Enhanced paracrine action of FGF21 in stromal cells delays thymic aging.

Yun-Hee Youm, Christy Gliniak, Yuan Zhang, Tamara Dlugos, Philipp E Scherer, Vishwa Deep Dixit

Department of Pathology, Yale School of Medicine, New Haven, CT, USA.Department of Pathology, Yale School of Medicine, New Haven, CT, USA. · pubmed

Paper

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

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Research summary

Elevation of FGF21 in thymic epithelial cells and adipocytes protects against thymic aging and extends healthspan in aged mice. This research addresses the mechanisms of thymic aging, which is a root cause of immune dysfunction associated with aging, thus contributing to the understanding of longevity and potential interventions.

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