Muscling Through Hibernation

Artist's rendition of a grizzly bear

Russ Hodge, http://russhodge.wordpress.com/

Despite hibernating with little food or movement for five to seven months a year, grizzly bears (Ursus arctos horribilis) show little muscle atrophy. Research has linked this absence of atrophy to changes in gene expression, with potential applications for developing atrophy treatment for humans.

Cell biologist Michael Gotthardt and colleagues of the Max Delbrück Center for Molecular Medicine in Berlin and others from institutions in Germany and the United States sampled muscle cells before and during hibernation from four grizzlies at the Washington State University Bear Research Education and Conservation Center. The researchers used mass spectrometry to isolate the unique proteins active in grizzly muscle cells and RNA sequencing to trace these proteins’ origins back to around 200 genes, mostly involved in metabolism and cell signaling.

Examining the changes in proteins and modeling muscle cell metabolism in hibernating bears and aging humans led the team to identify six non-essential amino acids (NEAAs) that likely helped muscles maintain protein levels; levels of these six NEAAs were elevated in hibernating bears and lowered in aging humans’ muscles. When the researchers tested the NEAAs on isolated mice muscle cells, they found that the NEAAs boosted cell growth and decreased atrophy.

The researchers also compared protein-copying activity during bear hibernation with that of mice and humans experiencing muscle atrophy, such as from prolonged wearing of a plaster cast or from age or bed rest. Researchers tracked down overlapping genes regulating metabolism, cardiac activity, and growth. They found that knocking out some of these metabolic genes in nematode worms—a common laboratory model—led to nematodes shrinking in diameter, presumably from muscle atrophy. These results confirm the evolutionary connections among genes involved in regulating muscle size.

Gotthardt concluded that “the bear can make NEAAs from precursors in sufficient amounts so he does not have to break down protein to get them. The problem is that it is apparently important to make [NEAAs] or provide them locally.” Unfortunately, other research in humans has shown that simply administering the NEAAs in pill or powder form does not spur such effects. Still, the researchers believe that their findings could eventually lead to therapies to treat atrophy in human patients. (Scientific Reports)