Why age reduces the ability of muscles to recover
As we age, stem cells in the human body gradually lose the ability to repair damage, including those caused by natural tissue wear. Specialists of the Research Institute of the Ottawa Clinic and the University of Ottawa, working under the guidance of Professor Michael Rudnicki, have established one of the reasons for the extinction of the functionality of skeletal muscle stem cells. It consists in a progressive increase in the activity level of the JAK/STAT signaling mechanism (Janus Kinases – Signal Transducer and Activator of Transcription).
The JAK/STAT mechanism, the two key molecules of which are the JAK kinase and the STAT transcription factor, transfers signaling molecules – cytokines – from the surrounding tissue into the cell.
JAK-STAT signal path diagram (Figure from mediwiki.pp.ua )
The age-related increase in its activity changes the nature of the division of skeletal muscle stem cells, known as satellite cells. To maintain the size of their population, some of these cells must remain stem cells. The increased activity of the JAK/STAT mechanism reduces the number of symmetrical divisions with the formation of two daughter stem cells and increases the number of divisions resulting in the appearance of new muscle fibers. This reduces the population of satellite cells and reduces the ability of muscle tissue to renew and regenerate.
The authors also demonstrated that the administration of drugs that inhibit the activity of the JAK/STAT mechanism restored the ability of muscle stem cells of old mice to quickly repair damage and form new muscle tissue.
Currently, they are studying the possibilities of therapeutic use of such drugs for the treatment of diseases such as muscular dystrophy. The drugs used in the study are initially used for antitumor chemotherapy, so the authors are also looking for less toxic compounds with similar effects.
Article by Feodor D Price et al. Inhibition of JAK/STAT signaling stimulates adult satellite cell function is published in the journal Nature Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Ottawa Hospital Research Institute:
Why age reduces our stem cells' ability to repair muscle.
08.09.2014