jorntrommelen/

Email: jorn.trommelen@maastrichtuniversity.nl