Cellular senescence in liver fibrosis: Implications for age-related chronic liver diseases

ABSTRACT

Introduction

New insights indicate a causative link between cellular senescence and liver fibrosis. Senescent hepatic stellate cells (HSCs) facilitate fibrosis resolution, while senescence in hepatocytes and cholangiocytes acts as a potent mechanism driving liver fibrogenesis. In many clinical studies, telomeres and mitochondrial DNA contents, which are both aging biomarkers, were reportedly associated with a degree of liver fibrosis in patients with chronic liver diseases (CLDs); this highlights their potential as biomarkers for liver fibrogenesis. A deeper understanding of mechanisms underlying multi-step progression of senescence may yield new therapeutic strategies for age-related chronic liver pathologies.

Areas covered

This review examines the recent findings from preclinical and clinical studies on mechanisms of senescence in liver fibrogenesis and its involvement in liver fibrosis. A comprehensive literature search in electronic databases consisting of PubMed and Scopus from inception to 31 August 2021 was performed.

Expert opinion

Cellular senescence has diagnostic, prognostic, and therapeutic potential in progressive liver complications, especially liver fibrosis. Stimulating or reinforcing the immune response against senescent cells may be a promising and forthright biotherapeutic strategy. This approach will need a deeper understanding of the immune system’s ability to eliminate senescent cells and the molecular and cellular mechanisms underlying this process.

KEYWORDS:

• Cellular senescence
• telomere shortening
• mitochondrial dysfunction
• liver fibrosis
• age-related chronic liver diseases

Acknowledgments

The authors are very grateful to Dr. Thomas Mabey for proofreading and polishing the manuscript.

Additional information

Funding

This work is supported by Mahidol University (Basic Research Fund: fiscal year 2021).