MANF Upregulation in Macrophages Improves Muscle Regeneration in Old Mice

Regeneration following injury is an intricate, coordinated dance between stem cells, various types of somatic cell, and immune cells. Age-related changes in any of those cell populations may contribute to the declining ability to heal injuries observed in later life. Researchers here identify a specific change in the innate immune cells called macrophages that produces a significant impairment in wound healing in mice. This may prove to the basis for therapies to improve regeneration in older people, time will tell.

As our organism ages, the muscles lose the capacity to regenerate. Researchers have found a protein that regulates the function of a subset of immune cells, macrophages, by promoting their ability to clear residues in the regenerating muscle. The behavior of macrophages is altered in aged mice. Macrophages are a type of immune cells that are capable of phagocytosis, the process of ingestion and elimination of particles inside cells. During regeneration the macrophages are responsible for clearing the dead cells from the muscle after injury, which is a normal step of the process of muscle regeneration.

The researchers found that macrophages in aged mice have reduced levels of a protein, called MANF, that is crucial for this process. "In fact, this protein is so important in this process that if we decrease MANF levels in the macrophages in younger mice, their ability to regenerate muscle is also impaired. On the other hand, increasing the levels of the protein MANF in aged muscle is sufficient to recover muscle's regenerative capacity."

"A central promise of regenerative medicine is the ability to repair aged or diseased organs using stem cells. This approach will likely become an effective strategy for organ rejuvenation, holding the potential to increase human health span by delaying age-related diseases. Our study shows that immune aging is an important obstacle to the regenerative capacity of aged muscle."


Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.