Comparing integrative ventilatory and renal acid-base acclimatization in lowlanders and Tibetan highlanders during ascent to 4,300 m.

With over 14 million people living above 3,500 m, the study of acclimatization and adaptation to high altitude in human populations is of increasing importance, where exposure to high altitude (HA) imposes a blood oxygenation and acid-base challenge. A sustained and augmented hypoxic ventilatory response protects oxygenation through ventilatory acclimatization, but elicits hypocapnia and respiratory alkalosis. A subsequent renally mediated compensatory metabolic acidosis corrects pH toward baseline values, with a high degree of interindividual variability.

Larger spleens and greater splenic contraction during exercise may be an adaptive characteristic of Nepali Sherpa at high-altitude.

Objectives: The Sherpa ethnic group living at altitude in Nepal may have experienced natural selection in response to chronic hypoxia. We have previously shown that Sherpa in Kathmandu (1400 m) possess larger spleens and a greater apnea-induced splenic contraction compared to lowland Nepalis. This may be significant for exercise capacity at altitude as the human spleen responds to stress-induced catecholamine secretion by an immediate contraction, which results in transiently elevated hemoglobin concentration ([Hb]).

Differential splenic responses to hyperoxic breathing at high altitude in Sherpa and lowlanders.

The human spleen contracts in response to stress-induced catecholamine secretion, resulting in a temporary rise in haemoglobin concentration ([Hb]). Recent findings highlighted enhanced splenic response to exercise at high altitude in Sherpa, possibly due to a blunted splenic response to hypoxia. To explore the potential blunted splenic contraction in Sherpas at high altitude, we examined changes in spleen volume during hyperoxic breathing, comparing acclimatized Sherpa with acclimatized individuals of lowland ancestry.

High-Altitude Andean H194R HIF2A Allele Is a Hypomorphic Allele.

For over 10,000 years, Andeans have resided at high altitude where the partial pressure of oxygen challenges human survival. Recent studies have provided evidence for positive selection acting in Andeans on the HIF2A (also known as EPAS1) locus, which encodes for a central transcription factor of the hypoxia-inducible factor pathway. However, the precise mechanism by which this allele might lead to altitude-adaptive phenotypes, if any, is unknown.

Comparing high versus low-altitude populations to test human adaptations for increased ventilation during sustained aerobic activity.

Despite aerobic activity requiring up to tenfold increases in air intake, human populations in high-altitude hypoxic environments can sustain high levels of endurance physical activity. While these populations generally have relatively larger chest and lung volumes, how thoracic motions actively increase ventilation is unknown. Here we show that rib movements, in conjunction with chest shape, contribute to ventilation by assessing how adulthood acclimatization, developmental adaptation, and population-level adaptation to high-altitude affect sustained aerobic activity.

Size at birth and accelerometer-measured physical activity or sedentary behavior in healthy term-born adults.

The present study investigated the relationship between birth size and activity patterns. One hundred and twenty-four adults wore accelerometers for 7 days. Birth weight was adjusted for gestational age (AdjBW).

Intra-uterine effects on adult muscle strength.

Background: Maternal behaviors and exposures affect fetal growth and development. Smoking, malnutrition, sedentary behavior, and stress can each lead to fetal programming and intra-uterine growth restriction. As a result, tissue development may be impaired.

Genome-Wide DNA Methylation Changes Associated With High-Altitude Acclimatization During an Everest Base Camp Trek.

The individual physiological response to high-altitude hypoxia involves both genetic and non-genetic factors, including epigenetic modifications. Epigenetic changes in hypoxia factor pathway (HIF) genes are associated with high-altitude acclimatization. However, genome-wide epigenetic changes that are associated with short-term hypoxia exposure remain largely unknown.

Blood lead levels in Peruvian adults are associated with proximity to mining and DNA methylation.

Background: Inorganic lead (Pb) is common in the environment, and is toxic to neurological, renal, and cardiovascular systems. Pb exposure influences the epigenome with documented effects on DNA methylation (DNAm). We assessed the impact of low levels of Pb exposure on DNAm among non-miner individuals from two locations in Peru: Lima, the capital, and Cerro de Pasco, a highland mining town, to study the effects of Pb exposure on physiological outcomes and DNAm.

Genome-Wide Epigenetic Signatures of Adaptive Developmental Plasticity in the Andes.

High-altitude adaptation is a classic example of natural selection operating on the human genome. Physiological and genetic adaptations have been documented in populations with a history of living at high altitude. However, the role of epigenetic gene regulation, including DNA methylation, in high-altitude adaptation is not well understood.

The effects of high altitude ascent on splenic contraction and the diving response during voluntary apnoea.

New Findings: What is the central question of this study? What is the relative contribution of a putative tonic splenic contraction to the haematological acclimatization process during high altitude ascent in native lowlanders? What is the main finding and its importance? Spleen volume decreased by -14.3% (-15.2 ml) per 1000 m ascent, with an attenuated apnoea-induced [Hb] increase, attesting to a tonic splenic contraction during high altitude ascent.

Cardiorespiratory hysteresis during incremental high-altitude ascent-descent quantifies the magnitude of ventilatory acclimatization.

New Findings: What is the central question of this study? We assessed the utility of a new metric for quantifying ventilatory acclimatization to high altitude, derived from differential ascent and descent steady-state cardiorespiratory variables (i.e. hysteresis).

Preservation of Neurovascular Coupling to Cognitive Activity in Anterior Cerebrovasculature During Incremental Ascent to High Altitude.

High altitude sojourn challenges blood flow regulation in the brain, which may contribute to cognitive dysfunction. Neurovascular coupling (NVC) describes the ability to increase blood flow to working regions of the brain. Effects of high altitude on NVC in frontal regions undergoing cognitive activation are unclear but may be relevant to executive function in high-altitude hypoxia.

DNA Methylation Changes Are Associated With an Incremental Ascent to High Altitude.

Genetic and nongenetic factors are involved in the individual ability to physiologically acclimatize to high-altitude hypoxia through processes that include increased heart rate and ventilation. High-altitude acclimatization is thought to have a genetic component, yet it is unclear if other factors, such as epigenetic gene regulation, are involved in acclimatization to high-altitude hypoxia in nonacclimatized individuals. We collected saliva samples from a group of healthy adults of European ancestry (n = 21) in Kathmandu (1,400 m; baseline) and three altitudes during a trek to the Everest Base Camp: Namche (3,440 m; day 3), Pheriche (4,240 m; day 7), and Gorak Shep (5,160 m; day 10).

Association of gene with high aerobic capacity of Peruvian Quechua at high altitude.

Highland native Andeans have resided at altitude for millennia. They display high aerobic capacity (VOmax) at altitude, which may be a reflection of genetic adaptation to hypoxia. Previous genomewide (GW) scans for natural selection have nominated gene () as a candidate gene.

Steady-state cerebral blood flow regulation at altitude: interaction between oxygen and carbon dioxide.

High-altitude ascent imposes a unique cerebrovascular challenge due to two opposing blood gas chemostimuli. Specifically, hypoxia causes cerebral vasodilation, whereas respiratory-induced hypocapnia causes vasoconstriction. The conflicting nature of these two superimposed chemostimuli presents a challenge in quantifying cerebrovascular reactivity (CVR) in chronic hypoxia.

Exhaled nitric oxide in ethnically diverse high-altitude native populations: A comparative study.

Objectives: Andean and Tibetan high-altitude natives exhibit a high concentration of nitric oxide (NO) in the lungs, suggesting that NO plays an adaptive role in offsetting hypobaric hypoxia. We examined the exhaled NO concentration as well as partial pressure of several additional high-altitude native populations in order to examine the possibility that this putative adaptive trait, that is, high exhaled NO, is universal.

Methods: We recruited two geographically diverse highland native populations, Tawang Monpa (TM), a Tibetan derived population in North-Eastern India (n = 95, sampled at an altitude of ~3,200 m), and Peruvian Quechua from the highland Andes (n = 412).

Effects of Prolonged Dietary Curcumin Exposure on Skeletal Muscle Biochemical and Functional Responses of Aged Male Rats.

Oxidative stress resulting from decreased antioxidant protection and increased reactive oxygen and nitrogen species (RONS) production may contribute to muscle mass loss and dysfunction during aging. Curcumin is a phenolic compound shown to upregulate antioxidant defenses and directly quench RONS in vivo. This study determined the impact of prolonged dietary curcumin exposure on muscle mass and function of aged rats.

Transthoracic sonographic assessment of B-line scores during ascent to altitude among healthy trekkers.

Sonographic B-lines can indicate pulmonary interstitial edema. We sought to determine the incidence of subclinical pulmonary edema measured by sonographic B-lines among lowland trekkers ascending to high altitude in the Nepal Himalaya. Twenty healthy trekkers underwent portable sonographic examinations and arterial blood draws during ascent to 5160 m over ten days.

Changes in cognitive function and latent processes of decision-making during incremental ascent to high altitude.

High altitude sojourn is broadly associated with impaired cognitive function, although there are inconsistencies within the literature. Incorporation of mathematical modeling to gain insight into latent aspects of decision-making may strengthen the ability to characterize changes in cognitive function during high altitude sojourn. This study sought to examine the effects of high altitude on cognitive function and underlying constructs of decision-making during an 11-d incremental ascent to 5160 m in 18 healthy adults (26 ± 12 yrs).

LINE-1 and EPAS1 DNA methylation associations with high-altitude exposure.

Recent discoveries indicate a genetic basis for high-altitude adaptation among human groups who have resided at high altitude for millennia, including Andeans, Tibetans, and Ethiopians. Yet, genetics alone does not explain the extent of variation in altitude-adaptive phenotypes. Current and past environments may also play a role, and one way to determine the effect of the environment is through the epigenome.

Neurovascular Coupling Remains Intact During Incremental Ascent to High Altitude (4240 m) in Acclimatized Healthy Volunteers.

Neurovascular coupling (NVC) is the temporal link between neuronal metabolic activity and regional cerebral blood flow (CBF), supporting adequate delivery of nutrients. Exposure to high altitude (HA) imposes several stressors, including hypoxia and hypocapnia, which modulate cerebrovascular tone in an antagonistic fashion. Whether these contrasting stressors and subsequent adaptations affect NVC during incremental ascent to HA is unclear.

Renal reactivity: acid-base compensation during incremental ascent to high altitude.

Key Points: Ascent to high altitude imposes an acid-base challenge in which renal compensation is integral for maintaining pH homeostasis, facilitating acclimatization and helping prevent mountain sicknesses. The time-course and extent of plasticity of this important renal response during incremental ascent to altitude is unclear. We created a novel index that accurately quantifies renal acid-base compensation, which may have laboratory, fieldwork and clinical applications.

Can an automated sleep detection algorithm for waist-worn accelerometry replace sleep logs?

The purpose of this study was to test whether estimates of bedtime, wake time, and sleep period time (SPT) were comparable between an automated algorithm (ALG) applied to waist-worn accelerometry data and a sleep log (LOG) in an adult sample. A total of 104 participants were asked to log evening bedtime and morning wake time and wear an ActiGraph wGT3X-BT accelerometer at their waist for 24 h/day for 7 consecutive days. Mean difference and mean absolute difference (MAD) were computed.