CHRONO:MEDICINE (Dr. Jan-Frieder Harmsen)

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.

Main paper that we discuss:

Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans

https://www.science.org/doi/10.1126/sciadv.aar8590

Other papers that Jonathan refers to:

Research from Jonathan's grandfather Lennart Wetterberg

https://link.springer.com/chapter/10.1007/978-3-7091-4427-5_22

https://www.sciencedirect.com/science/article/abs/pii/0306453079900052

https://www.sciencedirect.com/science/article/abs/pii/S0079612308629623

https://pubmed.ncbi.nlm.nih.gov/?term=wetterberg+melatonin&filter=years.1970-1980&sort=date&size=100

Effects of Sleep Fragmentation on Glucose Metabolism in Normal Subjects

https://www.sciencedirect.com/science/article/pii/S0012369210600207?casa_token=q3z3AAL0Gc8AAAAA:xabjyqwSYjXm6J6eD2ba0hbVFwnfqGawDtfnzny1cxjhqDcA3jTethQcMRU8Rj7K15iNCv8s

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans (Scheer's group, Morris et al. 2015)

https://www.pnas.org/content/112/17/E2225.short

Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep (van Cauter et al. 1991)

https://www.jci.org/articles/view/115396

Sleep disturbances compared to traditional risk factors for diabetes development: Systematic review and meta-analysis (Anothaisintawee et al. 2016)

https://www.sciencedirect.com/science/article/pii/S108707921500146X?casa_token=qZDfPyRRA0AAAAAA:6Bxx4awODsQ885WNcRw3HK5Q8PevE_MbWtaRfTb9PPd-0M3T7AFH0RUMBVaxg600HKlphdOC

Acute exercise remodels promoter methylation in human skeletal muscle (Barres et al. 2012)

https://pubmed.ncbi.nlm.nih.gov/22405075/

Insufficient sleep undermines dietary efforts to reduce adiposity (Nedeltcheva et al. 2010)

https://pubmed.ncbi.nlm.nih.gov/20921542/

Correlation Patterns Between DNA Methylation and Gene Expression in The Cancer Genome Atlas (Spainhour et al. 2019)

https://journals.sagepub.com/doi/full/10.1177/1176935119828776

Effects of Posture on Gastric Emptying, Transpyloric Flow, and Hunger After a Glucose Drink in Healthy Humans (Jones et al. 2006)

https://link.springer.com/article/10.1007/s10620-005-9010-3

Right recumbent position on gastric emptying of water evidenced by 13C breath testing (Sanaka et al. 2013)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554820/

Resetting of Circadian Time in Peripheral Tissues by Glucocorticoid Signaling (Balsalobre et al. 2000)

https://www.science.org/doi/full/10.1126/science.289.5488.2344

Circadian Clock NAD+ Cycle Drives Mitochondrial Oxidative Metabolism in Mice (Peek et al. 2013)

https://www.science.org/doi/full/10.1126/science.1243417

Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms (Saner et al. 2020)

https://www.sciencedirect.com/science/article/pii/S2212877820301848

Paradoxical sleep deprivation induces muscle atrophy (Dattilo et al. 2011)

https://onlinelibrary.wiley.com/doi/full/10.1002/mus.22322?casa_token=adEkbMYydf8AAAAA%3APgqChN4d-wpcDWvYUmzbGmNGC1hx6XfYk0OxTVzpJ_pf06x9I7pXxwBuKWoS-f43GLbtXKUTl8QRnTK7dw

Leucine supplementation is anti-atrophic during paradoxical sleep deprivation in rats (Souza et al. 2016)

https://link.springer.com/article/10.1007/s00726-015-2142-7

Circadian clock-dependent and -independent rhythmic proteomes implement distinct diurnal functions in mouse liver (Mauvoisin et al. 2014)

https://www.pnas.org/content/111/1/167.short

Effects of Sleep Fragmentation on Glucose Metabolism in Normal Subjects (Stamatakis et al. 2010) https://www.sciencedirect.com/science/article/abs/pii/S0012369210600207

Impact of Untreated Obstructive Sleep Apnea on Glucose Control in Type 2 Diabetes (Aronsohn et al. 2009)

https://www.atsjournals.org/doi/full/10.1164/rccm.200909-1423OC

Sleep Apnea and Glucose Metabolism: A Long-term Follow-up in a Community-Based Sample (Lindberg et al. 2012)

https://www.sciencedirect.com/science/article/abs/pii/S0012369212605625

Jonathan Cedernaes on Social Media:

Twitter: @JCedernaes, @SRBR_Outreach

Homepage: drcedernaes.com

at Uppsala University (Sweden): https://katalog.uu.se/profile/?id=N7-789

at Northwestern University (USA): https://northwestern.academia.edu/JonathanCedernaes

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.

Main papers that we discuss:

1. Ticking for Metabolic Health: The Skeletal-Muscle Clocks https://onlinelibrary.wiley.com/doi/10.1002/oby.22826

2. Time-of-day dependent effects of contractile activity on the phase of the skeletal muscle clock

https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP279779

3. Binge alcohol disrupts skeletal muscle core molecular clock independent of glucocorticoids

https://journals.physiology.org/doi/full/10.1152/ajpendo.00187.2021

Other papers that Karyn refers to:

Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock https://pubmed.ncbi.nlm.nih.gov/24567902/

How jet lag impairs Major League Baseball performance https://www.pnas.org/content/114/6/1407.long

Diurnal Differences in Human Muscle Isometric Force In Vivo Are Associated with Differential Phosphorylation of Sarcomeric M-Band Proteins https://www.mdpi.com/2227-7382/8/3/22

Karyn Esser on Social Media:

Twitter: @kaesser

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.

Main paper:

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:

Yves Boirie, guy who invented the cow model

First study about production of the labeled milk:

Production of large amounts of [13C]leucine-enriched milk proteins by lactating cows (Boirie et al. 1995)

https://pubmed.ncbi.nlm.nih.gov/7815181/

First paper applying the model:

Slow and fast dietary proteins differently modulate postprandial protein accretion (Boirie et al. 1997)

https://pubmed.ncbi.nlm.nih.gov/9405716/

Paper from Jorn's group applying the model:

Ingestion of Free Amino Acids Compared with an Equivalent Amount of Intact Protein Results in More Rapid Amino Acid Absorption and Greater Postprandial Plasma Amino Acid Availability Without Affecting Muscle Protein Synthesis Rates in Young Adults in a Double-Blind Randomized Trial (Weijzen et al. 2022)

https://pubmed.ncbi.nlm.nih.gov/34642762/

Jorn's review on this model:

Comprehensive assessment of post-prandial protein handling by the application of intrinsically labelled protein in vivo in human subjects (Trommelen et al. 2021)

https://pubmed.ncbi.nlm.nih.gov/33487181/

Literature for peak times in myofibrillar vs. mitochondrial protein synthesis after exercise:

"Whereas myofibrillar protein synthesis rates are typically highest during acute post-exercise recovery (0–6 h) [28, 29], mitochondrial protein synthesis rates appear to peak at ~ 24 h of post-exercise recovery [25, 27, 30]. Therefore, it could be speculated that post-exercise protein ingestion may prove to be more effective at stimulating mitochondrial protein synthesis rates when assessed over a more prolonged recovery period [31]."

!See numbered references in the main paper stated above!

Generally 20g of protein maximally stimulates muscle protein synthesis:

Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men (Moore et al. 2009)

https://pubmed.ncbi.nlm.nih.gov/19056590/

Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise (Witard et al. 2014)

https://pubmed.ncbi.nlm.nih.gov/24257722/

Presleep dietary protein-derived amino acids are incorporated in myofibrillar protein during postexercise overnight recovery (Trommelen et al. 2018)

https://pubmed.ncbi.nlm.nih.gov/28536184/

Studies of protein’s impact on sleep

Protein intake and its effect on sleep outcomes: a systematic review and meta-analysis of randomized controlled trials (Wirth et al. 2023) https://academic.oup.com/nutritionreviews/article/81/3/333/6694939?login=true

Protein Ingestion before Sleep Increases Overnight Muscle Protein Synthesis Rates in Healthy Older Men: A Randomized Controlled Trial (Kouwe et al. 2017)

https://pubmed.ncbi.nlm.nih.gov/28855419/

How to contact Jorn Trommelen:

Twitter: @JornTrommelen

Website: nutritiontactics.com

Instagram: @nutritiontactics

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

Email: jorn.trommelen@maastrichtuniversity.nl

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.

Contact: Dr. Victoria Acosta-Rodriguez

Email: ⁠victoria.acosta-rodriguez@nih.gov⁠

Twitter/X: @VickyAcostaR

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.

Main paper:

Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes (Sutton et al. 2018)

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30253-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413118302535%3Fshowall%3Dtrue

Additional papers that Courtney and I refer to:

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake (Anson et al. 2003)

https://www.pnas.org/doi/abs/10.1073/pnas.1035720100

Time-Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet (Hatori et al. 2012)

https://www.sciencedirect.com/science/article/pii/S1550413112001891

Oren Froy's group in Israel:

Timed high-fat diet resets circadian metabolism and prevents obesity (Sherman et al. 2012)

https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.12-208868

Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice (Acosta-Rodriguez et al. 2022)

https://www.science.org/doi/10.1126/science.abk0297

Rafael de Cabo's group:

Caloric restriction improves health and survival of rhesus monkeys (Mattison et al. 2017)

https://www.nature.com/articles/ncomms14063

Time-Restricted Eating to Prevent and Manage Chronic Metabolic Diseases (Chaix et al. 2019)

https://www.annualreviews.org/doi/10.1146/annurev-nutr-082018-124320

Mark Mattson's group:

A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults (Stote et al. 2007)

https://academic.oup.com/ajcn/article/85/4/981/4648934

Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women (Carlson et al. 2007) https://www.sciencedirect.com/science/article/abs/pii/S0026049507002806

High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women (Jakubowicz et al. 2013)

https://onlinelibrary.wiley.com/doi/full/10.1002/oby.20460

Restore fertility in women struggling to ovulate by frontloading calories early in the day:

Effects of caloric intake timing on insulin resistance and hyperandrogenism in lean women with polycystic ovary syndrome (Jakubowicz et al. 2013)

https://portlandpress.com/clinsci/article-abstract/125/9/423/69160/Effects-of-caloric-intake-timing-on-insulin

Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep. (Van Cauter et al. 1991)

https://www.jci.org/articles/view/115396

Diurnal Variation of Oral Glucose Tolerance: a Possible Pointer to the Evolution of Diabetes Mellitus (Jarret & Keen 1969)

https://doi.org/10.1136/bmj.2.5653.341

Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity (Carrasco-Benso et al. 2016)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001513/

Rodents show better sodium secretion earlier in the day (work in progress from David Pollock's lab)

Effect of skipping breakfast for 6 days on energy metabolism and diurnal rhythm of blood glucose in young healthy Japanese males (Ogata et al. 2019)

https://academic.oup.com/ajcn/article/110/1/41/5490310

Cardiometabolic effects of early v. delayed time-restricted eating plus energetic restriction in adults with overweight and obesity: an exploratory randomised clinical trial (Queiroz et al. 2022)

https://pubmed.ncbi.nlm.nih.gov/35614845/

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 Prof. Christian Cajochen (Head of the Centre for Chronobiology at the University of Basel in Switzerland), contributing to the Daylight Awareness Week (28th of October - 2nd of November 2024), we continue our discussion around the impact of daylight on our health, with a special focus on sleep. Christian summarizes the negative effects of bright electric light exposure on sleep and other health outcomes. On the other hand, he highlights the importance of daylight and alternatively increased electric light intensities during daytime for sleep. We also discuss how seasonal changes in daylight affect us more than we think. Christian gives insights into a real-world example of how switching to dynamic lighting at the workplace changed people’s wellbeing. And lastly, we discuss if a medical pill could eventually replace the health effects of daylight.

More information about the Daylight Awareness Week: ⁠https://daylight.academy/daylight-awareness-week-2024/⁠

Chapters:

(0:00:12) Intro & Daylight Awareness Week

(0:00:48) Topics of this episode series

(0:02:13) Introduction to sleep

(0:04:15) Evening electric light & sleep

(0:09:42) Daylight & sleep

(0:15:47) Seasonal effects of daylight

(0:20:33) Can higher light intensities during daytime reduce negative effects of evening light?

(0:25:47) How to tackle the lack of daylight as a society?

(0:36:00) Take-home message on daylight & health

(0:37:39) Christian’s career goals & future research

(0:41:15) Funny anecdotes

(0:47:18) Outro & Teaser to Part 2

Studies that Christian refers to: Evening administration of melatonin and bright light: Interactions on the EEG during sleep and wakefulness

https://doi.org/10.1046/j.1365-2869.1998.00106.x

Blue Blocker Glasses as a Countermeasure for Alerting Effects of Evening Light-Emitting Diode Screen Exposure in Male Teenagers

https://doi.org/10.1016/j.jadohealth.2014.08.002

Evaluating the Association between Artificial Light-at-Night Exposure and Breast and Prostate Cancer Risk in Spain (MCC-Spain Study)

https://doi.org/10.1289/EHP1837

Camping Study: “Circadian Entrainment to the Natural Light-Dark Cycle across Seasons and the Weekend”

10.1016/j.cub.2016.12.041

Effect of daylight LED on visual comfort, melatonin, mood, waking performance and sleep

https://doi.org/10.1177/1477153519828419

Positive Effect of Daylight Exposure on Nocturnal Urinary Melatonin Excretion in the Elderly: A Cross-Sectional Analysis of the HEIJO-KYO Study

https://doi.org/10.1210/jc.2012-1873

Effect of Bright Light and Melatonin on Cognitive and Noncognitive Function in Elderly Residents of Group Care Facilities: A Randomized Controlled Trial

https://doi.org/10.1001/jama.299.22.2642

Preprint article: “Sex and seasonal variations in melatonin suppression, and alerting response to light”

https://doi.org/10.1101/2024.10.18.619012

Light therapy in non-seasonal depression: An update meta-analysis

https://doi.org/10.1016/j.psychres.2020.113247

Pre-print article: “Afternoon to early evening bright light exposure reduces later melatonin production in adolescents”

https://doi.org/10.1101/2024.10.02.616112

Regular Caffeine Intake Delays REM Sleep Promotion and Attenuates Sleep Quality in Healthy Men

https://doi.org/10.1177/07487304211013995

Evidence that the Lunar Cycle Influences Human Sleep

10.1016/j.cub.2013.06.029

How to contact Christian Cajochen:

Email: Christian.Cajochen@upk.ch

Twitter: @ollen44

LinkeIn: https://www.linkedin.com/in/christian-cajochen-1435258/

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

- how the eyes change upon aging and how this may affect circadian rhythms

- how light at night possibly via impaired sleep can lead to higher appetite & cravings for unhealthy food

- why "Why should I change anything? I sleep well!" people should still reduce light at night to improve health

- seasonal changes in light and their potential influence on human physiology

Link to Samer’s episode on the Hubermanlab Podcast:

Dr. Samer Hattar: Timing Light, Food, & Exercise for Better Sleep, Energy & Mood | Huberman Lab #43

https://www.youtube.com/watch?v=oUu3f0ETMJQ

Papers that Samer and I refer to:

Extraocular Circadian Phototransduction in Humans (Campbell & Murphy 1998)

https://www.science.org/doi/10.1126/science.279.5349.396?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Absence of Circadian Phase Resetting in Response to Bright Light Behind the Knees (Wright & Czeisler 2002)

https://www.science.org/doi/full/10.1126/science.1071697

FAILURE OF EXTRAOCULAR LIGHT TO FACILITATE CIRCADIAN RHYTHM REENTRAINMENT IN HUMANS (Eastman et al. 2000)

https://www.tandfonline.com/doi/abs/10.1081/cbi-100102116?journalCode=icbi20

Regulation of Mammalian Circadian Behavior by Non-rod, Non-cone, Ocular Photoreceptors (Freedman et al. 1999)

https://www.science.org/doi/full/10.1126/science.284.5413.502

Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea (Buhr et al. 2015)

https://www.pnas.org/doi/abs/10.1073/pnas.1516259112

Opsins have also been found in adipocytes of humans and mice:

Subcutaneous white adipocytes express a light sensitive signaling pathway mediated via a melanopsin/TRPC channel axis (Ondrusova et al. 2017)

https://pubmed.ncbi.nlm.nih.gov/29180820/

Adaptive Thermogenesis in Mice Is Enhanced by Opsin 3-Dependent Adipocyte Light Sensing (Nayak et al. 2020)

https://pubmed.ncbi.nlm.nih.gov/31968245/

Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant (Izumo et al. 2014)

https://elifesciences.org/articles/04617

Retinal innervation tunes circuits that drive nonphotic entrainment to food (Fernandez et al. 2020)

https://www.nature.com/articles/s41586-020-2204-1

Metabolic consequences of sleep and sleep loss (van Cauter et al. 2008)

https://www.sciencedirect.com/science/article/pii/S1389945708700133

Relationship between Sleep and Hedonic Appetite in Shift Workers (Vidafar et al. 2020)

https://www.mdpi.com/2072-6643/12/9/2835

Increased Hunger, Food Cravings, Food Reward, and Portion Size Selection after Sleep Curtailment in Women Without Obesity (Yang et al. 2019)

https://www.mdpi.com/2072-6643/11/3/663

NIH researcher studying sleep deprivation: Kong Chen

https://www.niddk.nih.gov/about-niddk/staff-directory/biography/chen-kong

Moonstruck sleep: Synchronization of human sleep with the moon cycle under field conditions (Casiraghi et al. 2021)

https://www.science.org/doi/full/10.1126/sciadv.abe0465

A Circannual Clock Drives Expression of Genes Central for Seasonal Reproduction (de Miera et al. 2014)

https://www.sciencedirect.com/science/article/pii/S0960982214005491

Light can activate the human prefrontal cortex:

Luxotonic signals in human prefrontal cortex as a possible substrate for effects of light on mood and cognition (Sabbah et al. 2022)

https://www.pnas.org/doi/10.1073/pnas.2118192119

Samer Hattar on Social Media:

Twitter: @SamerHattar

NIH-Homepage: https://www.nimh.nih.gov/research/research-conducted-at-nimh/principal-investigators/samer-hattar

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 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

In this second part, Dr. Christian Benedict (Department of Pharmaceutical Biosciences, Research and Pharmacology at Uppsala University, Sweden) explains how our sleep changes with aging and upon different challenges of adult life. We discuss the so-called gold-standard method for measuring sleep (Polysomnography, PSG) and how modern wearable technologies perform compared to PSG. In this context, Christian evaluates the potential value of measuring heart rate variability (HRV) to assess sleep quality. He also emphasizes the health threat through obstructive sleep apnea (OSA) and how to use simple self-monitoring technologies to determine if you may be affected by OSA yourself. Lastly, we acknowledge poor sleep as a general health risk but also discuss limitations and problems that can arise from overstating this.

Chapters:

(0:00:12) Intro

(0:02:20) Aging and sleep

(0:11:10) Polysomnography (PSG)

(0:22:25) Sleep wearables & HRV

(0:27:07) Obstructive sleep apnea

(0:33:10) Limitations of wearables

(0:36:41) Sleep across chronotypes

(0:44:50) Poor sleep as a health risk?

(0:55:19) Outro

Studies that Christian refers to:

Meta-analysis (2004) PSG data over the lifespan

https://pubmed.ncbi.nlm.nih.gov/15586779/

Paper on app findings of almost a million people asked on “how long do you sleep?”

https://pubmed.ncbi.nlm.nih.gov/36509747/

Studies on PSG vs. some commercial wearables ?

https://jcsm.aasm.org/doi/10.5664/jcsm.7128

Sleep apnea: Spotlight article with Jesse Cooks and Jonathan Cedernaes

https://pubmed.ncbi.nlm.nih.gov/33180697/

Lancet Respiratory Medicine review, 425 million people suffer from moderate to severeobstructive sleep apnea

https://pubmed.ncbi.nlm.nih.gov/31300334/

Ad-hoc sleep apnea screening in patients admitted to the hospital, 80% are not aware of it

https://pubmed.ncbi.nlm.nih.gov/19186102/

Australian study using a measurement pillow to track sleep apnea

https://www.atsjournals.org/doi/full/10.1164/rccm.202107-1761OC

Christian’s work (2015) those who have over 40 years regular sleep problems have an increased risk for Alzheimer’s

https://pubmed.ncbi.nlm.nih.gov/25438949/

Studies comparing people with kids and without kids, those with kids live longer

https://jech.bmj.com/content/71/5/424

How to contact Christian Benedict:

Email: Christian.benedict@farmbio.uu.se

LinkedIn: https://www.linkedin.com/in/christian-benedict-a25b1615a/

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 years of 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.

Literature underlying practical recommendations:

Banking Sleep: Realization of Benefits During Subsequent Sleep Restriction and Recovery (Rupp et al. 2020)

https://academic.oup.com/sleep/article/32/3/311/3741695

Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (Garaulet et al. 2022)

https://doi.org/10.2337/dc21-1314

Effects of caffeine on human behavior (Smith 2022)

https://doi.org/10.1016/S0278-6915(02)00096-0

Blue-blockers reduce melatonin suppression:

Blue Blocker Glasses as a Countermeasure for Alerting Effects of Evening Light-Emitting Diode Screen Exposure in Male Teenagers (van der Lely et al. 2014)

https://www.jahonline.org/article/S1054-139X(14)00324-3/fulltext

Rods and cones also play a role for light suppression on melatonin etc.

S-cone contribution to the acute melatonin suppression response in humans (Brown et al. 2021)

https://onlinelibrary.wiley.com/doi/full/10.1111/jpi.12719

Circadian Photoentrainment in Mice and Humans (Foster et al. 2020)

https://www.mdpi.com/2079-7737/9/7/180

Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms (Saner et al. 2021)

https://doi.org/10.1016/j.molmet.2020.101110

Prior Exercise Lowers Blood Pressure During Simulated Night-Work With Different Meal Schedules (Fullick et al. 2009)

https://pubmed.ncbi.nlm.nih.gov/19556971/

Impact of the human circadian system, exercise, and their interaction on cardiovascular function (Scheer et al. 2010)

https://www.pnas.org/doi/full/10.1073/pnas.1006749107

Timing of Moderate-to-Vigorous Physical Activity Is Associated with Improvements in Glycemic Control in Type 2 Diabetes in the Look AHEAD Study (Qian et al. 2022)

https://doi.org/10.2337/db22-537-P

Heart attacks are more common in the morning:

Circadian Variation of Ambulatory Myocardial Ischemia: Triggering by Daily Activities and Evidence for an Endogenous Circadian Component (Krantz et al. 1996)

https://doi.org/10.1161/01.CIR.93.7.1364

How to contact Frank Scheer:

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

Email: FSCHEER@BWH.HARVARD.EDU

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

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

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. In this first part, 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.

Link to Samer’s episode on the Hubermanlab Podcast:

Dr. Samer Hattar: Timing Light, Food, & Exercise for Better Sleep, Energy & Mood | Huberman Lab #43

https://www.youtube.com/watch?v=oUu3f0ETMJQ

Papers that Samer and I refer to:

Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus (Damiola et al. 2000)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC317100/

External light activates hair follicle stem cells through eyes via an ipRGC–SCN–sympathetic neural pathway (Fan et al. 2018)

https://www.pnas.org/doi/abs/10.1073/pnas.1719548115

The effects of extended photoperiod and warmth on hair growth in ponies and horses at different times of year (O’Brien et al. 2020)

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227115

The influence of bright and dim light on substrate metabolism, energy expenditure and thermoregulation in insulin-resistant individuals depends on time of day (Harmsen et al. 2022)

https://doi.org/10.1007/s00125-021-05643-9

Diurnal Blood Pressure Variations Are Associated with Changes in Distal–Proximal Skin Temperature Gradient (Kräuchi et al. 2012)

https://www.tandfonline.com/doi/full/10.3109/07420528.2012.719961

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

https://academic.oup.com/jcem/article/90/3/1311/2836588

Brain regions that receive light information, 53 brain regions are responsive in nocturnal mice:

Feature Detection by Retinal Ganglion Cells (Kerschensteiner 2022)

https://cpb-us-w2.wpmucdn.com/sites.wustl.edu/dist/d/1277/files/2022/04/KerschensteinerD-AnnuRevVisSci-2022.pdf

Entrainment of the Human Circadian Clock to the Natural Light-Dark Cycle (Wright et al. 2013)

https://www.sciencedirect.com/science/article/pii/S0960982213007641?via%3Dihub

Depressed Patients Hospitalized in Southeast-Facing Rooms Are Discharged Earlier than Patients in Northwest-Facing Rooms (Gbyl et al. 2016)

https://www.karger.com/Article/FullText/477249

Divergent outer retinal circuits drive image and non-image visual behaviors (Beier et al. 2022)

https://www.sciencedirect.com/science/article/pii/S2211124722007926

Red light can change the state of the melanopsin photo pigment:

Melanopsin Tristability for Sustained and Broadband Phototransduction (Emanuel & Do 2015) https://www.sciencedirect.com/science/article/pii/S0896627315001002

Samer Hattar on Social Media:

Twitter: @SamerHattar

NIH-Homepage: https://www.nimh.nih.gov/research/research-conducted-at-nimh/principal-investigators/samer-hattar

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.

Main paper that we discuss:

Physiological and Molecular Dissection of Daily Variance in Exercise Capacity

https://doi.org/10.1016/j.cmet.2019.03.012

Other papers that we refer to in our discussion:

Afternoon exercise is more efficacious than morning exercise at improving blood glucose levels in individuals with type 2 diabetes: a randomised crossover trial (Savikj et al. 2019)

https://link.springer.com/article/10.1007/s00125-018-4767-z

A circadian gene expression atlas in mammals: Implications for biology and medicine (Zhang et al. 2014)

https://doi.org/10.1073/pnas.1408886111

CRY1/2 Selectively Repress PPARδ and Limit Exercise Capacity (Jordan et al. 2017)

https://doi.org/10.1016/j.cmet.2017.06.002

Clock proteins and training modify exercise capacity in a daytime-dependent manner (Adamovich et al. 2021)

https://doi.org/10.1073/pnas.2101115118

PER2 controls lipid metabolism by direct regulation of PPARγ (Grimaldi et al. 2010)

https://doi.org/10.1016/j.cmet.2010.10.005

The Circadian Protein Period2 Suppresses mTORC1 Activity via Recruiting Tsc1 to mTORC1 Complex (Wu et al. 2019)

https://doi.org/10.1016/j.cmet.2018.11.006

AMPK Activation via Modulation of De Novo Purine Biosynthesis with an Inhibitor of ATIC Homodimerization (Asby et al. 2015)

https://doi.org/10.1016/j.chembiol.2015.06.008

Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain (Horowitz et al. 2020)

https://doi.org/10.1126/science.aaw2622

Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and zeitgeber activity of training in mouse muscle (Maier et al. 2022)

https://doi.org/10.1113/JP281535

Atlas of exercise metabolism reveals time-dependent signatures of metabolic homeostasis (Kräuchi et al. 1999)

https://doi.org/10.1016/j.cmet.2021.12.016

Saar's and Gad Asher's review on circadian control in mitochondria:

Circadian control of mitochondrial dynamics and functions (Ezagouri & Asher 2018)

https://doi.org/10.1016/j.cophys.2018.05.008

References to the marathon mice (Ronald Evans):

https://www.hhmi.org/news/researchers-identify-drugs-enhance-exercise-endurance

https://www.cell.com/fulltext/S0092-8674(08)00838-6

Saar Ezagourio on Social Media:

Twitter: @SaarEzagouri_RD

Email: saare@weizmann.ac.il

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.

Correction by Frank Scheer:

"The Medical Chronobiology Program was already founded in 2005, not 2015."

Main papers that we discuss in depth:

Daytime eating prevents internal circadian misalignment and glucose intolerance in night work (Chellappa et al. 2021)

https://www.science.org/doi/10.1126/sciadv.abg9910

Late isocaloric eating increases hunger, decreases energy expenditure, and modifies metabolic pathways in adults with overweight and obesity (Vujovic et al. 2022)

https://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(22)00397-7

Additional papers that Frank and I refer to:

Adaptation of the circadian rhythm of 6-sulphatoxymelatonin to a shift schedule of seven nights followed by seven days in offshore oil installation workers (Gibbs et al. 2002)

https://doi.org/10.1016/S0304-3940(02)00247-1

Adaptation of the melatonin rhythm in human subjects following night-shift work in Antarctica (Midwinter & Arendt 1991)

https://pubmed.ncbi.nlm.nih.gov/2027519/

Energy Expenditure and Changes in Body Composition During Submarine Deployment—An Observational Study “DasBoost 2-2017” (Rietjens et al. 2020)

https://www.mdpi.com/2072-6643/12/1/226

The Relationship between Working Night Shifts and Depression among Nurses: A Systematic Review and Meta-Analysis (Okechukwu et al. 2023)

https://pubmed.ncbi.nlm.nih.gov/37046864/

Circadian misalignment increases mood vulnerability in simulated shift work (Chellappa et al. 2020)

https://www.nature.com/articles/s41598-020-75245-9

Proof-of-principle demonstration of endogenous circadian system and circadian misalignment effects on human oral microbiota (Chellappa et al. 2022)

https://pubmed.ncbi.nlm.nih.gov/34861073/

Review articles on shift work and health risks:

Impact of circadian disruption on glucose metabolism: implications for type 2 diabetes (Mason et al. 2020)

https://pubmed.ncbi.nlm.nih.gov/31915891/

Impact of Circadian Disruption on Cardiovascular Function and Disease (Chellappa et al. 2019)

https://pubmed.ncbi.nlm.nih.gov/31427142/

Health consequences of circadian disruption (Sletten et al. 2020)

https://academic.oup.com/sleep/article/43/1/zsz194/5699236?login=true

Effects of circadian disruption on the cardiometabolic system (Rüger & Scheer 2009)

https://link.springer.com/article/10.1007/s11154-009-9122-8

The endogenous circadian system worsens asthma at night independent of sleep and other daily behavioral or environmental cycles (Scheer et al. 2020)

https://www.pnas.org/doi/abs/10.1073/pnas.2018486118

The two-process model of sleep regulation: Beginnings and outlook (Borbely 2022)

https://onlinelibrary.wiley.com/doi/full/10.1111/jsr.13598

Controlling for sleep as a factor in the negative effects of shift work, circadian misalignment is above and beyond sleep-disruptive effects:

Circadian Misalignment Augments Markers of Insulin Resistance and Inflammation, Independently of Sleep Loss (Leproult et al. 2014)

https://diabetesjournals.org/diabetes/article/63/6/1860/34298/Circadian-Misalignment-Augments-Markers-of-Insulin

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans (Morris et al. 2015)

https://www.pnas.org/doi/abs/10.1073/pnas.1418955112

Adverse metabolic and cardiovascular consequences of circadian misalignment (Scheer et al. 2009)

https://www.pnas.org/doi/abs/10.1073/pnas.0808180106

Shift work studies in mice by Carolina Escobar:

Food Intake during the Normal Activity Phase Prevents Obesity and Circadian Desynchrony in a Rat Model of Night Work (Salgado-Delgado et al. 2010)

https://academic.oup.com/endo/article/151/3/1019/2456529

Shift Work or Food Intake during the Rest Phase Promotes Metabolic Disruption and Desynchrony of Liver Genes in Male Rats (Salgado-Delgado et al. 2013)

https://doi.org/10.1371/journal.pone.0060052

Timing of food intake predicts weight loss effectiveness (Garaulet et al. 2013)

https://www.nature.com/articles/ijo2012229

How to contact Frank Scheer:

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

Email: FSCHEER@BWH.HARVARD.EDU

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.

Main paper that we discuss:

Effectiveness of Early Time-Restricted Eating for Weight Loss, Fat Loss, and Cardiometabolic Health in Adults With Obesity (Jamshed et al. 2022)

https://pubmed.ncbi.nlm.nih.gov/35939311/

Other papers we refer to:

Early Time-Restricted Feeding Reduces Appetite and Increases Fat Oxidation But Does Not Affect Energy Expenditure in Humans (Ravussin et al. 2019)

https://doi.org/10.1002/oby.22518

3month vs 1year diet intervention, participants falling off the wagon after a year in contrast to benefits after 3 months (Courtney could not recall the exact article)

Recent chronotype paper from Courtney, in terms of sticking to early time-restricted eating (work in progress from Courtney)

Calorie Restriction with or without Time-Restricted Eating in Weight Loss (Liu et al. 2022)

https://www.nejm.org/doi/full/10.1056/NEJMoa2114833

Beneficial Effects of Time-Restricted Eating on Metabolic Diseases: A Systemic Review and Meta-Analysis (Moon et al. 2020)

https://www.mdpi.com/2072-6643/12/5/1267

TRF effects on satiety hormones especially in the evening:

Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes (Sutton et al. 2018)

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30253-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413118302535%3Fshowall%3Dtrue

TRF might increase diet-induced thermogenesis and calories stored in stool samples (Courtney could not recall the exact article)

Late isocaloric eating increases hunger, decreases energy expenditure, and modifies metabolic pathways in adults with overweight and obesity (Vujovic et al. 2022)

https://doi.org/10.1016/j.cmet.2022.09.007

Daytime eating prevents internal circadian misalignment and glucose intolerance in night work (Chellappa et al. 2021)

https://www.science.org/doi/full/10.1126/sciadv.abg9910

Epidemiological studies avoiding calories in the 2 hours before bedtime (Courtney could not recall the exact article)

How to contact Courtney Peterson:

Email: cpeterso@uab.edu

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.

Main paper that we discuss: Timing of daily calorie loading affects appetite and hunger responses without changes in energy metabolism in healthy subjects with obesity (Ruddick-Collins et al. 2022) https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00344-8

Additional papers that Alex and I refer to:

Timing of food intake predicts weight loss effectiveness (Garaulet et al. 2013)

https://www.nature.com/articles/ijo2012229

High Caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women (Jakubowicz et al. 2013)

https://onlinelibrary.wiley.com/doi/10.1002/oby.20460

Feeding rodents during light hours makes them obese compared to feeding them during the dark period:

Circadian Timing of Food Intake Contributes to Weight Gain (Arble et al. 2009)

https://onlinelibrary.wiley.com/doi/full/10.1038/oby.2009.264

Circadian component on the thermic effect of food:

Circadian Rhythms in Resting Metabolic Rate Account for Apparent Daily Rhythms in the Thermic Effect of Food (Ruddick-Collins)

https://doi.org/10.1210/clinem/dgab654

Late isocaloric eating increases hunger, decreases energy expenditure, and modifies metabolic pathways in adults with overweight and obesity (Vujovic et al. 2022)

https://doi.org/10.1016/j.cmet.2022.09.007

Impact of Meal Timing and Chronotype on Food Reward and Appetite Control in Young Adults (Beaulieu et al. 2020)

https://www.mdpi.com/2072-6643/12/5/1506

James Bett's definition of breakfast is “within 2-3hours after waking”:

Is breakfast the most important meal of the day? (Betts et al. 2016)

https://www.cambridge.org/core/journals/proceedings-of-the-nutrition-society/article/is-breakfast-the-most-important-meal-of-the-day/74DC8BF20CAF1D7D5E75CD46A35451F8

German bunker studies:

Human circadian rhythms: a multioscillatory system. (Aschoff & Wever 1976)

https://europepmc.org/article/med/786739

How to contact Alex Johnstone:

Twitter: @Dr_A_Johnstone

Email: alex.johnstone@abdn.ac.uk

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.

Main paper that I discuss:

The influence of bright and dim light on substrate metabolism, energy expenditure and thermoregulation in insulin-resistant individuals depends on time of day

https://doi.org/10.1007/s00125-021-05643-9

Other papers and resources that I refer to :

The MyLux app for smartphones is to my surprise not available anymore when I checked the appstore, but my explanations on its use and limitations would apply to any other lux-measuring app as they all measure lux via the smartphone-integrated camera.

Dr. Samer Hattar: Timing Light, Food, & Exercise for Better Sleep, Energy & Mood | Huberman Lab #43

https://www.youtube.com/watch?v=oUu3f0ETMJQ&ab_channel=AndrewHuberman

High sensitivity and interindividual variability in the response of the human circadian system to evening light

https://www.pnas.org/doi/full/10.1073/pnas.1901824116

The effects of prior light history on the suppression of melatonin by light in humans

https://onlinelibrary.wiley.com/doi/epdf/10.1034/j.1600-079X.2002.01885.x

Acute Effects of Morning Light on Plasma Glucose and Triglycerides in Healthy Men and Men with Type 2 Diabetes

https://doi.org/10.1177/0748730417693480

Melatonin Effects on Glucose Metabolism: Time To Unlock the Controversy

https://doi.org/10.1016/j.tem.2019.11.011

Functional link between distal vasodilation and sleep-onset latency?

https://doi.org/10.1152/ajpregu.2000.278.3.R741

Diurnal Blood Pressure Variations Are Associated with Changes in Distal–Proximal Skin Temperature Gradient

https://doi.org/10.3109/07420528.2012.719961

Effects of dim or bright-light exposure during the daytime on human gastrointestinal activity.

https://doi.org/10.1081/CBI-120017688

Increase in parasympathetic nerve activity during the nighttime following bright light exposure during the daytime.

https://doi.org/10.1076/brhm.34.3.233.18809

Salivary secretion under the influence of bright/dim light exposure in the morning

https://doi.org/10.1076/brhm.33.2.129.1316

Dr. Christian Benedict (Senior Lecturer & Associate Professor at the Department of Pharmaceutical Biosciences, Research and Pharmacology at Uppsala University, Sweden) talks about how to study sleep and its relevance for our overall health. In this first part, Christian introduces us to different definitions of sleep. Together, we try to decipher the concept of sleep quality or in other words how to judge if somebody had a good night’s sleep or not. Christian also summarizes the research around the optimal duration of sleep and discusses the relevanceof spending time in different sleep stages.

Chapters:

(0:00:12) Intro

(0:03:41) Christian Benedict’s career path

(0:13:06) What is sleep?

(0:24:09) Sleep stages & sleep quality

(0:34:06) Sleep quantity/duration

(0:42:08) Outro & Teaser to Part 2

Studies that Christian refers to:

Aversive tobacco smoke during non-REM sleep

https://pubmed.ncbi.nlm.nih.gov/25392505/

Epileptic patients and sleep deprivation

https://pubmed.ncbi.nlm.nih.gov/29106402/

Correlations between time in different sleep stages and daytime alertness are not that good, contradictory evidence

https://pubmed.ncbi.nlm.nih.gov/10678518/

Epworthsleepiness scale and sleep stages are not well correlated

https://pubmed.ncbi.nlm.nih.gov/19110886/

People struggling with sleep do not necessarily differ in PSG-derived sleep stage outcomes from normally sleeping people

https://pubmed.ncbi.nlm.nih.gov/29402512/

Peer feedback can impact your retrospective judgement of your last night of sleep

https://pubmed.ncbi.nlm.nih.gov/24417326/

https://pubmed.ncbi.nlm.nih.gov/33204201/

American Society for Sleep Medicine, 7-9 hours, probably 6 and 10 hours are also fine

https://www.thensf.org/wp-content/uploads/2020/10/NSF-SleepDurationTiming_Background-1200x1312-1.jpg

Shorter or longer than these 6-10 hours is mostly associated with poor health outcomes

https://pubmed.ncbi.nlm.nih.gov/11825133/

Christian’s work on interindividual responses in brain health outcomes to sleep loss

https://pubmed.ncbi.nlm.nih.gov/36088460/

Studies showing that people who think they cope well with sleep loss are actually not doing well

https://pubmed.ncbi.nlm.nih.gov/29383809/

How to contact Christian Benedict:

Email: Christian.benedict@farmbio.uu.se

LinkedIn: https://www.linkedin.com/in/christian-benedict-a25b1615a/

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.

Main paper that we discuss:

Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms

https://www.sciencedirect.com/science/article/pii/S2212877820301848#!

Other papers that we refer to in our discussion:

Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects (Schrauwen-Hinderling et al. 2007)

https://link.springer.com/article/10.1007/s00125-006-0475-1

Restoration of Muscle Mitochondrial Function and Metabolic Flexibility in Type 2 Diabetes by Exercise Training Is Paralleled by Increased Myocellular Fat Storage and Improved Insulin Sensitivity (Meex et al. 2010)

https://diabetesjournals.org/diabetes/article/59/3/572/13809/Restoration-of-Muscle-Mitochondrial-Function-and

Demonstration of a day-night rhythm in human skeletal muscle oxidative capacity (van Moorsel et al. 2016)

https://www.sciencedirect.com/science/article/pii/S2212877816300758?via%3Dihub

Day-night rhythm of skeletal muscle metabolism is disturbed in older, metabolically compromised individuals (Wefers et al. 2020) https://www.sciencedirect.com/science/article/pii/S2212877820301241?via%3Dihub

Impact of sleep debt on metabolic and endocrine function (Spiegel et al. 1999) https://www.sciencedirect.com/science/article/pii/S0140673699013768?casa_token=z2nO4CK4FcIAAAAA:EJmoSOZyEzwZSgiFhrHxBfli28M_qik3EDqa23wP5WWy0w32lq3Svua-BoB9IuUnMeqAI5nx_Uw

Effects of sleep deprivation on the activity of selected metabolic enzymes in skeletal muscle ( Vondra et al. 1981)

https://link.springer.com/article/10.1007/BF00422481

Even with recovery sleep, insulin sensitivity is still impaired:

Ad libitum Weekend Recovery Sleep Fails to Prevent Metabolic Dysregulation during a Repeating Pattern of Insufficient Sleep and Weekend Recovery Sleep (Depner et al. 2019)

https://www.sciencedirect.com/science/article/pii/S0960982219300983

Afternoon exercise is more efficacious than morning exercise at improving blood glucose levels in individuals with type 2 diabetes: a randomised crossover trial (Savikj et al. 2019)

https://link.springer.com/article/10.1007/s00125-018-4767-z

Distal skin temperature changes in response to light exposure:

High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light (Cajochen et al. 2015)

https://academic.oup.com/jcem/article/90/3/1311/2836588

Frieder’s recent paper on light exposure and diurnal rhythms in skin temperature:

The influence of bright and dim light on substrate metabolism, energy expenditure and thermoregulation in insulin-resistant individuals depends on time of day (Harmsen et al. 2022)

https://link.springer.com/article/10.1007/s00125-021-05643-9

Diurnal Blood Pressure Variations Are Associated with Changes in Distal–Proximal Skin Temperature Gradient (Kräuchi et al. 2012)

https://www.tandfonline.com/doi/full/10.3109/07420528.2012.719961

Warm feet promote the onset of sleep (Kräuchi et al. 1999)

https://www.nature.com/articles/43366

Nick's Review with Brad Schoenfield:

The effects of time of day-specific resistance training on adaptations in skeletal muscle hypertrophy and muscle strength: A systematic review and meta-analysis (Grgic et al. 2019)

https://www.tandfonline.com/doi/full/10.1080/07420528.2019.1567524?casa_token=Nceg32sjid4AAAAA%3AkS5mCHz_i1d4-0Ihk2OnGw1dw5A7M1oQiYZvYR20wQTU7uy6O6subnF0ScBOEOpW_g8r5UznGEvyuA

Nick Saner on Social Media:

Twitter: @NickSaner

Email: nicholas.saner@baker.edu.au

In collaboration with the organizers of the 18th Congress of the European Biological Rhythms Society (EBRS) (taking place in Lübeck in Northern Germany from the 24th to 28th of August 2025), three congress speakers are interviewed to talk about their research. As the first spotlight, Prof. Michael Hastings (MRC Laboratory of Molecular Biology, Cambridge) talks about his research journey from circatidal rhythms in marine organisms to circadian and circaannual rhythms in mammals. Our main focus is on the neurochemistry within the central clock of the suprachiasmatic nucleus (SCN) enabling it to tell time. We discuss the most relevant factors that support the SCN in telling time, and what means the SCN has to synchronize other clocks within our body. With respect to melatonin, we discuss its role in sleep versus informing our body about the current season. We also talk about supplementing melatonin for specific populations. Lastly, Michael shares memories from attending previous EBRS congresses and why you should consider joining it this year.

Chapters:

(00:00:39) Introducing the EBRS 2025 spotlights

(00:03:51) Michael Hastings

(00:07:17) Circatidal rhythms

(00:14:38) The central clock or SCN

(00:24:47) Different zeitgebers

(00:35:17) Melatonin

(00:46:14) Melatonin as a sleeping aid

(00:51:38) EBRS congress experience

(00:58:22) Career advice

(01:10:02) Funny anecdote

(01:13:54) Outro

Studies that Michael refers to:

Reviews on circatidal rhythms

https://doi.org/10.1016/j.cub.2008.06.041

https://doi.org/10.1016/j.tig.2024.01.006

Prevalence of mutations in clock genes to make the period length shorter or longer than approx. 24 hours, rare familial sleep disorders

https://doi.org/10.1038/s41386-019-0476-7

Mice mutations support that the same enzymes are involved as in the human sleep disorders

https://www.nature.com/articles/s41583-018-0026-z

Period genes in the SCN are activated by light

https://doi.org/10.1016/S0092-8674(00)80494-8

Caffeine can phase shift the circadian clock

https://doi.org/10.1126/scitranslmed.aac5125

Manipulation of NPY and serotonin can shift the SCN clock

https://doi.org/10.1152/ajpregu.00320.2022

Human cortisol levels increase before awakening in anticipation of wake

https://doi.org/10.1677/JOE-07-0378

Temperature in the physiological range can act as a zeitgeber to entrain peripheral clocks

https://doi.org/10.1016/S0960-9822(02)01145-4

When interfering with neuropeptide levels within the SCN, you can entrain the SCN with temperature cycles

https://doi.org/10.1126/science.1195262

High levels of estradiol make the SCN run faster

https://doi.org/10.1126/science.557840

Melatonin is a transplacental zeitgeber

https://pubmed.ncbi.nlm.nih.gov/3780553/

https://doi.org/10.1177/074873049701200603

Martha Gillette and others applied melatonin to brain slides containing the SCN, showing that this could shift the SCN clock, the sensitivity of the SCN to this melatonin effect was found to occur during daytime (when melatonin is not released naturally)

https://link.springer.com/article/10.1007/s00441-002-0576-1

GWAS papers: variance of melatonin receptor are related to the type 2 diabetes andmetabolic disorders

https://www.nature.com/articles/ng.277

https://www.nature.com/articles/s41574-018-0130-1

Contacting Michael Hastings:

Homepage: https://www2.mrc-lmb.cam.ac.uk/group-leaders/h-to-m/michael-hastings/

Email: ⁠mha@mrc-lmb.cam.ac.uk⁠

EBRS homepage:

https://ebrs-online.org

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

Russell Foster's recently published book: "Lifetime"

Papers/books that Russell refers to:

"Spectral Sensitivity Tuning in the Deep-Sea" (Douglas et al. 2003)

https://link.springer.com/chapter/10.1007/978-0-387-22628-6_17

J. N. Lythgoe's book: "The Ecology of Vision"

"Sensitivity and integration in a visual pathway for circadian entrainment in the hamster (Mesocricetus auratus)" (Nelson & Takahashi 1991)

https://doi.org/10.1113/jphysiol.1991.sp018660

"Phase-dependent shift of free-running human circadian rhythms in response to a single bright pulse" (Honma et al. 1987)

https://link.springer.com/article/10.1007/BF01945525

"Phototransduction by Retinal Ganglion Cells That Set the Circadian Clock" (Berson et al. 2002)

https://doi.org/10.1126/science.1067262

Russell's group to demonstrate the existence of retinal ganglion cells in mice:

"Melanopsin retinal ganglion cells and the maintenance of circadian and pupillary responses to light in aged rodless/coneless (rd/rd cl) mice" (Semo et al. 2003)

https://doi.org/10.1046/j.1460-9568.2003.02616.x

Retinal ganglion cells in the macaque:

"Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN" (Dacey et al. 2005)

https://www.nature.com/articles/nature03387

Skin of frogs, melanophores --> melanopsin

"Melanopsin: An opsin in melanophores, brain, and eye" (Provencio et al. 1998)

https://pubmed.ncbi.nlm.nih.gov/9419377/

VA opsin only in fish, not in mammals

"A novel and ancient vertebrate opsin" (Soni & Foster 1998)

https://doi.org/10.1016/S0014-5793(97)00287-1

Samer Hattar’s work: projections to the hypothalamus from melanopsin

"Central projections of melanopsin-expressing retinal ganglion cells in the mouse" (Hattar et al. 2006)

https://doi.org/10.1002/cne.20970

"Circadian photoreception in the retinally degenerate mouse (rd/rd)" (Foster et al. 1991)

https://link.springer.com/article/10.1007/BF00198171

"Neural Reprogramming in Retinal Degeneration" (Marc et al. 2007)

https://doi.org/10.1167/iovs.07-0032

"Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections" (Abrahamson & Moore 2001)

https://doi.org/10.1016/S0006-8993(01)02890-6

Martin Ralph's tau mutant hamster, restore rhythms to the period of the donor:

"Transplanted suprachiasmatic nucleus determines circadian period" (Ralph et al. 1990)

https://www.science.org/doi/abs/10.1126/science.2305266

Peripheral clocks concept shown by Uli Schibler's group in fibroblasts:

"Resetting of Circadian Time in Peripheral Tissues by Glucocorticoid Signaling" (Balsalobre et al. 2000)

https://www.science.org/doi/10.1126/science.289.5488.2344

Josephine Arendt melatonin pioneer:

"Melatonin as a chronobiotic" (Arendt & Skene 2005)

https://doi.org/10.1016/j.smrv.2004.05.002

Contradictory evidence for the use of melatonin to facilitate the onset of sleep

Example meta-analysis article: "Effects of exogenous melatonin on sleep: a meta-analysis" (Brzezinski et al. 2005)

https://doi.org/10.1016/j.smrv.2004.06.004

Patients on beta-blockers produce less melatonin:

"Influence of beta-blockers on melatonin release" (Stoschitzky et al. 1999)

https://link.springer.com/article/10.1007/s002280050604

How to contact Russell Foster:

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

After discussing in the first part how caloric restriction can extend lifespan, Dr. Victoria Acosta-Rodriguez (Leader of the Circadian Biology of Aging Unit at the National Institute on Aging (NIA), USA) talks in the second part about her recent study showing that eating these reduced calories always at a certain time of day extends the lifespan of mice even further. Beyond longevity, her study reveals that enhanced health benefits are achieved when feeding versus fasting times are aligned with the natural active and rest phase of mice as dictated by circadian clocks. In the end, we discuss the feasibility of long-term caloric restriction for humans and if similar health benefits could be expected in humans.

Chapters:

(00:00:45) Recap Part 1

(00:01:28) Part 2 topics

(00:02:09) Interview start

(00:03:28) Explaining the study design

(00:10:01) What kind of food did mice eat and why?

(00:13:56) Body weight changes over the lifespan

(00:15:58) Relevance of fasting duration

(00:19:45) A calorie is a calorie?

(00:22:47) The longest-lived mice

(00:25:49) Cause of death for 300 mice

(00:29:46) Physical activity as a survival predictor

(00:31:56) Body composition & metabolic health

(00:35:55) 48-hour liver samples

(00:47:18) Study limitations

(00:51:59) Monkey studies

(00:55:16) Feasibility of caloric restriction for humans

(00:59:21) Personal perspective

(01:09:00) 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:

Rhesus Monkeys - Caloric restriction & Lifespan

Mattison, J. A. et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489, 318–321 (2012).

Colman, R. J. et al. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat. Commun. 5, 3557 (2014).

Mattison, J. A. et al. Caloric restriction improves health and survival of rhesus monkeys. Nat. Commun. 8, 14063 (2017).

Humans -TRF

Sutton, E.F., Beyl, R., Early, K.S., Cefalu, W.T., Ravussin, E., and Peterson, C.M. (2018). Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Cell Metab 27, 1212-1221 e1213. 10.1016/j.cmet.2018.04.010.

Humans - CALERIE study

Martin, C. K. et al. Effect of calorie restriction on mood, quality of life, sleep, and sexual function in healthy nonobese adults: the CALERIE 2 randomized clinical trial. JAMA Intern. Med. 176, 743–752 (2016).

Das, S. K. et al. Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-year randomized controlled trial of calorie restriction in nonobese humans. Am. J. Clin. Nutr. 105, 913–927 (2017).

Mice – NIA Intervention Testing Program

https://www.nia.nih.gov/research/dab/interventions-testing-program-itp

 Francesca Macchiarini, Richard A. Miller, Randy Strong, Nadia Rosenthal, David E. Harrison,

Chapter 10 - NIA Interventions Testing Program: A collaborative approach for investigating interventions to promote healthy aging, In Handbooks of Aging, Handbook of the Biology of Aging (Ninth Edition), Academic Press, 2021, Pages 219-235, ISBN 9780128159620,

https://doi.org/10.1016/B978-0-12-815962-0.00010-X

Contact: Dr. Victoria Acosta-Rodriguez

Email: victoria.acosta-rodriguez@nih.gov

Twitter/X: @VickyAcostaR

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

Papers that I refer to:

Muscle cramps induce muscle hypertrophy:

"Electrically induced muscle cramps induce hypertrophy of calf muscles in healthy adults"

http://www.ismni.org/jmni/pdf/60/14BEHRINGER.pdf

Electric muscle stimulation to treat muscle cramps:

"Neuromuscular Electrical Stimulation Reduces Leg Cramps in Patients With Lumbar Degenerative Disorders: A Randomized Placebo-Controlled Trial"

https://www.sciencedirect.com/science/article/pii/S1094715921069117?via%3Dihub

Blood-flow-restriction training in the context of total knee replacement surgery:

"Soft-tissue damage during total knee arthroplasty: Focus on tourniquet-induced metabolic and ionic muscle impairment"

https://www.sciencedirect.com/science/article/pii/S0972978X17300442?via%3Dihub

Study showing that simulating night-shift work in young men for 3.5 days induces insulin resistance:

"Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle"

https://www.pnas.org/content/115/30/7789

Check out research from:

Prof. Janet Taylor - https://www.ecu.edu.au/schools/medical-and-health-sciences/our-staff/profiles/professors/professor-janet-taylor

Prof. Anthony Blazevich - https://www.ecu.edu.au/schools/medical-and-health-sciences/our-staff/profiles/professors/professor-anthony-blazevich

Other podcasts that I recommend:

Sigma Nutrition by Danny Lennon - https://sigmanutrition.com

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

As part of the Daylight Awareness Week (28th of October - 2nd of November 2024), Prof. Christian Cajochen (Head of the Centre for Chronobiology at the University of Basel in Switzerland) talks about the impact of daylight on our health, with a special focus on sleep. In the first part, we talk about the importance of light for the circadian timing system within our bodies, with melatonin playing an important role. Christian explains why light can have very different effects on our health depending on the time of day of light exposure, and highlights the most important time to see daylight. Christian points out the benefits of daylight particularly for older people. We also critically discuss how difficult it is to study the health effects of daylight without any confounding from other "side-benefits" outdoors. And lastly, we discuss the effects of light on our cardiovascular system (like heart rate and blood pressure) as well as alertness.

More information about the Daylight Awareness Week: https://daylight.academy/daylight-awareness-week-2024/

Chapters:

(0:00:12) Intro & Daylight Awareness Week

(0:02:10) Topics of this episode series

(0:03:33) Introducing Christian Cajochen

(0:08:21) Daylight vs. electric light

(0:13:28) Circadian clocks & melatonin

(0:20:31) Wavelength dependency

(0:23:13) Timing of light matters

(0:30:43) How to study health effects of daylight without confounders?

(0:38:32) Light & Cardiovascular health

(0:45:31) Warm feet to promote sleep

(0:52:14) Light & Blood pressure

(0:56:11) Outro & Teaser to Part 2

Studies that Christian refers to:

The aging clock: circadian rhythms and later life

https://doi.org/10.1172/JCI90328

A Phase Response Curve to Single Bright Light Pulses in Human Subjects

https://doi.org/10.1113/jphysiol.2003.040477

Positive Effect of Daylight Exposure on Nocturnal Urinary Melatonin Excretion in the Elderly: A Cross-Sectional Analysis of the HEIJO-KYO Study

https://doi.org/10.1210/jc.2012-1873

The biological clock tunes the organs of the body: timing by hormones and the autonomic nervous system

https://doi.org/10.1677/joe.0.1770017

Light activates the adrenal gland: Timing of gene expression and glucocorticoid release

10.1016/j.cmet.2005.09.009

Warm feet promote the rapid onset of sleep

https://www.nature.com/articles/43366

Functional link between distal vasodilation and sleep-onset latency?

https://doi.org/10.1152/ajpregu.2000.278.3.R741

Changing color and intensity of LED lighting across the day impacts on circadian melatonin rhythms and sleep in healthy men

https://doi.org/10.1111/jpi.12714

Circadian mechanisms of 24-hour blood pressure regulation and patterning

https://doi.org/10.1016/j.smrv.2016.02.003

Alerting effects of light

https://doi.org/10.1016/j.smrv.2007.07.009

How to contact Christian Cajochen:

Email: Christian.Cajochen@upk.ch

Twitter: @ollen44

LinkeIn: https://www.linkedin.com/in/christian-cajochen-1435258/

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.

Main papers that we discuss:

Postexercise cooling impairs muscle protein synthesis rates in recreational athletes (Fuchs et al. 2019)

https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP278996

Hot-water immersion does not increase postprandial muscle protein synthesis rates during recovery from resistance-type exercise in healthy, young males (Fuchs et al. 2021) https://journals.physiology.org/doi/full/10.1152/japplphysiol.00836.2019

Additional papers that Cas and I refer to:

Review on the muscle protein synthesis approach:

The Muscle Protein Synthetic Response to Meal Ingestion Following Resistance-Type Exercise (Trommelen et al. 2019)

https://link.springer.com/article/10.1007/s40279-019-01053-5

Studies on lowering pain after exercise through the cold:

Cold water immersion and recovery from strenuous exercise: a meta-analysis (Leeder et al. 2019)

https://paulogentil.com/pdf/Cold%20water%20immersion%20and%20recovery%20from%20strenuous%20exercise%20-%20a%20meta-analysis.pdf

Cold to maintain workload in sets:

Water Immersion Recovery for Athletes: Effect on Exercise Performance and Practical Recommendations (Versey et al. 2013)

https://link.springer.com/article/10.1007/s40279-013-0063-8

Postexercise cold water immersion benefits are not greater than the placebo effect (Broatch et al. 2014)

https://pubmed.ncbi.nlm.nih.gov/24674975/

More long-term studies on cold water immersion on muscle mass and strength being lower (group from Australia):

Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training (Roberts et al. 2015)

https://pubmed.ncbi.nlm.nih.gov/26174323/

Previous study on muscle inflammation markers after cooling, but found no differences:

The effects of cold water immersion and active recovery on inflammation and cell stress responses in human skeletal muscle after resistance exercise (Peake et al. 2016)

https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP272881

Cold on the muscle clock in mice:

Time-of-Day Effects on Metabolic and Clock-Related Adjustments to Cold (Machado et al. 2018)

https://www.frontiersin.org/articles/10.3389/fendo.2018.00199/full

How to contact with Cas Fuchs:

Twitter: @27CJ

Email: cas.fuchs@maastrichtuniversity.nl