New clues about the biochemistry of aging muscle tissue

Researchers at the University of California, Berkley, have discovered new clues about what makes muscle less supple and regenerative in old age. The team identified low levels of mitogen-actived protein kinase (MAPK) as responsible for old muscle’s degradation and have been able to reverse these changes in tissue cultures by artificially activating MAPK.

In the first part of the study, the researchers wanted to study the physiological differences between old and young muscle tissue. 15 subjects aged 21-24 and 15 aged 68-74 were selected for the study. First, a muscle biopsy was taken from the quadriceps at the beginning of the study. Next, the subjects had their leg immobilized by a cast for two weeks in order to simulate muscle atrophy, and a second biopsy was taken. Finally, the two groups underwent four weeks of exercise training to regain muscle function, and a third biopsy was taken..

It was found that adult stem cell activity (necessary for muscle repair) was only half as much in the old subjects as the young subjects. Additionally, the old subjects experienced greater amounts of atrophy and did not reclaim much of their previous muscle mass. The first conclusion is that it is important for the elderly to stay active, for extended periods of muscle disuse may irreparably damage the muscle.

The team decided to look into the biochemistry of the muscle tissues to explore the mechanisms behind this degradation. Previous research has established that adult muscle stem cells have a “Notch” receptor that triggers growth - good. However the cells have another receptor for TGF-beta protein that starts a biochemical pathway that ultimately stops the cell’s division – not good. Aging in mice is associated with higher levels of TGF-beta.

The study discovered that mitogen-activated protein kinase (MAPK), an enzyme important for organ development, is a Notch regulator. The amount of MAPK in tissues from the old subjects was very low, so the Notch receptors on adult stem cells were not being activated, inhibiting the ability of the adult stem cells to repair the tissue. Interestingly, when the researchers artificially activated MAPK in a culture of old tissue, the regenerative ability of the old muscle was increased. Similarly, when they inactivatived MAPK in the young tissue, the tissue lost much of its regenerative ability.

The implication is that either the NOTCH or the MAPK pathways would make good therapeutic targets to combat muscle degradation in old age or degenerative muscle disorders.

I found this article interesting because it offers the first hints of an explanation of why muscles seem to "wear out" over time. The heart is a muscle, so perhaps a similar pathway governs the heart's gradual decline in old age. A few of my relatives have died because their hearts just "wore out," with blood flow and circulation slowly but inexorably dropping over the course of several years. This article provides an explanation for this phenomenon and offers hope that one day, maybe not within my lifetime, natural muscle atrophy will be reversible.