bims-ciryme 2024-10-20 papers

Issue of 2024‒10‒20
four papers selected by
Gabriela Da Silva Xavier, University of Birmingham

Proc Natl Acad Sci U S A. 2024 Oct 22. 121(43): e2405924121

Brighter nights and darker days predict higher mortality risk: A prospective analysis of personal light exposure in >88,000 individuals.

Daniel P Windred, Angus C Burns, Jacqueline M Lane, Patrick Olivier, Martin K Rutter, Richa Saxena, Andrew J K Phillips, Sean W Cain.

Light enhances or disrupts circadian rhythms, depending on the timing of exposure. Circadian disruption contributes to poor health outcomes that increase mortality risk. Whether personal light exposure predicts mortality risk has not been established. We therefore investigated whether personal day and night light, and light patterns that disrupt circadian rhythms, predicted mortality risk. UK Biobank participants (N = 88,905, 62.4 ± 7.8 y, 57% female) wore light sensors for 1 wk. Day and night light exposures were defined by factor analysis of 24-h light profiles. A computational model of the human circadian pacemaker was applied to model circadian amplitude and phase from light data. Cause-specific mortality was recorded in 3,750 participants across a mean (±SD) follow-up period of 8.0 ± 1.0 y. Individuals with brighter day light had incrementally lower all-cause mortality risk (adjusted-HR ranges: 0.84 to 0.90 [50 to 70th light exposure percentiles], 0.74 to 0.84 [70 to 90th], and 0.66 to 0.83 [90 to 100th]), and those with brighter night light had incrementally higher all-cause mortality risk (aHR ranges: 1.15 to 1.18 [70 to 90th], and 1.21 to 1.34 [90 to 100th]), compared to individuals in darker environments (0 to 50th percentiles). Individuals with lower circadian amplitude (aHR range: 0.90 to 0.96 per SD), earlier circadian phase (aHR range: 1.16 to 1.30), or later circadian phase (aHR range: 1.13 to 1.20) had higher all-cause mortality risks. Day light, night light, and circadian amplitude predicted cardiometabolic mortality, with larger hazard ratios than for mortality by other causes. Findings were robust to adjustment for age, sex, ethnicity, photoperiod, and sociodemographic and lifestyle factors. Minimizing night light, maximizing day light, and keeping regular light-dark patterns that enhance circadian rhythms may promote cardiometabolic health and longevity.

Keywords: cardiometabolic; circadian disruption; light at night; light sensor; longevity

DOI: https://doi.org/10.1073/pnas.2405924121

Elife. 2024 Oct 15. pii: RP97754. [Epub ahead of print]13

Light-driven synchronization of optogenetic clocks.

Maria Cristina Cannarsa, Filippo Liguori, Nicola Pellicciotta, Giacomo Frangipane, Roberto Di Leonardo.

Synthetic genetic oscillators can serve as internal clocks within engineered cells to program periodic expression. However, cell-to-cell variability introduces a dispersion in the characteristics of these clocks that drives the population to complete desynchronization. Here, we introduce the optorepressilator, an optically controllable genetic clock that combines the repressilator, a three-node synthetic network in E. coli, with an optogenetic module enabling to reset, delay, or advance its phase using optical inputs. We demonstrate that a population of optorepressilators can be synchronized by transient green light exposure or entrained to oscillate indefinitely by a train of short pulses, through a mechanism reminiscent of natural circadian clocks. Furthermore, we investigate the system's response to detuned external stimuli observing multiple regimes of global synchronization. Integrating experiments and mathematical modeling, we show that the entrainment mechanism is robust and can be understood quantitatively from single cell to population level.

Keywords: E. coli; computational biology; nonlinear dynamics; optogenetics; physics of living systems; synthetic biology; systems biology

DOI: https://doi.org/10.7554/eLife.97754

Physiol Behav. 2024 Oct 10. pii: S0031-9384(24)00259-2. [Epub ahead of print]287 114711

Obesity alters circadian and behavioral responses to constant light in male mice.

Meredith E Burns, Fernanda Medeiros Contini, Julie M Michaud, Caitlin T Waring, John C Price, Alexander T McFarland, Samantha G Burke, Cloey A Murphy, Grace E Guindon, Merideth K Krevosky, Joseph A Seggio.

Exposure to artificial light during the night is known to promote disruption to the biological clock, which can lead to impaired mood and metabolism. Metabolic hormone secretion is modulated by the circadian pacemaker and recent research has shown that hormones such as insulin and leptin can also directly affect behavioral outcomes and the circadian clock. In turn, obesity itself is known to modulate the circadian rhythm and alter emotionality. This study investigated the behavioral and metabolic effects of constant light exposure in two models of obesity - a leptin null mutant (OB) and diet-induced obesity via high-fat diet. For both experiments, mice were placed into either a standard Light:Dark cycle (LD) or constant light (LL) and their circadian locomotor rhythms were continuously monitored. After 10 weeks of exposure to their respective lighting conditions, all mice were subjected to an open field assay to assess their explorative behaviors. Their metabolic hormone levels and inflammation levels were also measured. Behaviorally, exposure to constant light led to increased period lengthening and open field activity in the lean mice compared to both obesity models. Metabolically, LL led to increased cytokine levels and poorer metabolic outcomes in both lean and obese mice, sometimes exacerbating the metabolic issues in the obese mice, independent of weight gain. This study illustrates that LL can produce altered behavioral and physiological outcomes, even in lean mice. These results also indicate that obesity induced by different reasons can lead to shortened circadian rhythmicity and exploratory activity when exposed to chronic light.

Keywords: Behavior; Circadian rhythm; High-fat diet; Inflammation; Leptin; Mouse

DOI: https://doi.org/10.1016/j.physbeh.2024.114711

Cell Rep. 2024 Oct 15. pii: S2211-1247(24)01216-6. [Epub ahead of print]43(10): 114865

Hepatocyte Period 1 dictates oxidative substrate selection independent of the core circadian clock.

Jiameng Sun, Yiming Zhang, Joshua A Adams, Cassandra B Higgins, Shannon C Kelly, Hao Zhang, Kevin Y Cho, Ulysses G Johnson, Benjamin M Swarts, Shun-Ichi Wada, Gary J Patti, Leah P Shriver, Brian N Finck, Erik D Herzog, Brian J DeBosch.

Organisms integrate circadian and metabolic signals to optimize substrate selection to survive starvation, yet precisely how this occurs is unclear. Here, we show that hepatocyte Period1 (Per1) is selectively induced during fasting, and mice lacking hepatocyte Per1 fail to initiate autophagic flux, ketogenesis, and lipid accumulation. Transcriptomic analyses show failed induction of the fasting hepatokine Fgf21 in Per1-deficient mice, and single-nucleus multiome sequencing defines a putative responding hepatocyte subpopulation that fails to induce the chromatin accessibility near the Fgf21 locus. In vivo isotopic tracing and indirect calorimetry demonstrate that hepatocyte Per1-deficient mice fail to transit from oxidation of glucose to fat, which is completely reversible by exogenous FGF21 or by inhibiting pyruvate dehydrogenase. Strikingly, disturbing other core circadian genes does not perturb Per1 induction during fasting. We thus describe Per1 as an important mechanism by which hepatocytes integrate internal circadian rhythm and external nutrition signals to facilitate proper fuel utilization.

Keywords: CP: Metabolism; circadian clock; fasting; glucose oxidation; liver metabolism; metabolite tracing; single-nucleus multiome sequencing

DOI: https://doi.org/10.1016/j.celrep.2024.114865