PMID- 37310873
OWN - NLM
STAT- MEDLINE
DCOM- 20231011
LR  - 20240210
IS  - 1758-535X (Electronic)
IS  - 1079-5006 (Print)
IS  - 1079-5006 (Linking)
VI  - 78
IP  - 10
DP  - 2023 Oct 9
TI  - Interleukin-6 Drives Mitochondrial Dysregulation and Accelerates Physical 
      Decline: Insights From an Inducible Humanized IL-6 Knock-In Mouse Model.
PG  - 1740-1752
LID - 10.1093/gerona/glad147 [doi]
AB  - 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.
CI  - (c) 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.
FAU - Nidadavolu, Lolita S
AU  - Nidadavolu LS
AUID- ORCID: 0000-0003-2433-0728
AD  - Division of Geriatrics and Gerontology, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland, USA.
FAU - Cosarderelioglu, Caglar
AU  - Cosarderelioglu C
AUID- ORCID: 0000-0002-7560-1287
AD  - Division of Geriatrics and Gerontology, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland, USA.
FAU - Merino Gomez, Alessandra
AU  - Merino Gomez A
AD  - Division of Geriatrics and Gerontology, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland, USA.
FAU - Wu, Yuqiong
AU  - Wu Y
AD  - Division of Geriatrics and Gerontology, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland, USA.
FAU - Bopp, Taylor
AU  - Bopp T
AD  - Department of Physical Medicine and Rehabilitation, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, USA.
FAU - Zhang, Cissy
AU  - Zhang C
AD  - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Nguyen, Tu
AU  - Nguyen T
AD  - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Marx-Rattner, Ruth
AU  - Marx-Rattner R
AD  - Division of Geriatrics and Gerontology, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland, USA.
FAU - Yang, Huanle
AU  - Yang H
AD  - Division of Geriatrics and Gerontology, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland, USA.
FAU - Antonescu, Corina
AU  - Antonescu C
AD  - Department of Genetic Medicine, John Hopkins University School of Medicine, 
      Baltimore, Maryland, USA.
FAU - Florea, Liliana
AU  - Florea L
AUID- ORCID: 0000-0001-8124-2324
AD  - Department of Genetic Medicine, John Hopkins University School of Medicine, 
      Baltimore, Maryland, USA.
FAU - Talbot, Conover C
AU  - Talbot CC
AD  - Institute for Basic Biomedical Sciences, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland, USA.
FAU - Smith, Barbara
AU  - Smith B
AD  - Department of Cell Biology, Imaging Facility, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland, USA.
FAU - Foster, D Brian
AU  - Foster DB
AD  - Division of Cardiology, Department of Medicine, Johns Hopkins University, 
      Baltimore, Maryland, USA.
FAU - Fairman, Jennifer E
AU  - Fairman JE
AD  - Division of Cellular and Molecular Medicine, Department of Art as Applied to 
      Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
FAU - Yenokyan, Gayane
AU  - Yenokyan G
AUID- ORCID: 0000-0003-1482-5612
AD  - Johns Hopkins Biostatistics Center, Johns Hopkins Bloomberg School of Public 
      Health, Baltimore, Maryland, USA.
FAU - Chung, Tae
AU  - Chung T
AD  - Department of Physical Medicine and Rehabilitation, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, USA.
AD  - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Le, Anne
AU  - Le A
AD  - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Walston, Jeremy D
AU  - Walston JD
AD  - Division of Geriatrics and Gerontology, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland, USA.
FAU - Abadir, Peter M
AU  - Abadir PM
AD  - Division of Geriatrics and Gerontology, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland, USA.
LA  - eng
GR  - P30 AG021334/AG/NIA NIH HHS/United States
GR  - R01 AG046441/AG/NIA NIH HHS/United States
GR  - R01AG046441/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Gerontol A Biol Sci Med Sci
JT  - The journals of gerontology. Series A, Biological sciences and medical sciences
JID - 9502837
RN  - 0 (Interleukin-6)
SB  - IM
MH  - Mice
MH  - Humans
MH  - Animals
MH  - *Interleukin-6/genetics/metabolism
MH  - *Frailty
MH  - Mitochondria/genetics/metabolism
MH  - Disease Models, Animal
MH  - Muscle, Skeletal/metabolism
PMC - PMC10562892
OTO - NOTNLM
OT  - Inflammation
OT  - Mitochondria dysregulation
OT  - Physical decline
COIS- None.
EDAT- 2023/06/13 19:15
MHDA- 2023/10/11 06:45
PMCR- 2024/06/13
CRDT- 2023/06/13 13:02
PHST- 2023/02/27 00:00 [received]
PHST- 2024/06/13 00:00 [pmc-release]
PHST- 2023/10/11 06:45 [medline]
PHST- 2023/06/13 19:15 [pubmed]
PHST- 2023/06/13 13:02 [entrez]
AID - 7197123 [pii]
AID - glad147 [pii]
AID - 10.1093/gerona/glad147 [doi]
PST - ppublish
SO  - J Gerontol A Biol Sci Med Sci. 2023 Oct 9;78(10):1740-1752. doi: 
      10.1093/gerona/glad147.