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Related Concept Videos

Liver Regeneration01:24

Liver Regeneration

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The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
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Related Experiment Video

Updated: Jul 16, 2025

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
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Data-driven transcriptomics analysis identifies PCSK9 as a novel key regulator in liver aging.

Muhammad Arif1,2, Csaba Matyas1, Partha Mukhopadhyay1

  • 1Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute On Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.

Geroscience
|September 19, 2023
PubMed
Summary

Aging significantly alters liver function, causing mitochondrial dysfunction, stress, and inflammation. Our study identified PCSK9 as a key gene in liver aging, offering a potential therapeutic target for improving liver health in older adults.

Keywords:
AgingLiverMetabolismNetwork biologyPCSK9Rat modelSystems biologyTranscriptomics

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Area of Science:

  • Gerontology and Hepatology
  • Molecular Biology
  • Systems Biology

Background:

  • The aging process induces significant pathological changes in the liver, impacting overall health.
  • Understanding these age-related liver alterations is crucial for developing targeted interventions.

Purpose of the Study:

  • To systematically investigate the effects of aging on liver function using a multi-omics approach.
  • To identify key genes and pathways involved in liver aging.
  • To validate findings in both rat models and human aging studies.

Main Methods:

  • Utilized a National Institute of Aging rat aging model (Fischer 344 rats, young vs. aging).
  • Employed systems biology approaches, including genome-wide transcriptomics, biochemical assays, histology, and immunohistochemistry.
  • Performed co-expression network analysis and validated findings with human aging datasets and single-cell RNA-sequencing.

Main Results:

  • Identified widespread pathological changes in aging livers: mitochondrial dysfunction, oxidative stress, decreased NAD+ levels, impaired synthesis, inflammation, lipid metabolism disruption, apoptosis, senescence, and fibrosis.
  • Discovered novel driver genes for liver aging through co-expression network analysis.
  • Validated proprotein convertase subtilisin/kexin type 9 (PCSK9) as a liver-specific gene implicated in aging.

Conclusions:

  • Aging profoundly impacts liver biology through multiple interconnected pathways.
  • PCSK9 is identified as a potential therapeutic target for mitigating age-related liver pathology.
  • This research opens avenues for interventions to enhance liver health during aging.