Interleukin-6 Drives Mitochondrial Dysregulation and Accelerates Physical Decline: Insights From an Inducible Humanized IL-6 Knock-In Mouse Model.
Inflammation
Mitochondria dysregulation
Physical decline
Journal
The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
Titre abrégé: J Gerontol A Biol Sci Med Sci
Pays: United States
ID NLM: 9502837
Informations de publication
Date de publication:
09 10 2023
09 10 2023
Historique:
received:
27
02
2023
pmc-release:
13
06
2024
medline:
11
10
2023
pubmed:
13
6
2023
entrez:
13
6
2023
Statut:
ppublish
Résumé
Chronic activation of inflammatory pathways (CI) and mitochondrial dysfunction are independently linked to age-related functional decline and early mortality. Interleukin 6 (IL-6) is among the most consistently elevated chronic activation of inflammatory pathways markers, but whether IL-6 plays a causative role in this mitochondrial dysfunction and physical deterioration remains unclear. To characterize the role of IL-6 in age-related mitochondrial dysregulation and physical decline, we have developed an inducible human IL-6 (hIL-6) knock-in mouse (TetO-hIL-6mitoQC) that also contains a mitochondrial-quality control reporter. Six weeks of hIL-6 induction resulted in upregulation of proinflammatory markers, cell proliferation and metabolic pathways, and dysregulated energy utilization. Decreased grip strength, increased falls off the treadmill, and increased frailty index were also observed. Further characterization of skeletal muscles postinduction revealed an increase in mitophagy, downregulation of mitochondrial biogenesis genes, and an overall decrease in total mitochondrial numbers. This study highlights the contribution of IL-6 to mitochondrial dysregulation and supports a causal role of hIL-6 in physical decline and frailty.
Identifiants
pubmed: 37310873
pii: 7197123
doi: 10.1093/gerona/glad147
pmc: PMC10562892
doi:
Substances chimiques
Interleukin-6
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1740-1752Subventions
Organisme : NIA NIH HHS
ID : P30 AG021334
Pays : United States
Organisme : NIH HHS
ID : R01AG046441
Pays : United States
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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