Preventing age-related muscle loss

One of the most devastating but least-discussed aspects of age-related decline is the onset of frailty, i.e., the progressive loss of robustness in multiple tissues and organ systems. Because frailty comes eventually to every aging person (if they’re lucky enough to live that long), it’s lumped into the category of “normal aging”; possibly as a result, relatively little attention is paid to causes and potential treatments.

Fortunately, this is starting to change, as exemplified by this recent paper from Siriett et al.. The authors address the role of myostatin in sarcopenia, the gradual loss of muscle mass and strength that accompanies advanced aging:

… Myostatin, a negative regulator of pre- and postnatal myogenesis, inhibits satellite cell activation and muscle regeneration postnatally. To investigate the role of myostatin during age-related sarcopenia, we examined muscle mass and regeneration in young and old myostatin-null mice. Young myostatin-null muscle fibers were characterized by massive hypertrophy and hyperplasia and an increase in type IIB fibers, resulting in a more glycolytic muscle. With ageing, wild-type muscle became increasingly oxidative and fiber atrophy was prominent. In contrast no fiber type switching was observed and atrophy was minimal in aged myostatin-null muscle. The effect of ageing on satellite cell numbers appeared minimal, however, satellite cell activation declined significantly in both wild-type and myostatin-null muscles. In young mice, lack of myostatin resulted in increased satellite cell number and activation compared to wild-type, suggesting a greater propensity to undergo myogenesis, a difference maintained in the aged mice. … In conclusion, a lack of myostatin appears to reduce age-related sarcopenia and loss of muscle regenerative capacity.

The experimental system was a full knockout (null), and it remains to be seen whether myostatin function can be present in early life (allowing for normal muscle development; the myostatin-null mice are muscle-bound and look a little ridiculous) but diminished late in life to reap the benefits of avoiding sarcopenia. An answer will have to wait the design of a conditional-knockout model, which is likely already in the works.


  1. So myostatin works mainly on fast white glycolitic fibers or on red ones, is there a preference? And what could be the connection of any myostatin fiber preference to satellite cell activation?

  2. Anyway, for frailty striatal muscle is an optimal model system, I am just now working on an article draft on a similar topic, it would be terrific to share the information with you, but sorrily we do not live in a Scientifically Open Source World. Yet. 🙂

  3. If you want to prevent muscle loss due to aging, you’re making this way too complicated here.

    I was diagnosed with Lyme Disease and watched my muscle mass disappear in fast forward. It still isn’t ‘right’ as I started going autoimmune and developed anti-striatal muscle antibodies.

    Lyme and coinfections are EPIDEMIC. Join the Lyme forum to find out what the CDC is concealing while people are told they have ‘MS’ (some for decades) or a host of other related incurable diseases.

    The cure for muscle loss, aging, and even death? ‘Science’ needs to kill all the parasites they took part in creating by making our bodies ideal hosts for such microscopic organisms, yet powerless to fight them off in our poisoned environment.

    Sorry – I just learned this year not to put any faith at all in science. Science is way behind. We’re all dying of parasites, and science is too busy trying to come up with names for a new cluster of symptoms, rather than curing us of our parasitic infections.

  4. A question still to be resolved is whether a murine model is adequately representational for myostatin and human skeletal muscle. One previous study showed differences in circulating bioactive and bound myostatin in humans versus murine (sign. lower levels in humans). Also, except for the rare case(s) of genetic myostatin deficiency, conclusive causative evidence lacks directly associating myostatin and muscle loss or growth.

  5. “Also, except for the rare case(s) of genetic myostatin deficiency, conclusive causative evidence lacks directly associating myostatin and muscle loss or growth.” Addendum: in adult humans.

  6. There is another way as well:
    Science Daily had a good article about this as well:

    “… adult muscle stem cells have a receptor called Notch, which triggers growth when activated. Those stem cells also have a receptor for the protein TGF-beta that, when excessively activated, sets off a chain reaction that ultimately inhibits a cell’s ability to divide.

    The researchers said that aging in mice is associated in part with the progressive decline of Notch and increased levels of TGF-beta, ultimately blocking the stem cells’ capacity to effectively rebuild the body.

    This study revealed that the same pathways are at play in human muscle, but also showed for the first time that mitogen-activated protein (MAP) kinase was an important positive regulator of Notch activity essential for human muscle repair, and that it was rendered inactive in old tissue.”

    Let me know what you think.

Comments are closed.