December 05, 2003
Satellite Cells Can Be Stimulated To Repair Old Muscle More Rapidly

Satellite cells are a type of adult stem cells that can become myocytes, adipocytes or osteocytes. By becoming myocytes satellite cells help to repair injured muscle. Satellite cells do not divide as rapidly in older animals and as a result muscles do not heal as rapidly as humans and animals age. Some Stanford University School of Medicine researchers have discovered that a compound that mimicks the effect of a satellite cell regulatory protein can cause satellite cells to repair older muscles more rapidly.

In previous work, Rando found that satellite cells spring into action when a protein on the cell surface called Notch becomes activated, much like flicking the cell’s molecular “on” switch. What flips the switch is another protein called Delta, which is made on nearby cells in injured muscle. This same combination of Delta and Notch also plays a role in guiding cells through embryonic development.

Having found this pathway, Rando and Conboy wondered whether slow healing in older muscles resulted from problems with signaling between Delta and Notch – failing either to make enough Delta or to respond to the Delta signal.

In their initial experiments, Rando and Conboy found that young, middle-aged and older mice all had the same number of satellite cells in their muscles and that these cells contained equivalent amounts of Notch.

“It doesn’t seem as if there’s anything wrong with the satellite cells or Notch in aged muscle,” Rando said. That left Delta as the suspect molecule.

To test whether older muscles produce normal amounts of Delta, the researchers looked at the amount of protein made by mice of different ages. Young and adult mice, equivalent to about 20- and 45-year-old humans, both had a large increase in Delta after an injury. Muscles in older mice, equivalent to a 70-year-old human, made much less Delta after an injury, giving a smaller cry for help to the satellite cells. In response, fewer satellite cells were activated to repair the muscle damage.

A further set of experiments showed that slow repair in older muscles can be overcome. When the team applied a molecule to young muscles that blocked Delta, those satellite cells failed to divide in response to damage. Conversely, when they applied a Delta-mimicking molecule to injured, older muscles, satellite cells began dividing much like the those in younger muscle. The older muscles with artificially activated satellite cells had a regenerative ability comparable to that of younger muscle.

Although the studies focused on muscle regeneration after injury, Rando said similar problems with the interplay between Delta and Notch may cause the gradual muscle atrophy that occurs in older people, in astronauts or in people whose limbs are immobilized in a cast or from bed rest.

There might be cancer risks from taking a Delta-mimicking drug as a long-term treatment to avoid the muscle atrophy that comes with age. It is likely that the satellite cells really are aging and the down-regulation of Delta might be an evolutionary adaptation to reduce the risk that mutated and damaged pre-cancerous satellite cells might be stimulated to divide and become cancerous. This result does not eliminate the need to develop cell therapies to replace satellite cells with more youthful replacements.

The other reason that lower Delta activity with age might have been selected for as an evolutionary adaptation is again age related: this might have been done to conserve the cells by reducing the number of times they divide. The satellite cells probably can divide only a limited number of times. By reducing the production of Delta with age the satellite cells might be conserved for higher priority uses. Upregulating Delta or delivering a Delta agonist might simply wear out the satellite cells too rapidly providing a short-term benefit but a longer term greater harm.

What is needed is a process that can easily isolate aged adult stem cells from one's own body and basically refurbish and rejuvenate them. It is not too hard to see the broad outlines of what such a rejuvenation process might look like. One step has got to be a way to sort through different stem cells isolated from the body to choose ones that have little damage to their chromosomes and, in particular, little or no damage to genes that regulate cell growth. An accumulation of mutations to genes that regulate cell growth is what produces cancers. Rejuvenation of stem cells that are close to becoming cancerous would pose a substantial health risk. Gene therapy applied to carefully selected adult stem cells would elongate their telomeres and perhaps do other rejuvenating repairs. Then the rejuvenated cells would be grown up in large numbers and reinjected back into various appropriate locations of the body that they were originally isolated from.

Share |      Randall Parker, 2003 December 05 10:05 AM  Aging Reversal

Bob Badour said at December 6, 2003 8:46 AM:

One would not have to stimulate satellite cells continuously to receive the benefit. One could stimulate satellite cells after surgery or trauma to reduce healing times, hospitalization etc. I am fairly certain the benefit during these short periods would outweigh the increased risk of cancer.

Lab Rat said at February 5, 2004 5:33 AM:

The question is, are there other means to increase the delta compond more for athletes through safe and legal means?

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