Enhanced Paracrine Action of FGF21 in Stromal Cells Delays Thymic Aging

Overview

Journal Nat Aging

Specialty Geriatrics

Date 2025 Feb 19

PMID 39972172

Authors

Yun-Hee Youm

Christy Gliniak

Yuan Zhang

Tamara Dlugos

Philipp E Scherer

Vishwa Deep Dixit

Affiliations

Soon will be listed here.

Abstract

Age-related thymic involution precedes aging of all other organs in vertebrates and initiates the process of declining T cell diversity, which leads to eventual immune dysfunction. Whether FGF21, a liver-derived pro-longevity hormone that is also produced in thymic stroma, including by adipocytes, controls the mechanism of thymic demise is incompletely understood. Here, we demonstrate that elevation of FGF21 in thymic epithelial cells (TECs) and in adipocytes protects against thymic aging, whereas conditional hepatic overexpression did not impact thymic biology in aged mice. Notably, elevation of thymic FGF21 increased naïve CD8 T cells in aged animals and extended healthspan. Mechanistically, thymic FGF21 overexpression elevated TECs and reduced fibroadipogenic cells. Ablation of β-klotho, the obligatory co-receptor for FGF21 in Foxn1 TECs, accelerated thymic aging, suggesting regulation of TECs by FGF21 is partially required for thymic lymphopoiesis. These findings establish that paracrine FGF21 improves thymic function and delays immune aging.

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