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International Journal of Molecular... Jan 2023High-altitude illnesses (HAIs) result from acute exposure to high altitude/hypoxia. Numerous molecular mechanisms affect appropriate acclimatization to hypobaric and/or... (Review)
Review
High-altitude illnesses (HAIs) result from acute exposure to high altitude/hypoxia. Numerous molecular mechanisms affect appropriate acclimatization to hypobaric and/or normobaric hypoxia and curtail the development of HAIs. The understanding of these mechanisms is essential to optimize hypoxic acclimatization for efficient prophylaxis and treatment of HAIs. This review aims to link outcomes of molecular mechanisms to either adverse effects of acute high-altitude/hypoxia exposure or the developing tolerance with acclimatization. After summarizing systemic physiological responses to acute high-altitude exposure, the associated acclimatization, and the epidemiology and pathophysiology of various HAIs, the article focuses on molecular adjustments and maladjustments during acute exposure and acclimatization to high altitude/hypoxia. Pivotal modifying mechanisms include molecular responses orchestrated by transcription factors, most notably hypoxia inducible factors, and reciprocal effects on mitochondrial functions and REDOX homeostasis. In addition, discussed are genetic factors and the resultant proteomic profiles determining these hypoxia-modifying mechanisms culminating in successful high-altitude acclimatization. Lastly, the article discusses practical considerations related to the molecular aspects of acclimatization and altitude training strategies.
Topics: Humans; Altitude; Proteomics; Altitude Sickness; Hypoxia; Acclimatization
PubMed: 36675214
DOI: 10.3390/ijms24021698 -
Autonomic Neuroscience : Basic &... Apr 2016This review examines the cardiovascular adaptations along with total body water and plasma volume adjustments that occur in parallel with improved heat loss responses... (Review)
Review
This review examines the cardiovascular adaptations along with total body water and plasma volume adjustments that occur in parallel with improved heat loss responses during exercise-heat acclimation. The cardiovascular system is well recognized as an important contributor to exercise-heat acclimation that acts to minimize physiological strain, reduce the risk of serious heat illness and better sustain exercise capacity. The upright posture adopted by humans during most physical activities and the large skin surface area contribute to the circulatory and blood pressure regulation challenge of simultaneously supporting skeletal muscle blood flow and dissipating heat via increased skin blood flow and sweat secretion during exercise-heat stress. Although it was traditionally held that cardiac output increased during exercise-heat stress to primarily support elevated skin blood flow requirements, recent evidence suggests that temperature-sensitive mechanisms may also mediate an elevation in skeletal muscle blood flow. The cardiovascular adaptations supporting this challenge include an increase in total body water, plasma volume expansion, better sustainment and/or elevation of stroke volume, reduction in heart rate, improvement in ventricular filling and myocardial efficiency, and enhanced skin blood flow and sweating responses. The magnitude of these adaptations is variable and dependent on several factors such as exercise intensity, duration of exposure, frequency and total number of exposures, as well as the environmental conditions (i.e. dry or humid heat) in which acclimation occurs.
Topics: Acclimatization; Adaptation, Physiological; Animals; Exercise; Heat Stress Disorders; Hot Temperature; Humans; Sweating
PubMed: 26905458
DOI: 10.1016/j.autneu.2016.02.002 -
Journal of the International Society of... Jan 2020The ergogenic effects of supplemental carbohydrate on aerobic exercise performance at high altitude (HA) may be modulated by acclimatization status. Longitudinal... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The ergogenic effects of supplemental carbohydrate on aerobic exercise performance at high altitude (HA) may be modulated by acclimatization status. Longitudinal evaluation of potential performance benefits of carbohydrate supplementation in the same volunteers before and after acclimatization to HA have not been reported.
PURPOSE
This study examined how consuming carbohydrate affected 2-mile time trial performance in lowlanders at HA (4300 m) before and after acclimatization.
METHODS
Fourteen unacclimatized men performed 80 min of metabolically-matched (~ 1.7 L/min) treadmill walking at sea level (SL), after ~ 5 h of acute HA exposure, and after 22 days of HA acclimatization and concomitant 40% energy deficit (chronic HA). Before, and every 20 min during walking, participants consumed either carbohydrate (CHO, n = 8; 65.25 g fructose + 79.75 g glucose, 1.8 g carbohydrate/min) or flavor-matched placebo (PLA, n = 6) beverages. A self-paced 2-mile treadmill time trial was performed immediately after completing the 80-min walk.
RESULTS
There were no differences (P > 0.05) in time trial duration between CHO and PLA at SL, acute HA, or chronic HA. Time trial duration was longer (P < 0.05) at acute HA (mean ± SD; 27.3 ± 6.3 min) compared to chronic HA (23.6 ± 4.5 min) and SL (17.6 ± 3.6 min); however, time trial duration at chronic HA was still longer than SL (P < 0.05).
CONCLUSION
These data suggest that carbohydrate supplementation does not enhance aerobic exercise performance in lowlanders acutely exposed or acclimatized to HA.
TRIAL REGISTRATION
NCT, NCT02731066, Registered March 292,016.
Topics: Acclimatization; Altitude; Carbohydrates; Dietary Supplements; Exercise; Heart Rate; Humans; Longitudinal Studies; Male; Oxygen Consumption; Physical Exertion
PubMed: 31918720
DOI: 10.1186/s12970-020-0335-2 -
Plant Communications Nov 2020
Topics: Acclimatization; Adaptation, Physiological; Biological Evolution; Plants
PubMed: 33367271
DOI: 10.1016/j.xplc.2020.100118 -
Journal of Applied Physiology... Nov 2017High altitudes (>8,000 ft or 2,500 m) provide an experiment of nature for measuring adaptation and the physiological processes involved. Studies conducted over the past... (Review)
Review
High altitudes (>8,000 ft or 2,500 m) provide an experiment of nature for measuring adaptation and the physiological processes involved. Studies conducted over the past ~25 years in Andeans, Tibetans, and, less often, Ethiopians show varied but distinct O transport traits from those of acclimatized newcomers, providing indirect evidence for genetic adaptation to high altitude. Short-term (acclimatization, developmental) and long-term (genetic) responses to high altitude exhibit a temporal gradient such that, although all influence O content, the latter also improve O delivery and metabolism. Much has been learned concerning the underlying physiological processes, but additional studies are needed on the regulation of blood flow and O utilization. Direct evidence of genetic adaptation comes from single-nucleotide polymorphism (SNP)-based genome scans and whole genome sequencing studies that have identified gene regions acted upon by natural selection. Efforts have begun to understand the connections between the two with Andean studies on the genetic factors raising uterine blood flow, fetal growth, and susceptibility to Chronic Mountain Sickness and Tibetan studies on genes serving to lower hemoglobin and pulmonary arterial pressure. Critical for future studies will be the selection of phenotypes with demonstrable effects on reproductive success, the calculation of actual fitness costs, and greater inclusion of women among the subjects being studied. The well-characterized nature of the O transport system, the presence of multiple long-resident populations, and relevance for understanding hypoxic disorders in all persons underscore the importance of understanding how evolutionary adaptation to high altitude has occurred. Variation in O transport characteristics among Andean, Tibetan, and, when available, Ethiopian high-altitude residents supports the existence of genetic adaptations that improve the distribution of blood flow to vital organs and the efficiency of O utilization. Genome scans and whole genome sequencing studies implicate a broad range of gene regions. Future studies are needed using phenotypes of clear relevance for reproductive success for determining the mechanisms by which naturally selected genes are acting.
Topics: Acclimatization; Altitude; Arterial Pressure; Ethiopia; Hemoglobins; Humans; Hypoxia; Oxygen; Phenotype; Polymorphism, Single Nucleotide; Selection, Genetic; South America; Tibet
PubMed: 28860167
DOI: 10.1152/japplphysiol.00321.2017 -
Frontiers in Bioscience (Scholar... Jun 2011A review of the various approaches in understanding outdoor thermal comfort is presented. The emphasis on field surveys from around the world, particularly across... (Comparative Study)
Comparative Study Review
A review of the various approaches in understanding outdoor thermal comfort is presented. The emphasis on field surveys from around the world, particularly across Europe, enables us to understand thermal perception and evaluate outdoor thermal comfort conditions. The consistent low correlations between objective microclimatic variables, subjective thermal sensation and comfort outdoors, internationally, suggest that thermophysiology alone does not adequate describe these relationships. Focusing on the concept of adaptation, it tries to explain how this influences outdoor comfort, enabling us to inhabit and get satisfaction from outdoor spaces throughout the year. Beyond acclimatization and behavioral adaptation, through adjustments in clothing and changes to the metabolic heat, psychological adaptation plays a critical role to ensure thermal comfort and satisfaction with the outdoor environment. Such parameters include recent experiences and expectations; personal choice and perceived control, more important than whether that control is actually exercised; and the need for positive environmental stimulation suggesting that thermal neutrality is not a pre-requisite for thermal comfort. Ultimately, enhancing environmental diversity can influence thermal perception and experience of open spaces.
Topics: Acclimatization; Adaptation, Psychological; Energy Metabolism; Environment; Europe; Humans; Protective Clothing; Temperature; Thermosensing
PubMed: 21622290
DOI: 10.2741/245 -
The Journal of Physiology Nov 2022Maturational differences exist in cardiopulmonary and cerebrovascular function at sea-level, but the impact of maturation on acclimatization responses to high altitude...
Maturational differences exist in cardiopulmonary and cerebrovascular function at sea-level, but the impact of maturation on acclimatization responses to high altitude is unknown. Ten children (9.8 ± 2.5 years) and 10 adults (34.7 ± 7.1 years) were assessed at sea-level (BL), 3000 m and twice over 4 days at 3800 m (B1, B4). Measurements included minute ventilation ( ), end-tidal partial pressures of oxygen ( ) and carbon dioxide, echocardiographic assessment of pulmonary artery systolic pressure (PASP) and stroke volume (SV) and ultrasound assessment of blood flow through the internal carotid and vertebral arteries was performed to calculate global cerebral blood flow (gCBF). At 3000 m, was increased from BL by 19.6 ± 19.1% (P = 0.031) in children, but not in adults (P = 0.835); SV was reduced in children (-11 ± 13%, P = 0.020) but not adults (P = 0.827), which was compensated for by a larger increase in heart rate in children (+26 beats min vs. +13 beats min , P = 0.019). Between B1 and B4, adults increased by 38.5 ± 34.7% (P = 0.006), while did not increase further in children. The rise in PASP was not different between groups; however, ∆PASP from BL was related to ∆ in adults (R = 0.288, P = 0.022), but not children. At BL, gCBF was 43% higher in children than adults (P = 0.017), and this difference was maintained at high altitude, with a similar pattern and magnitude of change in gCBF between groups (P = 0.845). Despite increasing in children but not adults at a lower altitude, the pulmonary vascular and cerebrovascular responses to prolonged hypoxia are similar between children and adults. KEY POINTS: Children have different ventilatory and metabolic requirements from adults, which may present differently in the pulmonary and cerebral vasculature upon ascent to high altitude. Children (ages 7-14) and adults (ages 23-44) were brought from sea level to high altitude (3000 to 3800 m) and changes in ventilation, pulmonary artery systolic pressure (PASP) and cerebral blood flow (CBF) were assessed over 1 week. Significant increases in ventilation and decreases in left ventricle stroke volume were observed at a lower altitude in children than adults. PASP and CBF increased by a similar relative amount between children and adults at 3800 m. These results help us better understand age-related differences in compensatory responses to prolonged hypoxia in children, despite similar changes in pulmonary artery pressure and CBF between children and adults.
Topics: Humans; Child; Adolescent; Young Adult; Adult; Blood Flow Velocity; Acclimatization; Altitude; Cerebrovascular Circulation; Hypoxia
PubMed: 36165275
DOI: 10.1113/JP283419 -
Molecular Aspects of Medicine Apr 2022In mammals and other air-breathing vertebrates that live at high altitude, adjustments in convective O transport via changes in blood hemoglobin (Hb) content and/or Hb-O... (Review)
Review
In mammals and other air-breathing vertebrates that live at high altitude, adjustments in convective O transport via changes in blood hemoglobin (Hb) content and/or Hb-O affinity can potentially mitigate the effects of arterial hypoxemia. However, there are conflicting views about the optimal values of such traits in hypoxia, partly due to the intriguing observation that hypoxia-induced acclimatization responses in humans and other predominantly lowland mammals are frequently not aligned in the same direction as evolved phenotypic changes in high-altitude natives. Here we review relevant theoretical and empirical results and we highlight experimental studies of rodents and humans that provide insights into the combination of hematological changes that help attenuate the decline in aerobic performance in hypoxia. For a given severity of hypoxia, experimental results suggest that optimal values for hematological traits are conditional on the states of other interrelated phenotypes that govern different steps in the O-transport pathway.
Topics: Acclimatization; Altitude; Animals; Hemoglobins; Humans; Hypoxia; Oxygen; Oxygen Consumption
PubMed: 34879970
DOI: 10.1016/j.mam.2021.101052 -
Animal Models and Experimental Medicine Dec 2021Oxygen plays a pivotal role in the metabolism and activities of mammals. However, oxygen is restricted in some environments-subterranean burrow systems or habitats at... (Review)
Review
Oxygen plays a pivotal role in the metabolism and activities of mammals. However, oxygen is restricted in some environments-subterranean burrow systems or habitats at high altitude or deep in the ocean-and this could exert hypoxic stresses such as oxidative damage on organisms living in these environments. In order to cope with these stresses, organisms have evolved specific strategies to adapt to hypoxia, including changes in physiology, gene expression regulation, and genetic mutations. Here, we review how mammals have adapted to the three high-altitude plateaus of the world, the limited oxygen dissolved in deep water habitats, and underground tunnels, with the aim of better understanding the adaptation of mammals to hypoxia.
Topics: Acclimatization; Adaptation, Physiological; Altitude; Animals; Hypoxia; Mammals
PubMed: 34977482
DOI: 10.1002/ame2.12189 -
Journal of Applied Physiology... Mar 2016Studying "phenotypic plasticity" involves comparison of traits expressed in response to environmental fluctuations and aims to understand tolerance and survival in new... (Review)
Review
Studying "phenotypic plasticity" involves comparison of traits expressed in response to environmental fluctuations and aims to understand tolerance and survival in new settings. Reversible phenotypic changes that enable individuals to match their phenotype to environmental demands throughout life can be artificially induced, i.e., acclimation or occur naturally, i.e., acclimatization. The onset and achievement of acclimatory homeostasis are determined by molecular programs that induce the acclimated transcriptome. In heat acclimation, much evidence suggests that epigenetic mechanisms are powerful players in these processes. Epigenetic mechanisms affect the accessibility of the DNA to transcription factors, thereby regulating gene expression and controlling the phenotype. The heat-acclimated phenotype confers cytoprotection against novel stressors via cross-tolerance mechanisms, by attenuation of the initial damage and/or by accelerating spontaneous recovery through the release of help signals. This indispensable acclimatory feature has a memory and can be rapidly reestablished after the loss of acclimation and the return to the physiological preacclimated phenotype. The transcriptional landscape of the deacclimated phenotype includes constitutive transcriptional activation of epigenetic bookmarks. Heat shock protein (HSP) 70/HSP90/heat shock factor 1 memory protocol demonstrated constitutive histone H4 acetylation on hsp70 and hsp90 promotors. Novel players in the heat acclimation setup are poly(ADP-ribose)ribose polymerase 1 affecting chromatin condensation, DNA linker histones from the histone H1 cluster, and transcription factors associated with the P38 pathway. We suggest that these orchestrated responses maintain euchromatin and proteostasis during deacclimation and predispose to rapid reacclimation and cytoprotection. These mechanisms represent within-life epigenetic adaptations and cytoprotective memory.
Topics: Acclimatization; Animals; Cytoprotection; Epigenesis, Genetic; Heat-Shock Proteins; Hot Temperature; Humans; Transcription Factors; Transcriptional Activation; Transcriptome
PubMed: 26472869
DOI: 10.1152/japplphysiol.00552.2015