247MUSCLE: Recent Episodes

Jan-Frieder Harmsen

For details on the podcast, go to 247muscle.com! In this science podcast, your host (Jan-Frieder Harmsen, PhD candidate) interviews scientists, coaches and other practitioners in the field of chronobiology, circadian rhythm, skeletal muscle physiology, exercise performance and sleep. The podcast aims to provide translational knowledge from research findings for students, researchers and the generally interested public.

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Along the ERATO UK - Japan Joint Symposium on Circadian rhythms & Sleep 2024 at the University of Oxford, Dr. John O'Neill (MRC Laboratory of Molecular Biology, Cambridge) was interviewed to discuss his research on the fundamentals of cellular timekeeping. In this second part, John 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 theSCN

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

(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 foodtiming

(0:31:13) How conflicting time cues impair circadianorganization

(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

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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 takes place at the University of Oxford. The symposium aims to promote research exchange and collaboration in the fields of sleep and circadian clocks between the UK and Japan. Prior to the symposium, one of the speakers, Dr. John O'Neill (MRC Laboratory of Molecular Biology, Cambridge), discussed 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 JointSymposium

(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 studycircadian rhythms

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

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

(0:26:23) Almost or all cells in the human bodyhave 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’sactivity

(0:46:49) Outro

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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

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As part of the Daylight Awareness Week (13-17th of November 2023), Prof. Russell Foster (Head of the Nuffield Laboratory of Ophthalmology, and Director of the Sleep and Circadian Neuroscience Institute at the University of Oxford) talks about the differential impact of daylight and electric light on health. In the first part, we cover the basics of how daylight has shaped life on Earth and how it changes over the course of a 24-hour day. Prof. Foster further explains how light sets our inner time, the so-called circadian clock, and how light can influence sleep, alertness, cognitive performance, cardiovascular and metabolic health.

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

Chapters:

(0:00:00) Intro & Daylight Awareness Week

(0:02:20) Topics of this episode series

(0:04:34) Introducing Russell Foster

(0:11:22) Evolution through daylight

(0:16:38) Physical properties of light

(0:26:02) Discovery of how light sets the circadian clock

(0:37:01) Central & peripheral clocks

(0:41:00) Melatonin is the darkness hormone

(0:48:05) Physiological modulation by light

(0:53:05) Outro & Teaser to Part 2

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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.

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Dr. Jorn Trommelen (Assistant Professor, Department of Human Biology, Maastricht University, The Netherlands) talks about his research on pre-sleep protein ingestion after exercise to stimulate muscle protein synthesis. In the first part, we discuss the different forms of proteins and how endurance vs. resistance training differ in their post-exercise protein demand. Jorn further explains why the sleeping period is actually not so different from the awake period with respect to protein needs. We also dive into the details of the main methodological approaches used in Jorn's group to assess muscle protein synthesis.

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In the second part with Prof. Frank Scheer (Division of Sleep and Circadian Disorders, Brigham and Women's Hospital at Harvard Medical School, USA), we discuss what a night-shift worker could consider doing acutely (preceding, during, and following a shift) and chronically (when working yearsof shift schedules) to minimize health risks. In this context, we consider concepts like "sleep banking", when to exercise, caffeine ingestion, what to eat, light exposure strategies & more. We highlight which practical tools are supported by scientific evidence, whereas others seem promising but require further investigation. Lastly, Frank shares his view on how this research field around the health risks of shift work could in the long run achieve guideline changes for shift workers and how labor sectors that are dependent on shift work could be stimulated to improve working conditions.

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Prof. Frank Scheer (Division of Sleep and Circadian Disorders, Brigham and Women's Hospital at Harvard Medical School, USA) introduces us to the topic of shift work and its adverse effects on many health aspects. We define the different forms of shift work with a particular focus on night shifts by painting a picture of what the everyday life of a typical nurse in the hospital looks like, and how working night shift possibly affects her health acutely and in the long term. Thereby, we cover the diverse side-effects of shift work on our physiology and cardiometabolic system as well as associated pathologies. After this general overview, we dive into two recent clinical studies performed by Frank Scheer’s group which focus on the question at what times a shift worker could eat or fast to lower the health burden.

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Dr. Cas Fuchs (Department of Human Biology, Maastricht University, The Netherlands) talks about two of his studies in which he separately investigated the effect of cold- versus hot-water immersion after exercise on recovery. In this context, Cas explains the acute physiological response to cooling and heating. We question what athletes claim or hope to achieve by applying cooling and heating strategies in practice and whether there is scientific evidence behind these claims. The primary focus of Cas' studies is how cooling and heating influence muscle protein synthesis after resistance training and he describes how muscle protein synthesis is measured in his research group. Based on his studies, Cas shares his practical recommendations on who might want to incorporate cooling or heating into his/her exercise routine with specific goals in mind.

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Prof. Alexandra Johnstone (The Rowett Institute, University of Aberdeen, Scotland) talks about her recent study on the timing of calorie loading and its differential effects on weight loss and appetite control. Alex thereby investigated mechanisms behind the diet concept of "eating breakfast like a king". We further discuss the real-world implications of her findings and practical considerations for when to eat most of your calories for different populations.

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In the second part with Dr. Courtney Peterson (Associate Professor at the University of Alabama at Birmingham, USA), we discuss the most recent study published from her laboratory about "Effectiveness of Early Time-Restricted Eating for Weight Loss, Fat Loss, and Cardiometabolic Health in Adults With Obesity - A Randomized Clinical Trial". Subsequently, Courtney points out who should consider practicing time-restricted eating, and whether the early or late form is preferable. In contrast, we also stress that certain populations should be discouraged to practice it.

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Dr. Courtney Peterson (Associate Professor at the University of Alabama at Birmingham, USA) talks about the timing of food intake and how it matters for metabolic and cardiovascular health. Courtney explains the terminology around intermittent fasting & time-restricted eating, complemented by a historical perspective on the scientific literature about how researchers became more and more interested in the timing of food intake. She thereby covers many diet approaches from caloric restriction, breakfast-skipping, "eat breakfast like a king", 1 vs. 2 vs. 3 meals per day to intermittent fasting and time-restricted eating. We discuss the early animal studies that led to the huge increase in clinical human trials about time-restricted eating that we see nowadays. Lastly, we point out potential physiological mechanisms behind the metabolic benefits of time-restricted eating.

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In the second part with Dr. Samer Hattar (Chief of the Section on Light and Circadian Rhythms at the National Institute of Mental Health, Bethesda, MD, USA), we discuss the concept of extraocular phototransduction, meaning how the human body can sense and adjust to light beyond the eyes. We highlight how light at night possibly via impaired sleep can lead to higher appetite & cravings for unhealthy food. Lastly, Samer points out that "Why should I change anything? I sleep well!" people should still reduce light at night to improve health.

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Dr. Samer Hattar (Chief of the Section on Light and Circadian Rhythms at the National Institute of Mental Health, Bethesda, MD, USA) talks about tools to exploit natural daylight and avoid artificial light after sunset to optimize health. Samer shares practical recommendations on how to integrate daylight better into our everyday life. We discuss physiological mechanisms at play how light influences human physiology. We extensively cover the topic of blue-blocking glasses, which can be a good or a bad thing depending on time of day, and elaborate on differences between glasses. We further acknowledge many things that we don't know about how light influences us humans.

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Your host Frieder introduces the topic of light and its influence on human physiology. Properties of light, such as the visible wavelength spectrum of light as well as ultra-violett (UV) and infrared light, are described. Differences between natural daylight and electric artificial light are pointed out. Time-of-day dependency of the influence of light on physiology is highlighted with a special focus on the secretion of the "darkness hormone" melatonin. Practical recommendations on how 24h light exposure can support wakefulness, sleep and overall health are mentioned and will be further discussed in the upcoming episodes with future guests. Frieder also presents his recent study on how an indoor 24h light scheme mimicking the natural light/dark cycle more closely influences metabolic health and thermoregulation in older volunteers with pre-diabetes.

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M.Sc. Saar Ezagouri (Gad Asher's Lab, Weizmann Institute of Science, Rehovot, Israel) talks about his study on daily variance in exercise capacity, in which he showed that mice as well as humans have a higher capacity to perform moderate intensity endurance exercise in their respective late activity phase of the day, corresponding to evening hours in humans. We discuss the role of the molecular clock, liver glycogen, and other mechanisms underlying this daily variation. We also address potential practical implications of theses findings in everyday life and whether the general population should worry about when to perform workouts for general health purposes.

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Dr. Nicholas Saner (Baker Heart and Diabetes Institute, Melbourne, Australia) talks about his study on how exercise can reduce the negative metabolic impact of sleep restriction. We discuss the overall role of mitochondria in skeletal muscle for metabolic health and zoom into his findings on mitochondrial respiration and sarcoplasmic protein synthesis after sleep restriction in combination with exercise. We elaborate on potential practical implications for shift workers and the general population suffering from sleep restriction.

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Dr. Jonathan Cedernaes (Northwestern University and Uppsala University) talks about the acute effects of sleep loss on skeletal muscle, adipose tissue and glucose metabolism. Sleep loss is associated with weight gain and loss of muscle mass in humans and insufficient sleep is considered a risk factor to develop obesity and metabolic diseases. We discuss Dr. Cedernaes' recent findings on the molecular changes in muscle and adipose tissue possibly underlying the negative metabolic impact of sleep loss.

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Prof. Karyn Esser from the University of Florida introduces the circadian clock present in skeletal muscle. We discuss how muscle clocks... work when comparing mice that are active at night to humans that are active during the day; influence metabolism and exercise performance; can be altered by environmental factors such as light, temperature, food intake and muscle contractions at different times of the day; are possibly involved in the development of type 2 diabetes and are affected by alcohol intake.

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In this episode, Frieder introduces the general idea of the 247MUSCLE podcast and himself.