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Cell Signaling

ISSN: 2837-8253

Commentary Open Access
Volume 3 | Issue 1 | DOI: https://doi.org/10.46439/signaling.3.075

Targeting inflammation in progeria – insights from combined baricitinib and lonafarnib treatment in a mouse model of progeria

Moritz Schroll1, Karima Djabali1,*
  • 1Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine and Health, Munich Institute of Biomedical Engineering, Technical University of Munich, 85748 Garching, Germany
+ Affiliations - Affiliations

Corresponding Author

Karima Djabali, djabali@tum.de

Received Date: July 10, 2025

Accepted Date: September 08, 2025

Citation:

Schroll M, Djabali K. Targeting inflammation in progeria – insights from combined baricitinib and lonafarnib treatment in a mouse model of progeria. Cell Signal. 2025;3(1):141-146.


Copyright: © 2025 Schroll M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare and fatal premature aging disorder caused by progerin accumulation, leading to nuclear abnormalities, systemic inflammation, and early cardiovascular decline. Lonafarnib, a farnesyltransferase inhibitor (FTI), improves nuclear shape and extends lifespan, but its efficacy is limited and accompanied by pro-inflammatory effects. Here, we discuss preclinical findings from a combination therapy using the JAK1/2 inhibitor baricitinib (BAR) with FTI in a progeria mouse model. This approach produced synergistic improvements in lifespan and physical condition. Importantly, BAR counteracted the pro-inflammatory STAT1 hyperactivation induced by FTI. Combination treatment also reduced levels of senescence-associated secretory phenotype (SASP), a hallmark of senescent cells characterized by the secretion of inflammatory cytokines. Histological analysis revealed improved aortic wall thickness and reduced fibrotic remodeling (excessive buildup of connective tissue), suggesting better vascular integrity. Despite these benefits, growth impairment, lipodystrophy, and metabolic disturbances persisted, underscoring the need for further therapeutic refinements.

Keywords

HGPS, Baricitinib, Lonafarnib, Inflammation

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