Targeted Deletion of Interleukin-6 in a Mouse Model of Chronic Inflammation Demonstrates Opposing Roles in Aging: Benefit and Harm.
Interleukin-10
Interleukin-6
Knockout
Lysophosphatidylcholine
Mitochondria
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:
18 01 2021
18 01 2021
Historique:
received:
05
06
2020
pubmed:
26
6
2020
medline:
15
7
2021
entrez:
26
6
2020
Statut:
ppublish
Résumé
Chronic inflammation (CI) in older adults is associated with reduced health span and life span. Interleukin-6 (IL-6) is one CI marker that is strongly associated with adverse health outcomes and mortality in aging. We have previously characterized a mouse model of frailty and chronic inflammatory pathway activation (IL-10tm/tm, IL-10 KO) that demonstrates the upregulation of numerous proinflammatory cytokines, including IL-6. We sought to identify a more specific role for IL-6 within the context of CI and aging and developed a mouse with targeted deletion of both IL-10 and IL-6 (IL-10tm/tm/IL-6tm/tm, DKO). Phenotypic characteristics, cytokine measurements, cardiac myocardial oxygen consumption, physical function, and survival were measured in DKO mice and compared to age- and gender-matched IL-10 KO and wild-type mice. Our findings demonstrate that selective knockdown of IL-6 in a frail mouse with CI resulted in the reversal of some of the CI-associated changes. We observed increased protective mitochondrial-associated lipid metabolites, decreased cardiac oxaloacetic acid, improved myocardial oxidative metabolism, and better short-term functional performance in DKO mice. However, the DKO mice also demonstrated higher mortality. This work shows the pleiotropic effects of IL-6 on aging and frailty.
Identifiants
pubmed: 32585682
pii: 5862779
doi: 10.1093/gerona/glaa156
pmc: PMC7812426
doi:
Substances chimiques
IL10 protein, mouse
0
Interleukin-6
0
Lipids
0
interleukin-6, mouse
0
Interleukin-10
130068-27-8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
211-215Subventions
Organisme : NIA NIH HHS
ID : P30 AG021334
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG046441
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG058527
Pays : United States
Organisme : NIH HHS
ID : S10 OD025226
Pays : United States
Informations de copyright
© The Author(s) 2020. 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.
Références
J Gerontol A Biol Sci Med Sci. 2020 Jan 20;75(2):207-217
pubmed: 30272137
J Gerontol A Biol Sci Med Sci. 2019 Feb 15;74(3):343-349
pubmed: 29534173
Circ Cardiovasc Imaging. 2010 Mar;3(2):211-22
pubmed: 20233863
Biochem Biophys Res Commun. 2003 Oct 17;310(2):550-4
pubmed: 14521945
J Gerontol A Biol Sci Med Sci. 2008 Apr;63(4):391-8
pubmed: 18426963
Aging Cell. 2019 Apr;18(2):e12915
pubmed: 30719830
J Nucl Med. 2001 Aug;42(8):1174-82
pubmed: 11483676
Cell Rep. 2019 Apr 9;27(2):491-501.e6
pubmed: 30970252
Atherosclerosis. 2010 Jan;208(1):10-8
pubmed: 19570538
J Am Geriatr Soc. 1999 Jun;47(6):639-46
pubmed: 10366160
FEBS Lett. 2005 Apr 11;579(10):2035-9
pubmed: 15811314
J Gerontol A Biol Sci Med Sci. 2019 Jan 1;74(1):62-67
pubmed: 29788121
J Immunol. 2012 Oct 1;189(7):3669-80
pubmed: 22933625
Age (Dordr). 2014 Feb;36(1):21-30
pubmed: 23695949
Age (Dordr). 2012 Jun;34(3):705-15
pubmed: 21633802
PLoS One. 2017 Dec 21;12(12):e0186811
pubmed: 29267271
Free Radic Res. 2012 Sep;46(9):1108-14
pubmed: 22640231
Ageing Res Rev. 2016 Nov;31:1-8
pubmed: 27592340
J Gerontol A Biol Sci Med Sci. 2014 Feb;69(2):165-73
pubmed: 23689826
Front Physiol. 2015 Feb 18;6:48
pubmed: 25741287