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Updated: Mar 7, 2026

Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

35.3K

The SETD8/PR-Set7 Methyltransferase Functions as a Barrier to Prevent Senescence-Associated Metabolic Remodeling

Hiroshi Tanaka1, Shin-Ichiro Takebayashi1, Akihisa Sakamoto1

  • 1Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.

Cell Reports
|March 2, 2017
PubMed

Insights

The SETD8 enzyme prevents cellular senescence by regulating cell metabolism. Loss of SETD8 triggers senescence, increasing ribosomal protein and p16INK4A expression, while boosting nucleolar and mitochondrial activity.

Area of Science:

  • Cellular and Molecular Biology
  • Epigenetics
  • Aging Research

Background:

  • Cellular senescence is a key process in aging and disease, characterized by irreversible growth arrest.
  • Senescent cells exhibit altered metabolism, but the regulatory mechanisms are not fully understood.
  • The histone methyltransferase SETD8 (also known as PR-Set7) plays a role in epigenetic regulation.

Purpose of the Study:

  • To investigate the role of SETD8/PR-Set7 in regulating cellular senescence.
  • To elucidate the mechanisms by which SETD8 influences nucleolar and mitochondrial function during senescence.
  • To understand the link between SETD8, chromatin modification, and metabolic remodeling in senescence.

Main Methods:

  • Investigated SETD8 protein levels in oncogene-induced and replicative senescence models.
  • Assessed the impact of SETD8 inhibition on cellular senescence.
  • Analyzed gene expression of ribosomal proteins (RPs) and p16INK4A.
  • Measured H4K20me1 levels at specific gene loci.
  • Evaluated nucleolar and mitochondrial metabolic activity.

Main Results:

  • SETD8 protein levels were decreased in senescent cells.
  • SETD8 inhibition alone induced cellular senescence.
  • Loss of SETD8 led to increased RP and p16INK4A expression with reduced H4K20me1.
  • SETD8 downregulation promoted nucleolar and mitochondrial metabolic functions.

Conclusions:

  • SETD8 acts as a crucial barrier against cellular senescence.
  • SETD8 prevents senescence by epigenetically regulating chromatin and metabolic remodeling.
  • Targeting SETD8 offers potential therapeutic strategies for age-related conditions.
Keywords:
H4K20 methylationSETD8/PR-Set7mitochondrianucleolussenescence-associated metabolic remodeling

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