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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.
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After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
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Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
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Liver Regeneration: Polyploidy and Cellular Senescence as Potential Regulators.

Saeedeh Zare Jalise1,2,3, Sina Habibi4, Zahra Khosrowpour5

  • 1Student Research Committee, Qom University of Medical Sciences, Qom, Iran.

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|October 31, 2025
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Summary

Liver regeneration relies on hepatocyte polyploidy and cellular senescence. These processes enhance liver repair and homeostasis, offering therapeutic potential for chronic liver diseases and hepatocellular carcinoma (HCC).

Keywords:
Cellular polyploidyCellular senescenceLiver regenerationNuclear polyploidyRegulatory

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Area of Science:

  • Hepatology and Regenerative Medicine
  • Cellular Biology and Molecular Mechanisms

Background:

  • The liver's resilience and regenerative capacity are vital for its metabolic, detoxification, and immune functions.
  • Hepatocyte polyploidy (multiple chromosome sets) and cellular senescence (irreversible cell cycle arrest) are key drivers of liver regeneration and homeostasis.

Purpose of the Study:

  • To review the complex roles of hepatocyte polyploidy and cellular senescence in liver homeostasis and regeneration.
  • To explore the molecular pathways regulating these processes and their therapeutic potential.

Main Methods:

  • Review of existing literature on hepatocyte polyploidy and cellular senescence in liver biology.
  • Analysis of molecular pathways (Hippo, PI3K/Akt, p53) involved in regulating these cellular processes.

Main Results:

  • Polyploid hepatocytes contribute to liver resilience and recovery through compensatory regeneration and stem cell fusion.
  • Cellular senescence acts as a protective mechanism and promotes tissue repair via the senescence-associated secretory phenotype (SASP).
  • The interplay between polyploidy and senescence is crucial for balancing cell proliferation, differentiation, and apoptosis.

Conclusions:

  • Targeting polyploidy and senescence holds therapeutic promise for enhancing liver regeneration, preventing fibrosis, and reducing hepatocellular carcinoma (HCC) risk.
  • Further research is needed to clarify functional distinctions between diploid and polyploid hepatocytes and manage senescence's dual roles.
  • Optimizing liver health and regenerative outcomes requires deeper molecular insights and targeted interventions.