Michal Zeman

The aim of this study was to assess the relationship between long‐term endurance running training and daily variation in testosterone, which is known to diminish during ageing, in a comparative, cross‐sectional study. We recruited 45 male participants into four groups [young athletes (YA), young sedentary (YS), master athletes (MA) and elderly sedentary (ES)] and performed anthropometry, strength and ergometry tests. Morning (AM) and afternoon (PM) venous blood samples were collected to evaluate testosterone daily variation, sex hormone binding globulin (SHBG), cortisol and estradiol, and we calculated free testosterone, bioavailable testosterone and the free androgen index. Two‐way and three‐way ANOVAs followed by Bonferroni's multiple comparisons tests were performed. The free testosterone and free androgen index showed a significant PM decrease in the MA group ( P = 0.0009 and 0.0021, respectively), comparable to YA and YS; however, in the ES group there was no difference between AM and PM values (both P  > 0.9999). SHBG levels were significantly increased by both the age ( P = 0.0001) and activity ( P = 0.0016) factors, leading to a significant decrease in free testosterone, bioavailable testosterone and free androgen index. In the peak power output parameters of ergometry, expressed in both absolute and relative values, MA achieved values comparable to YS, significantly higher than ES ( P = 0.0020 and P  < 0.0001, respectively) and lower than YA ( P  < 0.0001). In conclusion, long‐term endurance running training in elderly men might be associated with the presence of daily variation in free testosterone and higher performance levels in comparison to sedentary counterparts, but it might contribute to age‐related changes in SHBG and related testosterone fraction levels.

Diurnal strength fluctuations and the effects of time-of-day-specific training are well-documented in young adults but unclear in elderly women. This study investigated the effects of time-of-day-specific concurrent resistance-aerobic training on muscle strength, bone mass, and functional performance in elderly women. Twenty-six women (65-85 years) were randomized into morning (MTG), afternoon (ATG) and control (CON) groups. Training groups completed 12 weeks of concurrent resistance-aerobic training (3 sessions/week, factor of time). Outcomes included maximal knee extension torque (measured AM/PM, factor of test time), bone mineral density (DXA), and functional tests (30-s chair stand, Five Times Sit-to-Stand and Maximal gait speed). Analysis of strength confirmed a preserved diurnal rhythm, with morning performance deficit present (test time: p=0.0129). The group and time factors interaction approached significance (p=0.0624), further test showed that only ATG differed significantly from the CON, with broader improvement than MTG. The functional performance significantly improved in all tests (p<0.0001, p=0.0002, p=0.0200, respectively) compared to baseline, with no difference between groups. The bone mass parameters remained unchanged. The time-of-day-specific concurrent training improved strength and functional performance in both training groups with afternoon training producing superior strength gains compared to morning training. Unchanged bone parameters suggest longer interventions might be needed for osteogenic effects.

Constant light (LL) disrupts biological rhythms, although more data are available on circadian than on ultradian rhythms. LL has been linked to elevated blood pressure (BP), although most evidence comes from tail-cuff plethysmography in males. However, in nocturnal animals, LL should suppress activity, increase sleep, and lower BP. Therefore, the aim of this study is to provide a comprehensive analysis of the impact of LL on (1) cardiovascular parameters and sleep and (2) circadian and ultradian variability in female rats. We used telemetry for continuous monitoring of heart rate (HR), BP, and locomotor and sleep-wake activity in female rats exposed to LL for four weeks. LL progressively reduced basal systolic BP and HR and weakened the strength of circadian rhythms. Moreover, the loss of daily variability enhanced the acute cardiovascular response. Spectral analysis revealed disrupted ultradian rhythms, with HR power shifting from longer (~7–9 h) to shorter (~1–3 h) periods and locomotor activity showing a parallel decline, including a complete loss of 7–9 h rhythms by week 4. HR variability and baroreflex analysis showed parasympathetic dominance under LL. Sleep analysis revealed significant sleep disruption, characterised by altered distribution of sleep–wake states, reduced non-REM sleep during the light phase, increased fragmentation, and a complete loss of circadian organisation. LL reduced BP in female rats despite leaving total sleep duration largely unchanged, while markedly disrupting cardiovascular circadian and ultradian variability and sleep architecture. These findings suggest that LL-induced chronodisruption imposes a maladaptive physiological load also in nocturnal rodents.

Endothelial cells play a key role in maintaining vascular homeostasis, and disruption of their function contributes to endothelial dysfunction. The underlying mechanisms have been studied using primary endothelial cells (HUVEC) and hybrid endothelial cell line EA.hy926, and their responses to disrupting agents should be similar. In this study, we investigated the effects of elevated homocysteine (HCY) concentrations, a risk factor for endothelial dysfunction development, in both cell types. Using multiple approaches, the inhibitory effect of HCY was consistently observed in HUVEC. In contrast, EA.hy926 cells exhibited increased proliferation and viability at lower doses, whereas the highest dose (10 mM) was inhibitory to both cell types. The bimodal and stimulatory effect of HCY in EA.hy926 cells was abolished by aminooxyacetic acid, a dominant inhibitor of cystathionine beta-synthase suggesting that decreased HCY levels and the formation of glutathione and hydrogen sulfide protected these cells. No such effect was found in HUVEC. The PI3K/Akt and MAPK/ERK signaling pathways were differentially activated in both models, suggesting their differing contributions to the HCY response. These findings reveal the cell-specific mechanisms of HCY-induced endothelial disruption, contributing to a better understanding of the mechanisms underlying endothelial dysfunction.

Melatonin is synthesised during the dark phase of the day, and its biosynthesis is inhibited by light. Exogenously supplied melatonin has been reported to have hypotensive effects. However, in animal experiments, melatonin is usually administered in one high dose and blood pressure (BP) is almost exclusively measured by plethysmography during the light phase of the day. We tested the effects of melatonin administration in drinking water during the dark phase of the day at different concentrations (2–45 mg/kg/12 h) for three weeks and telemetrically measured haemodynamic variables in spontaneously hypertensive rats (SHR). We measured gene and protein expression in the hypothalamus, brainstem, kidney and adrenal gland. We did not observe a BP decrease even at the highest melatonin concentration. We observed a dose-dependent increase in the percent recovery point and a decrease in dP/dt_max, particularly during the light phase at lower doses. The effects on the autonomic nervous system and baroreflex were equivocal, with changes observed in both experimental and placebo groups. Melatonin dose-dependently decreased vasopressin expression in the supraoptic nuclei. In the adrenal gland, melatonin increased tyrosine hydroxylase expression. In the kidney, low melatonin doses increased endothelial nitric oxide synthase, while higher doses decreased CD68 levels. Our results do not confirm the hypotensive effects of melatonin in SHR. The potential beneficial effects of melatonin could result from a long-term impact on various organs involved in BP regulation and interaction with multiple molecular pathways, some of which may manifest in improved cardiovascular health in the long term.

Artificial light at night (ALAN) disrupts 24-h variability of blood pressure, but the molecular mechanisms underlying these effects are unknown. Therefore, we analysed the daily variability of pulse pressure, the maximum value of acceleration rate of aortic pressure (dP/dt_(max)) measured by telemetry and protein expression in the thoracic aorta of normotensive male rats exposed to ALAN (1–2 lx) for 3 weeks. Daily, 24-h variability of pulse pressure and dP/dt_(max) was observed during a regular light/dark regimen with higher values during the dark compared to the light phase of the day. ALAN suppressed 24-h variability and enhanced ultradian ((max) in duration-dependent manners. From beat-to-beat blood pressure variability, ALAN decreased low-frequency bands (a sympathetic marker) and had minimal effects on high-frequency bands. At the molecular level, ALAN decreased angiotensin II receptor type 1 expression and reduced 24-h variability. ALAN caused the appearance of 12-h oscillations in transforming growth factor β1 and fibulin 4. Expression of sarco/endoplasmic reticulum Ca²⁺-ATPase type 2 was increased in the middle of the light and dark phase of the day, and ALAN did not affect its daily and 12-h variability. In conclusion, ALAN suppressed 24-h variability of pulse pressure and dP/dt_(max), decreased the power of low-frequency bands and differentially affected the expression of specific proteins in the rat thoracic aorta. Suppressed 24-h oscillations by ALAN underline the pulsatility of individual endocrine axes with different periods, disrupting the cardiovascular control of central blood pressure.

Biological clocks are evolved time-keeping systems by which organisms rhythmically coordinate physiology within the body, and align it with rhythms in their environment. Clocks are highly sensitive to light and are at the interface of several major endocrine pathways. Worryingly, exposure to artificial-light-at-night (ALAN) is rapidly increasing in ever more extensive parts of the world, with likely impact on wild organisms mediated by endocrine–circadian pathways. In this overview, we first give a broad-brush introduction to biological rhythms. Then, we outline interactions between the avian clock, endocrine pathways, and environmental and internal modifiers. The main focus of this review is on the circadian hormone, melatonin. We summarize information from avian field and laboratory studies on melatonin and its relationships with behaviour and physiology, including often neglected developmental aspects. When exposed to ALAN, birds are highly vulnerable to disruption of behavioural rhythms and of physiological systems under rhythmic control. Several studies suggest that melatonin is likely a key mediator for a broad range of effects. We encourage further observational and experimental studies of ALAN impact on melatonin, across the full functional range of this versatile signalling molecule, as well as on other candidate compounds at the endocrine–circadian interface. This article is part of the theme issue ‘Endocrine responses to environmental variation: conceptual approaches and recent developments’.