bims-ciryme 2021-07-25 papers

Semin Cell Dev Biol. 2021 Jul 16. pii: S1084-9521(21)00195-6. [Epub ahead of print]

Circadian NAD(P)(H) cycles in cell metabolism.

Daniel C Levine, Kathryn M Ramsey, Joseph Bass.

Intrinsic circadian clocks are present in all forms of photosensitive life, enabling daily anticipation of the light/dark cycle and separation of energy storage and utilization cycles on a 24-h timescale. The core mechanism underlying circadian rhythmicity involves a cell-autonomous transcription/translation feedback loop that in turn drives rhythmic organismal physiology. In mammals, genetic studies have established that the core clock plays an essential role in maintaining metabolic health through actions within both brain pacemaker neurons and peripheral tissues and that disruption of the clock contributes to disease. Peripheral clocks, in turn, can be entrained by metabolic cues. In this review, we focus on the role of the nucleotide NAD(P)(H) and NAD+-dependent sirtuin deacetylases as integrators of circadian and metabolic cycles, as well as the implications for this interrelationship in healthful aging.

Keywords: Aging; Circadian clock; Metabolism; Nicotinamide adenine dinucleotide (NAD(+)); Sirtuins

DOI: https://doi.org/10.1016/j.semcdb.2021.07.008

Genes Dev. 2021 Jul 22.

Protein phosphatase 4 controls circadian clock dynamics by modulating CLOCK/BMAL1 activity.

Sabrina Klemz, Thomas Wallach, Sandra Korge, Mechthild Rosing, Roman Klemz, Bert Maier, Nicholas C Fiorenza, Irem Kaymak, Anna K Fritzsche, Erik D Herzog, Ralf Stanewsky, Achim Kramer.

In all organisms with circadian clocks, post-translational modifications of clock proteins control the dynamics of circadian rhythms, with phosphorylation playing a dominant role. All major clock proteins are highly phosphorylated, and many kinases have been described to be responsible. In contrast, it is largely unclear whether and to what extent their counterparts, the phosphatases, play an equally crucial role. To investigate this, we performed a systematic RNAi screen in human cells and identified protein phosphatase 4 (PPP4) with its regulatory subunit PPP4R2 as critical components of the circadian system in both mammals and Drosophila Genetic depletion of PPP4 shortens the circadian period, whereas overexpression lengthens it. PPP4 inhibits CLOCK/BMAL1 transactivation activity by binding to BMAL1 and counteracting its phosphorylation. This leads to increased CLOCK/BMAL1 DNA occupancy and decreased transcriptional activity, which counteracts the "kamikaze" properties of CLOCK/BMAL1. Through this mechanism, PPP4 contributes to the critical delay of negative feedback by retarding PER/CRY/CK1δ-mediated inhibition of CLOCK/BMAL1.

Keywords: BMAL1; CLOCK; circadian clock; circadian rhythm; phosphorylation; protein phosphatase 4

DOI: https://doi.org/10.1101/gad.348622.121

Sci Rep. 2021 Jul 22. 11(1): 15029

Data-driven modelling approach to circadian temperature rhythm profiles in free-living conditions.

Jari Lipsanen, Liisa Kuula, Marko Elovainio, Timo Partonen, Anu-Katriina Pesonen.

The individual variation in the circadian rhythms at the physiological level is not well understood. Albeit self-reported circadian preference profiles have been consolidated, their premises are grounded on human experience, not on physiology. We used data-driven, unsupervised time series modelling to characterize distinct profiles of the circadian rhythm measured from skin surface temperature in free-living conditions. We demonstrate the existence of three distinct clusters of individuals which differed in their circadian temperature profiles. The cluster with the highest temperature amplitude and the lowest midline estimating statistic of rhythm, or rhythm-adjusted mean, had the most regular and early-timed sleep-wake rhythm, and was the least probable for those with a concurrent delayed sleep phase, or eveningness chronotype. While the clusters associated with the observed sleep and circadian preference patterns, the entirely unsupervised modelling of physiological data provides a novel basis for modelling and understanding the human circadian functions in free-living conditions.

DOI: https://doi.org/10.1038/s41598-021-94522-9

Sci Rep. 2021 Jul 21. 11(1): 14907

Astronauts well-being and possibly anti-aging improved during long-duration spaceflight.

Kuniaki Otsuka, Germaine Cornelissen, Satoshi Furukawa, Yutaka Kubo, Koichi Shibata, Koh Mizuno, Hiroshi Ohshima, Chiaki Mukai.

This study assesses how circadian rhythms of heart rate (HR), HR variability (HRV) and activity change during long-term missions in space and how they relate to sleep quality. Ambulatory 48-h ECG and 96-h actigraphy were performed four times on ten healthy astronauts (44.7 ± 6.9 years; 9 men): 120.4 ± 43.7 days (Before) launch; 21.1 ± 2.5 days (ISS01) and 143.0 ± 27.1 days (ISS02) after launch; and 86.6 ± 40.6 days (After) return to Earth. Sleep quality was determined by sleep-related changes in activity, RR-intervals, HRV HF- and VLF-components and LF-band. The circadian amplitude of HR (HR-A) was larger in space (ISS01: 12.54, P = 0.0099; ISS02: 12.77, P = 0.0364) than on Earth (Before: 10.90; After: 10.55 bpm). Sleep duration in space (ISS01/ISS02) increased in 3 (Group A, from 370.7 to 388.0/413.0 min) and decreased in 7 (Group B, from 454.0 to 408.9/381.6 min) astronauts. Sleep quality improved in Group B from 7.07 to 8.36 (ISS01) and 9.36 (ISS02, P = 0.0001). Sleep-related parasympathetic activity increased from 55.2% to 74.8% (pNN50, P = 0.0010) (ISS02). HR-A correlated with the 24-h (r = 0.8110, P = 0.0044), 12-h (r = 0.6963, P = 0.0253), and 48-h (r = 0.6921, P = 0.0266) amplitudes of the magnetic declination index. These findings suggest associations of mission duration with increased well-being and anti-aging benefitting from magnetic fluctuations.

DOI: https://doi.org/10.1038/s41598-021-94478-w

Clocks Sleep. 2021 Jul 01. 3(3): 377-386

No Effect of Chronotype on Sleepiness, Alertness, and Sustained Attention during a Single Night Shift.

Andrew M Reiter, Charli Sargent, Gregory D Roach.

The study's aim was to examine the effect of chronotype on cognitive performance during a single night shift. Data were collected from 72 (36f) young, healthy adults in a laboratory study. Participants had a 9 h sleep period (03:00-12:00) followed by an 8 h night shift (23:00-07:00). During the night shift, participants completed five test sessions, which included measures of subjective sleepiness, subjective alertness, and sustained attention (i.e., psychomotor vigilance task; PVT). Dim light melatonin onset (DLMO) was derived from saliva samples taken during the evening preceding the night shift. A tertile split of DLMO was used to determine three chronotype categories: earlier (DLMO = 20:22 ± 0:42), intermediate (DLMO = 21:31 ± 0:13), and later (DLMO = 22:54 ± 0:54). There were (a) significant main effects of test session (all p < 0.001); (b) no main effects of chronotype; and (c) no interaction effects between chronotype and test session on sleepiness, alertness, PVT response time, and PVT lapses. The results indicate that under controlled sleeping conditions, chronotype based on dim light melatonin onset did not affect nighttime performance. Differences in performance during night shift between chronotypes reported by field studies may be related to differences in the amount and/or timing of sleep before or between night shifts, rather than circadian timing.

Keywords: DLMO; KSS; PVT; chronotype; cognitive; early; intermediate; late; performance; sleepiness; subjective

DOI: https://doi.org/10.3390/clockssleep3030024