Restoring Youthful Muscle Regeneration

The regenerative ability of muscle declines as we get older, and new research has indicated that declining levels of two proteins called β1-integrin and fibonectin are partly to blame

Healthy, young muscle is supplied by a similarly youthful store of stem cells (also known as satellite cells) found at the periphery of muscle fibres. These remain largely dormant until damage occurs; springing into action and creating a fresh, new set of fibres. Keeping an effective, dormant store of stem cells is essential for maintaining this regenerative ability throughout life, but elderly muscles host a diminished population of stem cells. 

"Inefficient muscular healing in the elderly is a significant clinical problem and therapeutic approaches are much needed, especially given the aging population–and I am including myself in this population. Finding a way to target muscle stem cells could greatly improve muscle renewal in older individuals"  

What goes wrong as we age?

A new study published in Nature Medicine is now suggesting that levels of a protein called β1-integrin are crucial for regulating this stem cells cycle and facilitating muscle rejuvenation. Integrins are critical proteins that play an important role in cellular communication and interaction with the local environment - particularly influencing division and growth.

Researchers involved in the study discovered that levels of β1-integrin decline in old muscle stem cells, but more importantly that restoring levels of this protein restored lost regenerative abilities. Increasing levels of β1-integrin in a mouse model of muscular dystrophy increased muscle regeneration, strength and function. 

A normal muscle (left) compard to a muscle without β1-integrin. Credit: Chen-Ming Fan and Michelle Rozo

It's not all about β1-integrin

In a collaborative research effort with other institutions, the team of scientists attempted to understand what was going on in greater detail. β1-integrin interacts with many other proteins, and the researchers identified another important connection with a protein called fibronectin. Levels of fibronectin similarly fall with age in muscles, and once again restoring it appeared to repair stem cell function. The relationshup between fibronectin and muscle stem cell aging was discussed in a 2nd paper.

"Taken together, our results show that aged muscle stem cells with compromised b1-integrin activity and aged muscles with insufficient amount of fibronectin both root causes of muscle aging. This makes b1-integrin and fibronectin very promising therapeutic targets"

Read more at MedicalXpress