Cells and Aging

James james at ryley.com
Wed Mar 10 20:42:07 EST 1999

Thomas Mahoney wrote:


> The musculature loss noted could very well be related to any number of the
> factors you noted as well as loss of nerve function or denervation.
> Telomeric shortening would only apply to the satellite cells which would be
> stressed to the point of replicative in-capacity trying to restore the muscle
> cells lost for whatever reason.
> This position is supported by Dr. Decarys' work previously cited and in the
> paper; J Neurobiol 1992 Jun;23(4):407-19, "Transient neonatal denervation
> alters the proliferative capacity of myosatellite cells in dystrophic
> (129ReJdy/dy) muscle.", Ontell MP, et al, (Work done at my alma matter, The
> Univ. of Pittsburgh).
> The research most on point is; (Somat Cell Mol Genet 1990Nov;16(6):557-65
> "Accelerated age-related decline in replicative life-span of Duchenne
> muscular dystrophy myoblasts: implications for cell and gene therapy.",
> Webster C, Blau HM), where they say "Our results suggest that the myoblasts
> (satellite cells) of even the youngest DMD patients have undergone extensive
> division in an attempt to regenerate degenerating myofibers." and "A decline
> in replicative capacity was observed with increasing donor age, which was
> markedly accelerated for DMD, (Duchenne muscular dystrophy).
> To restate my position, based on the research cited, the loss of musculature
> in the elderly is, most likely, unrelated to telomeric loss or replicative
> senescence, but the satellite cells ability to restore lost muscle cells is
> compromised by telomeric loss leading to replicative senescence.

You are not addressing the issue.  Once again, I am not saying
that there is no decrease in replicative capacity, either in old
age, or in disease.  Let's assume that age, DMD, FSHD, BMD, and
every other dystrophy in the world, cause telomeric shortening. 
Fine.  Now we have a CORRELATION.  We DO NOT have cause and
effect.  The correlation says that satellite cells exhibit
reduced replicative capacity when they have to divide over and
over again -- whatever the cause (disease or old age).  That
sounds reasonable enough.

But the question is: So what?  Is it biologically relevant?  Can
you provide me with any evidence at all that there is more than
correlation at work here?  Any evidence that the AMOUNT of
reduction in replicative capacity is sufficient to cause muscle
wasting in old age?

I have provided what I think is a decent argument for why is is
NOT anything more than a correlation:  Namely that the satellite
cells must have a huge proliferative reserve capacity for people
with various dystrophies to survive to old age.  Therefore, the
decrease in replicative capacity during normal old age, however
statistically real it may be, is not biologically significant,
because in the absence of disease, no one would ever approach the
point of using up all of their potential divisions.

Let me put it in simpler terms (I mean no insult by that, but I
fear that I am not getting my point across):

If people with muscular dystrophy can survive to old age with
relatively intact muscle, after decades of muscle death and
regeneration, how can it be that a healthy old person is anywhere
NEAR the end of their satellite cell replicative potential?  

Nothing you have cited addresses that question.


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