f You Can't Take the Height, Get Off the Mountain

Taking a breather.
Himalayan subjects suck in oxygen as part of the study.

Credit: Otto Appenzeller

By Andrea Lu

Life at high altitudes isn't easy. The thin mountain air can cause a slew of health problems, even for people who have lived at elevation for centuries. Some groups fare better than others, however, and researchers now think they've found one reason: varying expression levels of a gene called PDP2, which codes for a protein that helps transform food to fuel.

Many groups have adapted to low oxygen levels at high altitudes by boosting their production of red blood cells, which carry oxygen to the body's tissues. The strategy comes at a cost: All of those cells can thicken the blood and impede its flow, leading to headaches, fatigue, insomnia, and memory impairment. Susceptibility to the condition, known as chronic mountain sickness (CMS), varies among populations. A team of researchers led by neuroscientist Otto Appenzeller of the New Mexico Health Enhancement and Marathon Clinics Research Foundation wanted to find out why.

The researchers focused on three groups: East African highlanders, who dwell on the Ethiopian plateau 3600 meters above sea level; Peruvians of the Andes, who live at 4300 meters; and Himalayans who live on the Tibetan plateau at 4500 meters. Ethiopian highlanders rarely show signs of CMS; the disorder appears more frequently in the Tibetans and even more frequently in the Andeans. Scientists suspect that the difference may be evolutionary: The Ethiopians and the Tibetans ascended their respective mountains earlier than their Andean peers, giving them a head start in adapting to life up high.

The team focused on a handful of genes, all of which had been implicated in adaptation to low-oxygen environments. For each region, the researchers compared gene expression levels in white blood cells, which respond quickly to changes in oxygen levels, in high-altitude subjects with CMS with those without the disease.

Of the three groups, Ethiopians displayed the highest expression levels of the oxygen-adaptation genes, followed by Tibetans and then Andeans. One of these genes, PDP2, linked strongly to CMS. Individuals with CMS had significantly lower PDP2 expression than those without the condition, regardless of ethnic group, suggesting that the gene helps individuals acclimatize to poor oxygen levels. That matches up well to the incidence of CMS observed in these populations, says author and molecular biologist Guo-Qiang Xing of the Uniformed Services University of the Health Sciences in Bethesda, Maryland.

The researchers believe that PDP2 helps people adjust to poor oxygen levels by promoting aerobic cellular respiration. This metabolic pathway uses oxygen to covert glucose to cellular energy and thus obviates the need to make more red blood cells.

The finding might eventually help people who dwell at sea level. The inability of cells to access oxygen has been linked to multiple diseases including cancer, asthma, and Alzheimer's. Any connection between these conditions and PDP2 is speculative, Appenzeller admits, but he believes that "we can learn from this experiment of nature" in the mountains.

Robert Roach, a physiologist at the Altitude Research Center at the University of Colorado Denver School of Medicine in Aurora, calls the research a "fantastic preliminary study." He believes that it will inspire many follow-up studies, which he says "could reveal tremendous insights on how humans adapt to a changing environment."

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