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Lookup NU author(s): Dr Marzena Kurzawa-Akanbi
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/All animals age. However, aging is a heterogeneous process, and individual organisms age differently. Moreover, within the same organism, cells or organs do not age at the same speed. For instance, neurodegeneration, a hallmark of aging, generally manifests later than other peripheral aging signs. The genetic determinants of aging are not completely understood. Gain-of-function (GoF) mutations in leucine-rich repeat kinase 2 (LRRK2GoF) are major genetic risk factors for Parkinson’s disease (PD). By analyzing PD patients and LRRK2GoF mice, we show that PD represents an accelerated aging disorder driven by STING-dependent inflammation. This inflammation begins peripherally, disrupts the blood-brain barrier, and causes dopaminergic neurodegeneration. Mechanistically, aging or LRRK2GoF causes endolysosomal decline, resulting in cytosolic self-DNA accumulation and the release of DNA-containing extracellular vesicles (EVs) that activate the cGAS-STING pathway within and between cells. Our findings identify LRRK2GoF as a key driver of accelerated aging and systemic inflammaging through DNA-containing EVs, highlighting potential therapeutic targets to counteract inflammaging and neurodegeneration.
Author(s): Oberg M, Myers C, Saffarzadeh N, Maric I, Murillo-Leon M, Stromberg A, Fabrikova D, Fabrik I, Rivas-Galvez L, Deshmukh MV, Enriquez J, Ali KX, Crescitelli R, Angeletti D, Sayin VI, Jin T, Rafie K, Skibicka KP, Kurzawa-Akanbi M, Paul G, Gekara NO, Hartlova A
Publication type: Article
Publication status: Published
Journal: Cell Reports
Year: 2026
Volume: 45
Issue: 7
Print publication date: 28/07/2026
Online publication date: 03/07/2026
Acceptance date: 15/06/2026
Date deposited: 14/07/2026
ISSN (print): 2639-1856
ISSN (electronic): 2211-1247
Publisher: Elsevier
URL: https://doi.org/10.1016/j.celrep.2026.117640
DOI: 10.1016/j.celrep.2026.117640
Data Access Statement: Raw data for RNA-seq have been deposited at NCBI Sequence Read Archive under BioProject PRJNA1119718. This paper does not report original code. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request
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