FGF21 Muscle Hormone Associated with Slow ALS Progression and Extended Survival

BUFFALO, NY — September 18, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 9, 2025, titled “The myokine FGF21 associates with enhanced survival in ALS and mitigates stress-induced cytotoxicity.” In this study, led by first author Abhishek Guha and corresponding author Peter H. King from the University of Alabama at Birmingham and the Birmingham Veterans Affairs Medical Center, researchers discovered that a hormone called FGF21, which is released by muscles, is elevated in people with amyotrophic lateral sclerosis (ALS) and may play a protective role. These findings are especially relevant because ALS is a fatal and currently incurable neurodegenerative disease. Amyotrophic lateral sclerosis is an age-related and progressive condition that affects the nerve cells responsible for muscle control. While some treatments can slow the disease, there is still a need to understand why ALS progresses at different rates in different individuals. “In a prior muscle miRNA sequencing investigation, we identified altered FGF pathways in ALS muscle, leading us to investigate FGF21.” The research team analyzed muscle biopsies, spinal cord tissue, and blood samples from ALS patients and found that FGF21 levels were significantly elevated. This increase was particularly evident in atrophied muscle fibers—those that had shrunk due to nerve loss—and in the surrounding tissue. Importantly, patients with higher plasma levels of FGF21 showed slower loss of function and longer survival, with some living more than six years after diagnosis. Using animal models and cultured cells, the researchers demonstrated that FGF21 levels rise even in the early, symptom-free stages of ALS. The hormone appeared to protect both muscle and motor neurons from stress-related damage. When added to stressed cells, FGF21 improved cell survival and reduced markers of cell death. In human muscle cells, FGF21 also supported the formation of new muscle fibers, a process known as myogenesis. Blood tests revealed that patients with higher levels of FGF21 not only experienced slower disease progression but also tended to have a higher body mass index (BMI), a factor previously associated with longer survival in ALS. This suggests that FGF21 may reflect a patient’s ability to counteract ALS through natural protective mechanisms. It could also serve as a biomarker to monitor disease severity and potentially guide treatment decisions. The study also investigated how FGF21 communicates with cells. It found that the hormone’s activity depends on a protein called β-Klotho, which was also altered in ALS-affected tissues. These changes were especially noticeable in motor neurons and muscle cells under stress, further highlighting FGF21’s role in the body’s response to damage. While the study does not show that FGF21 can be used as a treatment, it highlights the hormone as a promising target for future research, clinical trials, and strategies to slow ALS progression by leveraging the body’s natural protective systems. DOI - https://doi.org/10.18632/aging.206298 Corresponding author - Peter H. King - phking@uabmc.edu Abstract video - https://www.youtube.com/watch?v=zEGMxQrxZxE Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, fibroblast growth factor, 21 β-Klotho, ALS biomarker, human skeletal muscle, motor neurons To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM