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Updated: Feb 12, 2026
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Generation of a Humanized Mouse Liver Using Human Hepatic Stem Cells
Published on: August 29, 2016
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Targeted Hepatic Methylation-Controlled J Protein Inhibition Mitigates Postsurgical Liver Injury and
Kenneth Meza Monge1, Akshay Pratap1, Kevin M Najarro1
1Division of GI, Trauma and Endocrine Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Shock (Augusta, Ga.)
|February 11, 2026
Summary
Targeted inhibition of Methylation-Controlled J protein (MCJ) in the liver prevents age-related surgical complications. Silencing MCJ in aged mice improved liver function, reduced neuroinflammation, and preserved cognitive function post-surgery.
Area of Science:
- Gerontology
- Hepatology
- Neuroscience
Background:
- Advanced age increases surgical complication risk, including neurological dysfunction.
- Age-related liver function changes are critical but understudied in perioperative risk.
- Methylation-Controlled J protein (MCJ) exacerbates aging-related oxidative stress and metabolic decline.
Purpose of the Study:
- To investigate the role of hepatic MCJ in age-related perioperative neurological complications.
- To assess the therapeutic potential of MCJ inhibition in mitigating these effects.
Main Methods:
- Aged and young mice underwent surgery or sham procedures.
- Hepatocyte-targeted GalNAc-siMCJ was administered pre-surgery to inhibit MCJ.
- Assessed liver injury, metabolic dysfunction, blood-brain barrier integrity, neuroinflammation, and cognitive function.
Main Results:
- Aged mice showed subclinical liver injury, metabolic dysfunction, blood-brain barrier disruption, neuroinflammation, and cognitive impairment post-surgery.
- Hepatic MCJ silencing prevented these age-related alterations in aged mice.
- MCJ inhibition reduced inflammatory markers in young mice.
Conclusions:
- Targeted hepatic MCJ inhibition mitigates subclinical liver injury and neuroinflammation in aged mice after surgery.
- Modulating the liver-brain axis via MCJ inhibition is a potential strategy for preventing perioperative neurological complications in older adults.
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