Why do Some Muscles Show Fewer Signs of Aging?

Not all muscles in the body age equally, it seems, and those surrounding the eye are spared many of the degenerative changes that occur elsewhere. Investigating why this is the case may help to inform other lines of research that aim to revert the characteristic age-related decline in stem cell activity, and thereby restore function to increasingly frail tissues. At present groups working on reversal of stem cell aging are largely focused on the stem cell populations associated with muscles, such as satellite cells, as this is where many of the early relevant discoveries occurred, the tissues are easily accessible, and these cell types are fairly well understood and comparatively easy to work with.

Specific muscles are spared in many degenerative myopathies. Most notably, the extraocular muscles (EOMs) do not show clinical signs of late stage myopathies including the accumulation of fibrosis and fat. It has been proposed that an altered stem cell niche underlies the resistance of EOMs in these pathologies, however, to date, no reports have provided a detailed characterization of the EOM stem cell niche.

PW1/Peg3 is expressed in progenitor cells in all adult tissues including satellite cells and a subset of interstitial non-satellite cell progenitors in muscle. These PW1-positive interstitial cells (PICs) include a fibroadipogenic progenitor population (FAP) that give rise to fat and fibrosis in late stage myopathies. PICs/FAPs are mobilized following injury and FAPs exert a promyogenic role upon myoblasts in vitro but require the presence of a minimal population of satellite cells in vivo. We and others recently described that FAPs express promyogenic factors while satellite cells express antimyogenic factors suggesting that PICs/FAPs act as support niche cells in skeletal muscle through paracrine interactions.

We analyzed the EOM stem cell niche in young adult and aged wild-type mice and found that the balance between PICs and satellite cells within the EOM stem cell niche is maintained throughout life. Moreover, in the adult mdx mouse model for Duchenne muscular dystrophy (DMD), the EOM stem cell niche is unperturbed compared to normal mice, in contrast to Tibialis Anterior (TA) muscle, which displays signs of ongoing degeneration/regeneration. Regenerating mdx TA shows increased levels of both PICs and satellite cells, comparable to normal unaffected EOMs. We propose that the increase in PICs that we observe in normal EOMs contributes to preserving the integrity of the myofibers and satellite cells. Our data suggest that molecular cues regulating muscle regeneration are intrinsic properties of EOMs.

Link: http://dx.doi.org/10.3389/fnagi.2014.00328

Comments

Now that's interesting lead.

It's so obvious, too obvious probably, that some muscles age very differently: why did my grandparents experience such difficulties to move, but could still move their eyelids naturally?

I hope the investigation will go further.

Posted by: Nico at December 19th, 2014 8:49 AM

Does anyone have any thoughts regarding the evolution of the different types of muscle cells, specifically the EOMs? I mean, different muscle cell lines have evolved to meet specific needs e.g. heart muscle cells must beat rhythmically and without rest but never (I think) anaerobically (I could be wrong), whereas skeletal muscle muscles can rest but must be able to function anaerobically at times.

Posted by: Ben at December 19th, 2014 11:47 AM

Interestingly, control of extraocular muscles is also usually spared in ALS. ALS is generally understood to be a disease of motor neurons, not of muscle fibers, so unless this is just a coincidence, it may say something interesting either about ALS (more involvement of the muscle itself than believed) or normal muscle aging (more involvement of motor neurons than believed).

Posted by: Brandon Berg at December 19th, 2014 5:01 PM

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