Help us: Donate
Follow us on:



Promoting Muscle Regeneration With an Immune Factor

This vital factor declines with aging.

Muscle factorMuscle factor

A paper published today in Nature Aging has shown that a macrophage-regulating factor has a significant impact on muscle regeneration.

Healing slows with aging

The researchers note two key reasons for the decline of regenerative abilities with aging. The first is stem cell exhaustion, the gradual depletion of stem cells and ensuing lack of functional cells. The second, which this paper focuses on, is changes to the surrounding environment, the effects of which are the subject of well-known parabiosis experiments.

However, instead of experimenting with young blood as a whole, the researchers focus on just one of its factors: mesencephalic astrocyte-derived neurotrophic factor (MANF) [1], which declines with aging and has been shown to have positive effects on the retina [2] and other tissues [3].

A factor necessary for regeneration

The researchers created a population of mice that stopped producing MANF upon exposure to a hormone therapy. When the quadriceps of these mice were injured and MANF blocked, these mice were found to have substantially weaker regeneration, with fewer new muscle fibers, fewer muscle stem cells, and many more dead fibers remaining in the tissue.

This is explained by the cellular populations in the tissue. Mice without MANF2 were found to have roughly the same amounts of pro-inflammatory macrophages but far fewer macrophages associated with regeneration. By blocking MANF at different times, the researchers showed that this particular effect occurs while the animal is injured; temporarily blocking MANF before an injury did not have an effect.

Further experiments in cellular culture, using cells from wholly MANF-deficient mice, showed that MANF is essential to macrophages changing their phenotypes towards regeneration and away from inflammation. MANF was also found to be valuable for lysosomal degradation of foreign proteins, and macrophages without it were unable to properly respond to necrotic debris, which is a logical explanation for the dead fibers remaining in MANF-deficient mice.

Restoring age-related MANF decline

This study confirmed that old (22-24 months) mice have substantially fewer healing-oriented macrophages than young (2-6 months) mice. Gene expression analysis showed that their macrophages had some things in common with young, MANF-deficient macrophages, particularly the problems with lysosomal degradation, but the aged cells also had other problems with cellular movement structures.

The researchers performed their final and most crucial experiment, delivering recombinant MANF to aged mice. This treatment worked; macrophages were restored to youthful populations, necrotic fibers were more thoroughly cleared, and new muscle fibers were created in greater quantities.

MANF therapy at 4 μg i.m. resulted in a complete rescue of the repair-associated myeloid response.


While this is a mouse study, MANF appears to play the same basic biological role in human beings. Further work, development, and clinical trials will be necessary to determine if MANF-based treatments can restore health and function to old, damaged muscle tissue.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. We are committed to responsible journalism, free from commercial or political influence, that allows you to make informed decisions about your future health.

All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future. You can support us by making a donation or in other ways at no cost to you.

Vitalik Buterin Exclusive Interview: Longevity, AI and More

Vitalik Buterin holding Zuzu, the puppy rescued by people of Zuzalu. Photo: Michelle Iai Don’t try finding Zuzalu on a...

Centenarians Have Slightly Different Gut Ecologies

Researchers publishing in Nature Microbiology have determined that the viruses populating the intestines of centenarians are slightly different from those...

Hypoxia Extends Median Lifespan in Fast-Aging Mice by 50%

Scientists have found that continuous oxygen restriction drastically extends the lifespan of progeroid mice, but the effect's mechanism remains a...

Discovering Why Adrenal Cancer Is More Dangerous for Women

A paper published today in Nature Aging has explained a relationship between cellular senescence, cancer of the adrenal glands, and...


[1] Sousa-Victor, P., Neves, J., Cedron-Craft, W., Ventura, P. B., Liao, C. Y., Riley, R. R., … & Jasper, H. (2019). MANF regulates metabolic and immune homeostasis in ageing and protects against liver damage. Nature metabolism, 1(2), 276-290.

[2] Neves, J., Zhu, J., Sousa-Victor, P., Konjikusic, M., Riley, R., Chew, S., … & Lamba, D. A. (2016). Immune modulation by MANF promotes tissue repair and regenerative success in the retina. Science, 353(6294), aaf3646.

[3] JOntti, M., & Harvey, B. K. (2020). Trophic activities of endoplasmic reticulum proteins CDNF and MANF. Cell and Tissue Research, 382(1), 83-101.

About the author
Josh Conway

Josh Conway

Josh is a professional editor and is responsible for editing our articles before they become available to the public as well as moderating our Discord server. He is also a programmer, long-time supporter of anti-aging medicine, and avid player of the strange game called β€œreal life.” Living in the center of the northern prairie, Josh enjoys long bike rides before the blizzards hit.
No Comments
Write a comment:


Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.