Experimental Physiology最新文献

Gravity, an invisible but constant force , challenges the regulation of blood pressure when transitioning between postures. As physiological reserve diminishes with age, individuals grow more susceptible to such stressors over time, risking inadequate haemodynamic control observed in orthostatic hypotension. This prevalent condition is characterized by drops in blood pressure upon standing; however, the contrary phenomenon of blood pressure rises has recently piqued interest. Expanding on the currently undefined orthostatic hypertension, our study uses continuous non-invasive cardiovascular data to explore the full spectrum of blood pressure profiles and their associated frailty outcomes in community-dwelling older adults. Given the richness of non-invasive beat-to-beat data, artificial intelligence (AI) offers a solution to detect the subtle patterns within it. Applying machine learning to an existing dataset of community-based adults undergoing postural assessment, we identified three distinct clusters (iOHYPO, OHYPO and OHYPER) akin to initial and classic orthostatic hypotension and orthostatic hypertension, respectively. Notably, individuals in our OHYPER cluster exhibited indicators of frailty and sarcopenia, including slower gait speed and impaired balance. In contrast, the iOHYPO cluster, despite transient drops in blood pressure, reported fewer fallers and superior cognitive performance. Surprisingly, those with sustained blood pressure deficits outperformed those with sustained rises, showing greater independence and higher Fried frailty scores. Working towards more refined definitions, our research indicates that AI approaches can yield meaningful blood pressure morphologies from beat-to-beat data. Furthermore, our findings support orthostatic hypertension as a distinct clinical entity, with frailty implications suggesting that it is worthy of further investigation.

Ageing is an escalating global health issue, with the World Health Organization (WHO) reporting that one in six individuals will be 60 years or older by the year 2030. Therefore, understanding the mechanisms of complex biological ageing processes and associated healthcare challenges has become increasingly important. Intrinsic capacity (IC), defined by WHO as the composite of all physical and mental capacities an individual possesses, can be used as a proxy for defining healthy ageing. IC has five key components: locomotion, cognition, psychological, sensory, and vitality capacity (VC). This review paper specifically focuses on exercise as an effective tool to preserve VC in ageing populations. The physiological domains of VC discussed include energy and metabolism, neuromuscular function, immune and stress response, mitochondrial function, and the methylation clock. Additionally, we highlight potential outcome measures for assessing each of these domains. This review also covers areas of focus for future research and possible interventions. We ultimately conclude that ageing is a complex, multifaceted process resulting in deficits across multiple VC components. However, regular exercise is capable of producing physiological adaptations that may be beneficial in the context of healthy ageing and improving or preserving the status of VC components.

The relationship between mechanistic target of rapamycin complex 1 (mTORC1) activation after resistance exercise and acetylcholine receptor (AChR) subunit gene expression remains largely unknown. Therefore, we aimed to investigate the effect of electrical stimulation-induced intense muscle contraction, which mimics acute resistance exercise, on the mRNA expression of AChR genes and the signalling pathways involved in neuromuscular junction (NMJ) maintenance, such as mTORC1 and muscle-specific kinase (MuSK). The gastrocnemius muscle of male adult Sprague-Dawley rats was isometrically exercised. Upon completion of muscle contraction, the rats were euthanized in the early (after 0, 1, 3, 6 or 24 h) and late (after 48 or 72 h) recovery phases and the gastrocnemius muscles were removed. Non-exercised control animals were euthanized in the basal state (control group). In the early recovery phase, Agrn gene expression increased whereas LRP4 decreased without any change in the protein and gene expression of AChR gene subunits. In the late recovery phase, Agrn, Musk, Chrnb1, Chrnd and Chrne gene expression were altered and agrin and MuSK protein expression increased. Moreover, mTORC1 and protein kinase B/Akt-histone deacetylase 4 (HDAC) were activated in the early phase but not in the late recovery phase. Furthermore, rapamycin, an inhibitor of mTORC1, did not disturb changes in AChR subunit gene expression after muscle contraction. However, rapamycin addition slightly increased AChR gene expression, while insulin did not impact it in rat L6 myotube. These results suggest that changes in the AChR subunits after muscle contraction are independent of the rapamycin-sensitive mTORC1 pathway.

Muscle spindles are stretch-sensitive mechanoreceptors found in the skeletal muscles of most four-limbed vertebrates. They are unique amongst sensory receptors in the ability to regulate their sensitivity by contraction of the intrafusal muscle fibres on which the sensory endings lie. Muscle spindles have revealed a remarkable diversity of functions, including reflex action in posture and locomotion, contributing to bodily self awareness, and influencing wound healing. What were the circumstances which gave rise to the evolution of such complex end-organs? We argue that spindles first appeared in early amniotes and only later in frogs and toads. This was considered an example of convergent evolution. Spindles in amphibians and reptiles are characterised by their simple structure, pointing to key features essential for spindle function. Spindle sensitivity in amphibians and reptiles is controlled by intrafusal fibre contractions evoked by branches of motor axons supplying extrafusal muscle. Modern phylogenetic evidence has revised our views on the origin of birds, placing them closer to the dinosaurs than had previously been thought. Birds are the only group, other than mammals, which has a dedicated fusimotor innervation of spindles, another example of convergent evolution, given the widely different origins of the two groups. One factor that may have played a role here was that both groups are endotherms, allowing motor control to develop further in an optimal internal environment. This, as well as other changes within the spindle, has led to the astonishing sophistication of motor control observed especially in many modern mammals.

Exposure to the spaceflight environment causes adaptations in most human physiological systems, many of which are thought to affect women differently from men. Since only 11.5% of astronauts worldwide have been female, these issues are largely understudied. The physiological nuances affecting the female body in the spaceflight environment remain inadequately defined since the last thorough published review on the subject. A PubMed literature search yielded over 2200 publications. Using NASA's 2014 review series 'The effects of sex and gender on adaptation to space' as a benchmark, we identified substantive advancements and persistent knowledge gaps in need of further study from the nearly 600 related articles that have been published since the initial review. This review highlights the most critical issues to mitigate medical risk and promote the success of missions to the Moon and Mars. Salient sex-linked differences observed terrestrially should be studied during upcoming missions, including increased levels of inflammatory markers, coagulation factors and leptin levels following sleep deprivation; correlation between body mass and the severity of spaceflight-associated neuro-ocular syndrome; increased incidence of orthostatic intolerance; increased severity of muscle atrophy and bone loss; differences in the incidence of urinary tract infections; and susceptibility to specific cancers after exposure to ionizing radiation. To optimize health and well-being among all astronauts, it is imperative to prioritize research that considers the physiological nuances of the female body. A more robust understanding of female physiology in the spaceflight environment will support crew readiness for Artemis missions and beyond.

Females likely experience larger performance benefits from androgenic-anabolic steroids than males. We set out to determine if there were temporal differences in select athletics (track and field) records between females and males. Exploratory aims included: (1) evaluating the improvements in female and male world records over time, and (2) investigating the influence of doping programs on male and female world records before and after 1990, when sports governing bodies began to implement random out-of-competition and systematic in-competition drug testing. We collected the top 500 performances of all time for both sexes from an online database (worldathletics.org) in four running events (100, 200, 400 and 800 m) and two throwing events (discus throw and shot-put). Data were stratified into quintiles based on world record ranking (1st to 100th, 101st to 200th, etc.). The temporal distribution of the top 100 female performers was significantly earlier than the top 100 male performers (year: 2000 ± 1 vs. 2005 ± 1, respectively; P < 0.0001). Within the event, the top performances occurred significantly earlier for females in the 800 m (year: 1995 ± 15 vs. 2003 ± 12; P = 0.0007) and shot-put (year: 1992 ± 14 vs. 2003 ± 17; P = 0.0004). Among females, world records rapidly improved through the 1980s, but following 1990, the world records ceased to improve. Geographically, there was a greater representation of countries with state-sponsored doping programs, specifically among female performances. We postulate these sex differences in the temporal distribution of top performances are likely associated with enhanced effectiveness of exogenous androgens (steroid doping) among female athletes with lower endogenous androgen hormones compared to males.

Athletes frequently compete only a few days after long-haul travel. Longitudinal real-world data on athletes' sleep and sleep-wake cycle in competitive settings remain scarce. This study assessed the impact of a long-haul travel across ∼13 time zones on sleep patterns, rest-activity circadian rhythms (RAR), and their subsequent effects on neuromuscular function and race performance in the Canadian Short-Track Speed Skating Team. Nineteen athletes (24 ± 4 years, 11 women) travelled from Montréal (UTC-5) to Asia (UTC+8, UTC+9) for World Cup races between 2017 and 2019. Actigraphy data were collected before (Baseline) and during travel, during the stay in Asia (SIA), and during competition days. RAR were computed using cosinor analyses on accelerometry data with 24 h phase periods. Countermovement jump height (CMJ) was measured in a subsample (n = 10). Compared to baseline (7:08 ± 0:53), athletes obtained less sleep during travel (6:16 ± 1:27) and competition days (6:35 ± 1:10), and more during SIA (7:32 ± 0:46; time effect P < 0.0001). Sleep efficiency and CMJ were greater in SIA than baseline (P = 0.007 and P = 0.0004, respectively). During SIA, sleep time increased by 9 min per night until the fifth day (P < 0.0001), with a slight decrease in sleep efficiency (P = 0.005) and an increase in CMJ (P < 0.0001). For RAR, mean activity peaked on day 2, shifting from late evening to ∼15:00. Race performance was not different from other races of the same season (P > 0.254). Our results demonstrated that, despite the possible sleep debt from the long-haul travel, athletes recovered within 5 days, highlighting their adaptability to manage sleep debt and jetlag without impacting competitive outcomes.

Intestinal ischaemia-reperfusion (I/R) is a common clinical pathology with high incidence and mortality rates. However, the mechanisms underlying intestinal I/R injury remain unclear. In this study, we investigated the role and mechanism of chitinase 3-like 1 (CHI3L1) during intestinal I/R injury. Therefore, we analysed the expression levels of CHI3L1 in the intestinal tissue of an intestinal I/R rat model and explored its effects and mechanism in a hypoxia-reoxygenation (H/R) IEC-6 cell model. We found that intestinal I/R injury elevated CHI3L1 levels in the serum, ileum and duodenum, whereas H/R enhanced CHI3L1 expression in IEC-6 cells. The H/R-induced inhibition of proliferation and apoptosis was alleviated by CHI3L1 knockdown and aggravated by CHI3L1 overexpression. In addition, CHI3L1 knockdown alleviated, and CHI3L1 overexpression aggravated, the H/R-induced inflammatory response and oxidative stress. Mechanistically, CHI3L1 overexpression weakened the activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway, suppressed the nuclear translocation of Nrf2, and promoted the nuclear translocation of nuclear factor κB (NF-κB). Moreover, CHI3L1 knockdown had the opposite effect on the PI3K/AKT pathway, Nrf2, and NF-κB. Moreover, the PI3K inhibitor LY294002 blocked the effect of CHI3L1 knockdown on the H/R-induced inhibition of proliferation, apoptosis, inflammatory response and oxidative stress. In conclusion, CHI3L1 expression was induced during intestinal I/R and H/R injury in IEC-6 cells, and CHI3L1 overexpression aggravated H/R injury in IEC-6 cells by inhibiting the PI3K/AKT signalling pathway. Therefore, CHI3L1 may be an effective target for controlling intestinal I/R injury.

This study aimed to determine the difference in motor unit (MU) firing pattern between hypertensive and normotensive individuals, and the relationship between MU firing pattern and post-exercise blood pressure (BP) response in older individuals. Fourteen older untreated (systolic/diastolic BP (SBP/DBP) ≥ 130/80 mmHg, 76 (5) years), 11 treated hypertensive (78 (4) years) and 14 normotensive (SBP/DBP < 130/80 mmHg, 71 (4) years) individuals were studied. Participants performed ramp-up exercises until 50% of maximal voluntary contraction (MVC) of knee extension and five MVCs. During the ramp-up exercise, high-density surface electromyography signals were recorded and each MU firing rate (FR) and recruitment threshold was assessed. The slope of the linear regression between MUFRs and recruitment thresholds was calculated to assess the MU firing pattern. Pre- and post-exercise blood pressure was measured. Change in (∆)SBP from pre- to post-exercise was greater in treated hypertensive than untreated hypertensive individuals (P = 0.026). MUFR was lower in treated hypertensive than untreated hypertensive and normotensive individuals (P < 0.001). Although the slope was not significantly different between groups (P = 0.294), FRs of larger MUs were lower than those of smaller MUs in treated hypertensive and normotensive individuals (P < 0.05) but sustained in untreated hypertensive individuals. The FRs of larger MUs and slope were positively correlated with the ∆SBP only in hypertensive individuals (r = 0.768 and 0.715; P = 0.044 and 0.020). MUFR was lower in treated hypertensive than untreated hypertensive and normotensive individuals. Furthermore, MU firing patterns were associated with the ∆SBP after exercise in older untreated hypertensive individuals, but this relationship was not observed in treated hypertensive and normotensive individuals.