Fight Aging!

The crafting of histrionic titles for research papers is a small artistic sideline in the research community. They catch the eye, and it's only human to have a little fun from time to time while working with important topics. The important topic in this case is stem cell aging, a decline in stem cell activity that leads to increasingly frail and dysfunctional tissue due to reduced maintenance activities. Much of the work on this topic presently focuses on muscle tissue and the associated stem cells known as satellite cells: researchers will probably produce a usefully complete model of the important aspects of the epigenetics and other biochemistry of aging in satellite cells before similar investigations draw to a close for any other population of cells.

In recent years it has become apparent that much of the decline in satellite cell activities is a response to the environment of aged tissue. If you take old satellite cells and put them into young tissue they go back to work as though youthful. Similarly there have been demonstrations in which researchers restore some of the youthful activities of old stem cells by reverting one or more differences in chemical signaling noted between young and old environments.

I see the existence of this sort of work as a positive sign for the future. We need the researchers of the large and very well funded stem cell research community to become more interested in reversing age-related degeneration of stem cells. It is a big project, and will require a great deal of work. Fortunately most of the prospective therapies that can be created through the fruits of stem cell research are aimed at the treatment of age-related conditions. In order for these therapies to be effective, researchers are somewhat forced into understanding why stem cells decline in old tissue, and find ways to at least temporarily stop this from happening.

At the present time it is somewhat ambiguous as to whether damage to stem cells or signaling and epigenetic responses to broader cellular damage in tissue are the major cause of stem cell aging in all populations. But I don't expect that ambiguity to persist for too much longer, not if the funding keeps ramping up for regenerative medicine, tissue engineering, and other outgrowths of the stem cell field. Let us return to the histrionics, however:

'From Death, Lead Me to Immortality' - Mantra of Ageing Skeletal Muscle

The relationship between satellite stem cell function and muscle regeneration and repair in ageing has yet to be rigorously addressed in mammals. Initial in vitro studies of satellite cells from young and old animals suggested that there was intrinsic ageing of this stem-cell population, as aged cells generated far fewer progeny. The finding that regeneration mediated by aged satellite cells was highly effective when the cells were transplanted into young animals as whole-muscle grafts suggest reversible modifications of aged muscle stem cells, an interpretation supported by recent data showing that aged muscle stem cells, when exposed to a youthful systemic milieu by virtue of parabiotic pairings of aged and young mice, activate and repair muscle nearly as well as young satellite cells. These modifications may be associated with intrinsic epigenetic changes within the satellite stem cell population supported by our studies in myoblast cellular ageing demonstrating increased methylation of the myogenin gene [that] reduced the capacity to form myotubes which was reversed by addition of methyltransferase inhibitor 5-azacytidine.

The coordinated control of DNA methylation by methyltransferases and chromatin states by histone modifiers will be a fascinating avenue for further investigation and will particularly benefit from genome-wide examination in young and old stem cell populations. As technologies for genomic analysis and sequencing continually improve profiling potential correlation between stem cell function and epigenetic changes become increasingly feasible. As the mechanisms underlying age dependent stem cell decline are better understood that leads to a decline in muscle function, studying the effects of manipulating satellite cell function on skeletal muscle maintenance over a organismal lifespan and healthspan will be an attainable goal - 'from death, lead me to immortality'.