Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging

Juan Ignacio Jiménez-Loygorri, Beatriz Villarejo-Zori, Álvaro Viedma-Poyatos, Juan Zapata-Muñoz, Rocío Benítez-Fernández, María Dolores Frutos-Lisón, Francisco A. Tomás-Barberán, Juan Carlos Espín, Estela Area-Gómez, Aurora Gomez-Duran and Patricia Boya ()
Additional contact information
Juan Ignacio Jiménez-Loygorri: Centro de Investigaciones Biológicas Margarita Salas, CSIC
Beatriz Villarejo-Zori: Centro de Investigaciones Biológicas Margarita Salas, CSIC
Álvaro Viedma-Poyatos: Centro de Investigaciones Biológicas Margarita Salas, CSIC
Juan Zapata-Muñoz: Centro de Investigaciones Biológicas Margarita Salas, CSIC
Rocío Benítez-Fernández: Centro de Investigaciones Biológicas Margarita Salas, CSIC
María Dolores Frutos-Lisón: Food & Health Lab, Research Group on Quality, Safety, and Bioactivity of Plant Foods, CEBAS-CSIC
Francisco A. Tomás-Barberán: Food & Health Lab, Research Group on Quality, Safety, and Bioactivity of Plant Foods, CEBAS-CSIC
Juan Carlos Espín: Food & Health Lab, Research Group on Quality, Safety, and Bioactivity of Plant Foods, CEBAS-CSIC
Estela Area-Gómez: Centro de Investigaciones Biológicas Margarita Salas, CSIC
Aurora Gomez-Duran: Centro de Investigaciones Biológicas Margarita Salas, CSIC
Patricia Boya: Centro de Investigaciones Biológicas Margarita Salas, CSIC

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Macroautophagy decreases with age, and this change is considered a hallmark of the aging process. It remains unknown whether mitophagy, the essential selective autophagic degradation of mitochondria, also decreases with age. In our analysis of mitophagy in multiple organs in the mito-QC reporter mouse, mitophagy is either increased or unchanged in old versus young mice. Transcriptomic analysis shows marked upregulation of the type I interferon response in the retina of old mice, which correlates with increased levels of cytosolic mtDNA and activation of the cGAS/STING pathway. Crucially, these same alterations are replicated in primary human fibroblasts from elderly donors. In old mice, pharmacological induction of mitophagy with urolithin A attenuates cGAS/STING activation and ameliorates deterioration of neurological function. These findings point to mitophagy induction as a strategy to decrease age-associated inflammation and increase healthspan.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45044-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45044-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45044-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().