RESUMO
Background: The Montane® Yukon Arctic Ultra (YAU) is one of the longest (690 km) and coldest (+10.6°C-43.9°C) ultramarathons worldwide. Taking part in an ultramarathon is associated with great physiological and psychological stress, which can affect one's mood, level of hormones, and peptides. The current study aimed to identify relationships between peptides, hormones, and mood states in participants during this ultramarathon. Methods: The study cohort consisted of 36 participants (19 men, 17 women, 38.64 ± 9.12 years) split into a finisher (n = 10), non-finisher (n = 19), and control group (n = 7). Data were collected at four time points: baseline (PRE), during (D1 after 277 km, D2 after 383 km), and after the race (POST). Questionnaires were used to assess ratings of perceived exertion (RPE), total quality of recovery (TQR), and profile of mood states (POMS-SF). Serum NPY, leptin, adiponectin, and cortisol were measured. Results: Among non-finishers, scores for confusion, anger, depression, and tension-anxiety (PRE vs. D2, p < 0.05) increased, while vigor decreased (PRE vs. D1, p < 0.05). In contrast, finishers' tension-anxiety scores decreased (PRE vs. D1, p < 0.05). Fatigue increased in finishers (PRE vs. POST, p < 0.05) and non-finishers (PRE vs. D1, p < 0.05). In non-finishers, depressive mood correlated positively with leptin, anger, and confusion at several time points (p < 0.001). In finishers, NPY correlated with TQR at PRE (p < 0.05), while leptin correlated negatively with TQR at POST (p < 0.05). Tension-anxiety correlated highly with perceived exertion in non-finishers (p < 0.001) and with cortisol in finishers (p < 0.05) and non-finishers (p < 0.001). In finishers, confusion correlated negatively with NPY (p < 0.01). Conclusion: The study reveals an essential interplay between hormones and mood states affecting performance: Leptin was associated with anger and a depressive mood state in non-finishers and worse recovery in finishers. In contrast, NPY appeared linked to a lower confusion score and heightened recovery in finishers. A simultaneous increase in depressed mood, anger, tension-anxiety, and confusion might harm performance and lead to race failure.
RESUMO
The mammalian circadian clock and the cell cycle are two major biological oscillators whose coupling influences cell fate decisions. In the present study, we use a model-driven experimental approach to investigate the interplay between clock and cell cycle components and the dysregulatory effects of RAS on this coupled system. In particular, we focus on the Ink4a/Arf locus as one of the bridging clock-cell cycle elements. Upon perturbations by the rat sarcoma viral oncogene (RAS), differential effects on the circadian phenotype were observed in wild-type and Ink4a/Arf knock-out mouse embryonic fibroblasts (MEFs), which could be reproduced by our modelling simulations and correlated with opposing cell cycle fate decisions. Interestingly, the observed changes can be attributed to in silico phase shifts in the expression of core-clock elements. A genome-wide analysis revealed a set of differentially expressed genes that form an intricate network with the circadian system with enriched pathways involved in opposing cell cycle phenotypes. In addition, a machine learning approach complemented by cell cycle analysis classified the observed cell cycle fate decisions as dependent on Ink4a/Arf and the oncogene RAS and highlighted a putative fine-tuning role of Bmal1 as an elicitor of such processes, ultimately resulting in increased cell proliferation in the Ink4a/Arf knock-out scenario. This indicates that the dysregulation of the core-clock might work as an enhancer of RAS-mediated regulation of the cell cycle. Our combined in silico and in vitro approach highlights the important role of the circadian clock as an Ink4a/Arf-dependent modulator of oncogene-induced cell fate decisions, reinforcing its function as a tumour-suppressor and the close interplay between the clock and the cell cycle network.
