University of Basel: Muscle Aging Can Be Reversed With Rapamycin

As a person ages, body physiology and functionality changes. The muscle mass especially decreases and the number of morbidities increases. However, recent advances in the field of medicine have been successful in treating conditions like cardiovascular disease, diabetes, and cancer, the main life-threatening diseases that affect the elderly. But in the process of studying and treating these diseases, many other age-related changes and pathologies have been exposed.

Rapamycin

Rapamycin

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Sarcopenia, or age-related muscle disease, is one such pathology that has been brought to attention. It is characterized by loss of skeletal muscle mass and function and it severely affects the quality of life of an individual. Sarcopenia affects approximately 30% of the US population above the ages of 60 and 50% of the US population above the age of 80.

The disease severely constrains physical activity, even of the mildest form, hence affecting the autonomy and physical abilities of a person. It is important to note that even though aging is considered the main etiologic factor and it commonly presents itself in the elderly, the initiation process of the disease begins earlier on in life and can be affected by lack of physical activity and maintaining a sedentary life. Both of these can cause a person to develop sarcopenia later on in life.

Mechanism of Sarcopenia

The etiology of sarcopenia is mainly aging, however the molecular mechanisms behind the development of sarcopenia range from a change in the muscular innervation to altering of muscle metabolism.

A recent study conducted and led by Professor Markus Rüegg discovered that the suppression of mTORC1 can be used to treat sarcopenia. In literature, nine processes are hypothesized to be involved in the process of aging. All these processes meet the three criteria: 

  1. Happens during normal aging
  2. Augmentation of process speeds the process of aging
  3. The suppression of the process slows down aging.

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The protein complex, mTORC1 was found to be the central protein for the functioning of all nine biological processes, in all the studies. Due to this, Ruegg and his team decided to study and suppress this protein’s function with the aim of dampening the progression of sarcopenia.

The protein complex, mTORC1 controls protein synthesis and muscle mass. Overactivity of this complex is important for the development of muscle hypertrophy and complete blocking of it results in myopathy.

Ruegg and his team used the drug, rapamycin, in this study to suppress the protein complex, mTORC1, and hence treat sarcopenia. They applied the information already available in the literature and their own hypothesis to this animal-model study.

Rapamycin works by preserving muscle size and function, along with the neuromuscular junction (NMJ) integrity. As one ages, NMJ deteriorates and this age-related NMJ instability is the driving force for mTORC1 related sarcopenia.

Rapamycin works on suppression of mTORC1 and it can reverse the damage done to NMJ along with sarcopenia associated damage to skeletal muscle. Ruegg concluded that rapamycin is extremely beneficial for the treatment of sarcopenia as it showed great results in the mice models.

Furthermore, Ruegg and his team, with the help of Zavolan and the team developed an atlas, SarcoAtlas to help the medical community further study the gene expression and aging process together.

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References

The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia

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