SAN FRANCISCO — If you want the secret to a healthier life, it might be a move to the mountains. A new study finds the two million people who live at an elevation of more than 4,500 meters — about the height of Mount Rainier, Mount Whitney, and many Colorado and Alaska peaks — appear to have lower rates of metabolic diseases such as diabetes and coronary heart disease.
The new animal study suggests it’s not just the daily treks up the mountains that leave them in tip-top shape. Researchers in California say the reason behind their good health stems from the low oxygen levels from living at higher elevations. Understanding how low oxygen levels affect health could lead to some new strategies for treating metabolic diseases.
“When an organism is exposed to chronically low levels of oxygen, we found that different organs reshuffle their fuel sources and their energy-producing pathways in various ways,” says study senior author Isha Jain, PhD, a Gladstone assistant investigator, in a statement. “We hope these findings will help us identify metabolic switches that might be beneficial for metabolism even outside of low-oxygen environments.”
At sea level, oxygen makes up 21 percent of the air. For those living above 4,500 meters (14,764 feet), however, oxygen makes up only 11 percent of the air. Living in these areas for long periods of time forces the human body to adapt to the shortage of oxygen — otherwise known as hypoxia.
Could less oxygen actually be good for you?
Hypoxia is an area of interest for biologists who have observed it among isolated cells or within cancerous tumors. In the current study, Jain and her colleagues looked at how long-term hypoxia impacts organs all over the body.
“We wanted to profile the metabolic changes that take place as an organism adapts to hypoxia,” says Ayush Midha, a graduate student in Jain’s lab and lead author of the study. “We thought this might provide some insight into how that adaptation protects against metabolic disease.”
The team placed adult mice in pressure chambers that contained 21, 11, or 8-percent oxygen — all levels where both mice and humans can survive. The researchers observed the rodent’s behavior over a three-week period along with keeping track of their temperature, carbon dioxide level, and blood sugar levels. PET scans helped the team look at how different organs were consuming nutrients.
It took a couple of days for the mice to adjust to the pressure chamber. Mice under conditions of hypoxia (11% and 8% oxygen levels) moved around less and sometimes spent hours staying completely still. However, by the end of the third week, their movement patterns returned to normal. Carbon dioxide levels in the blood decreased when mice breathe faster to get more oxygen, but this returned to normal levels after the three-week period.
There was one bodily change that did not revert back to normal levels. The mice’s metabolism appeared permanently altered from the hypoxic chambers. Animals experiencing hypoxia had lower blood sugar levels and weight that never returned to pre-hypoxic levels. The researchers suggest these long-term changes resemble what doctors see in people living in higher elevations.
This could be big news for diabetics
The PET scans of each organ showed some permanent changes as well. Normally, the body needs tons of oxygen to metabolize fatty acids (the building blocks of fats) and amino acids (the building blocks of protein). Less oxygen is necessary to metabolize sugar. Mice under hypoxic conditions showed an increase in glucose metabolism, an observation the researchers expected. The unexpected finding was that brown fat and skeletal muscles — two organs known for their high levels of glucose metabolism — reduced the amount of sugar they normally use.
“Prior to this study, the assumption in the field was that in hypoxic conditions, your whole body’s metabolism becomes more efficient in using oxygen, which means it burns more glucose and fewer fatty acids and amino acids,” says Jain. “We showed that while some organs are indeed consuming more glucose, others become glucose savers instead.”
Jain says the observation makes sense. Individual cells in a petri dish don’t need to compromise their glucose use. An entire animal, on the other hand, need to find ways to ration their glucose and make it last for all bodily systems.
The drop in glucose levels and body weight seen in hypoxic mice have a link to a lower risk of diseases in humans, including heart disease. Jain and her team hope to take these results and apply them on a cellular level. Their next work involves using hypoxic conditions to study individual cell types and levels of signaling molecules. The finding is a step towards creating new drugs that mimic the metabolic benefits hypoxia or high-altitude trips provide to human health.
“We already see athletes going to train at altitude to improve their athletic performance; maybe in the future, we’ll start recommending that people spend time at high altitude for other health reasons,” concludes Midha.
The study is published in the journal Cell Metabolism.