Preprint Thermosensitivity of translation underlies the mammalian nocturnal-diurnal switch, 2023, Beale et al.

[SNT Gatchaman]

Thermosensitivity of translation underlies the mammalian nocturnal-diurnal switch
Andrew David Beale; Nina M Rzechorzek; Andrei Mihut; Aiwei Zeng; Nicola J Smyllie; Violetta Pilorz; Rose Richardson; Mads F Bertlesen; Nathan R James; Shaline V Fazal; Zanna Voysey; Jerry Pelletier; Priya Crosby; Sew Y Peak-Chew; Madeline A Lancaster; Roelof A. Hut; John S O'Neill

Early mammals were nocturnal until the Cretaceous-Paleogene extinction facilitated their rapid expansion into daytime niches.

Diurnality subsequently evolved multiple times, independently, but the mechanisms facilitating this switch are unknown. We found that physiological daily temperature shifts oppositely affect circadian clock rhythms in nocturnal versus diurnal mammals. This occurs through a cell-intrinsic signal inverter, mediated by global differences in protein phosphorylation, and effected at the level of bulk protein synthesis rates, with diurnal translation rate being less thermosensitive than nocturnal. Perturbations that reduce translational initiation or mTOR activity are sufficient to trigger the nocturnal-to-diurnal switch at the cellular, tissue, and organismal scale.

Our results suggest a convergent selection pressure to attain diurnality by reducing the effect of temperature-dependent changes in protein synthesis on circadian clocks.

One sentence summary: Recalibrating the thermosensitivity of protein synthesis drives daytime-selective activity in mammals.

Link | PDF (Preprint: BioRxiv)

 

[SNT Gatchaman]

Somewhat oblique title, but interesting read to see links between nutrient sensing, mTORC and circadian rhythms.

Early mammals were nocturnal (night active) until the extinction of the diurnal (day active) dinosaurs facilitated a rapid expansion into daytime niches. Diurnality subsequently arose multiple times, independently, from diverse and distant nocturnal lineages. No mechanistic basis for the switch between nocturnality and diurnality is known, though evidently some change in the relationship between internal circadian clocks and external daily rhythms is required.

Despite the 76 million years that separate nocturnal mice and diurnal humans from their common ancestor, the same cell-autonomous circadian clock mechanism operates in both mouse and human cells. Daily rhythms of gene expression, proteome renewal, and myriad cellular functions depend on cell-intrinsic ~24h oscillations in the production of PERIOD (PER) proteins; where the changing activity of PER over time effectively determines the biological time-of-day.

Similarly, the hypothalamic suprachiasmatic nucleus (SCN) functions very similarly in diurnal and nocturnal mammals, receiving light input directly from the eyes to generate an internal representation of solar time. However, unlike the SCN, PER oscillations in peripheral cells and tissues are oppositely organised between diurnal and nocturnal mammals, and instead vary with daily systemic signals that habitually coincide with the transition from resting, fasting and lower body temperature to activity, feeding and higher body temperature, rather than external solar time.

Thus, excepting the SCN, the major behavioural and physiological daily rhythms in mammals are set to opposite times of day between nocturnal and diurnal mammals, suggesting a switch downstream of the SCN [suprachiasmatic nucleus]. How diurnal mammals integrate the same environmental cues to achieve an inversion of organismal and cellular physiology compared with nocturnal mammals is an open question, but is critical for understanding mechanisms of internal synchrony that are pivotal for long-term health.

 

[SNT Gatchaman]

we test the functional consequences of modifying protein synthesis rates on temporal niche in vivo, and pinpoint mTOR activity as a nexus of signalling that integrates bioenergetic and temperature cues into the cellular clock.

 

[Trish]

I've only read the bits quoted so may be off track here, but I wonder whether deliberately altering eating and temperature timings affect sleeping timings. For example some people say that if you're changing time zones, the quickest way to get over jet lag and adjust to your new time zone is to start eating meals in the new time zone pattern early. And separately some people recommend a warm bath at bedtime.

 

[Hoopoe]

I've only read the bits quoted so may be off track here, but I wonder whether deliberately altering eating and temperature timings affect sleeping timings

From what I understood the liver has its own circadian rythm that is influenced by and influences feeding and fasting behaviour.

I learned about this by observing how I could not handle skipping meals around 17:00 but could easily tolerate moving my dinner to 17:00 and not eating afterwards (instead of eating around 19:00-20:00). And this earlier dinner also seemed to help me fall asleep because eating for me is very energizing for a few hours. Once this observation was made, I began reading about circadian clocks and learned about the liver circadian clock. I'm not sure if changing the feeding time alters the sleep-wake rythms but it seems plausible.

Edit: it seems that the liver does have some influence

Liver cells control our biological clock
https://www.cnrs.fr/en/liver-cells-control-our-biological-clock

 

[Hutan]

They seem to conclude that humans, as diurnal mammals and unlike nocturnal animals, aren't very sensitive to temperature changes with respect to circadian rhythms. Nevertheless, there is still some sensitivity, so a cooler room temperature at night to facilitate sleep is probably a good idea.

At the whole organism level, our findings results agree with the circadian thermo- energetics (CTE) hypothesis for conditional niche-switching in several different mammals (4). CTE states that, for homeothermic mammals, nocturnal activity patterns are more costly than diurnal patterns, since nocturnal animals have higher energy requirements that compensate for the greater heat loss of being active in the (cold) night (104, 117, 118). Diurnality arises as an energy saving measure when food availability is scarce, which outcompetes the extra predation pressure of being active by day (119).

This isn't relevant to ME/CFS at all, but I do think this paper has a 'high latitude' bias. In many environments, diurnal activity can be more costly for homeothermic animals. The hot day can be more of a problem than the cooler night. That's likely to become true in an increasing proportion of Earth's surface over time.

Also, I don't think diurnality necessarily arises 'as an energy saving measure when food availability is scarce'. I have seen forest animals, prey species, that were nocturnal become diurnal over a matter of years when hunting pressure was removed and forest logging stopped, that is when food availability increased and was less risky to obtain. Also, mice in mast seeding years become diurnal, because they can. Their numbers increase so rapidly in response to the high food availability that the predation pressure from the slower breeding predators is reduced.

In many environments, I don't think 'energy saving' is a particularly strong driver of being diurnal, rather, the drivers are food availability and the risk of being killed.

 

[SNT Gatchaman]

Also some interesting implications for translational research when studying mice and trying to apply in human clinical trials. Eg Potential circadian effects on translational failure for neuroprotection (2020, Nature) —

Neuroprotectant strategies that have worked in rodent models of stroke have failed to provide protection in clinical trials. Here we show that the opposite circadian cycles in nocturnal rodents versus diurnal humans may contribute to this failure in translation. We tested three independent neuroprotective approaches—normobaric hyperoxia, the free radical scavenger α-phenyl-butyl-tert-nitrone (αPBN), and the N-methyl-d-aspartic acid (NMDA) antagonist MK801—in mouse and rat models of focal cerebral ischaemia. All three treatments reduced infarction in day-time (inactive phase) rodent models of stroke, but not in night-time (active phase) rodent models of stroke [...] These findings suggest that the influence of circadian rhythm on neuroprotection must be considered for translational studies in stroke and central nervous system diseases.

 

[boolybooly]

I think this is really badly written.

We recapitulate temporal niche selection in vitro and reveal its cellular and molecular bases.

And this is hyperbolic Malapropism to the point of falsehood. Recapitulation means following the preexisting pattern of development, which this did not. It achieved a superficially comparable behaviour through in vitro manipulation of lymphocytes with metabolic blockers.

recapitulation : the repetition of an evolutionary or other process during development or growth.

( edit to add - Likewise, eliciting a diurnal response by starving normally nocturnal mice is not shown to be the recapitulation of the diurnal evolution of other taxa in former epochs. This behavioural response is a current potentially adaptive response to environmental conditions but that does not mean it is due to the same unidentified genetic changes which allowed the selection of diurnal behaviour in other species. The claim of recapitulation is overblown and misconceived. Even if they meant that the mouse reverted to the diurnal behaviour which preceded the evolution of nocturnal behaviour, that is not recapitulation, I don't know the correct term but it would carry the sense of reversion.)

I read obscurantist word salad aka BS.

(Sorry I know that is rude and bad tempered. Mea culpa.)