Fibroblast growth factor 21 (FGF21) in healthy aging and aging-related diseases

Angeliki Vakka

1,#

Frederick Sherman

2,#

Kajol Thapa

Konstantinos Tsioufis

Konstantinos Drosatos

2,*

Affiliation +

*Correspondence to: Konstantinos Drosatos, Metabolic Biology Laboratory, Cardiovascular Center, Department of Pharmacology, Physiology and Neurobiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. E-mail: k.drosatos@uc.edu

Geromedicine. 2027;3:202622. 10.70401/Geromedicine.2026.0045

Received: April 04, 2026Accepted: October 22, 2026Published: October 26, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

The global human population is aging rapidly, and the prevalence of aging-related diseases is increasing. Thus, understanding the molecular pathways involved in the hallmarks of aging is essential for the development of therapies that promote healthy aging and extend lifespan. Fibroblast growth factor (FGF) 21 has emerged as a promising therapeutic candidate due to its pleiotropic beneficial roles in metabolism, stress response, and tissue repair through pathways that regulate oxidative stress and cellular senescence. Preclinical studies have associated FGF21 with beneficial effects against metabolic syndrome, liver steatosis, kidney injury, and neurodegenerative disorders that occur in aged individuals. Conversely, FGF21 has also been linked to skeletal muscle loss and concentric cardiac hypertrophy. This review summarizes current evidence on FGF21 signaling and its effects on either healthy aging or aging-related diseases, highlighting its tissue-, time-, origin- and stress- dependent effects.

Keywords

Aging, FGF21, organ dysfunction, metabolism, interorgan communication

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Vakka A, Sherman F, Thapa K, Tsioufis K, Drosatos K. Fibroblast growth factor 21 (FGF21) in healthy aging and aging-related diseases. Geromedicine. 2027;3:202622. https://doi.org/10.70401/Geromedicine.2026.0045

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Geromedicine

Fibroblast growth factor 21 (FGF21) in healthy aging and aging-related diseases

Angeliki Vakka

Frederick Sherman

Kajol Thapa

Konstantinos Tsioufis

Konstantinos Drosatos

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Fibroblast growth factor 21 (FGF21) in healthy aging and aging-related diseases

Angeliki Vakka

Frederick Sherman

Kajol Thapa

Konstantinos Tsioufis

Konstantinos Drosatos

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