FGF21 Hormone Offers Hope for Strengthening Immune Function in Older Adults

The University of Texas Health Science Center at San Antonio (UT Health San Antonio) scientists have uncovered a crucial pathway that may help preserve thymic function as we age. The findings, published in Nature Aging in February, focus on fibroblast growth factor FGF21, a peptide hormone that regulates T-cells and may help preserve thymic size over time.

A small gland located in the upper chest under the breastbone, the thymus plays a vital role in the immune system by training the body’s T-cells to fight infections. The thymus shrinks with age, contributing to a weaker immune system in adulthood. In experiments with mouse models, increasing FGF21 preserved both the size and function of the thymus, allowing for a broader range of T-cells to develop.

“This research could be pivotal in developing a way to preserve strong immune responses across a lifetime,” said Ann Griffith, PhD, assistant professor in the Department of Microbiology, Immunology and Molecular Genetics at UT Health San Antonio. “This is an exciting step forward in finding targets that can durably restore thymic function in older people and improve their immune response.”

This study, led by Griffith, followed up on earlier transcriptomic work that investigated how genes changed during thymic regeneration. The previous study, and work from other labs, found that FGF21 was closely tied to thymic growth.

“We saw FGF21 impacted the morphology of these labyrinth-shaped cells, and that was associated with overall tissue size,” said Griffith. “FGF21 can signal directly to the stromal cells inside the thymus and may also be signaling to other cells in a way that impacts the morphology.”

As people age, the body’s ability to regenerate the thymus and support young T-cells slows down. This leaves older people more vulnerable to infections and tumor recurrence. An increase in FGF21 shows promise for slowing thymic atrophy, but it does not completely prevent it.

The study also highlighted FGF21’s potential in reducing inflammation and autoimmunity, conditions that increase as thymic function declines with age.

“Part of the T-cells’ education in this ‘school’ is to make sure that if they are recognizing our own tissues, we remove these cells. We’ve seen this function diminish with age, and this protein was able to mitigate that to potentially allow for better tolerance in T-cells that come out of the thymus,” added Griffith.

Reference: Wedemeyer SA, Jones NE, Raza IGA, et al. Paracrine FGF21 dynamically modulates mTOR signaling to regulate thymus function across the lifespan. Nat Aging. 2025;5(4):588-606. doi: 10.1038/s43587-024-00801-1

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