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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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Induction and Validation of Cellular Senescence in Primary Human Cells
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ERG phase separation attenuates cellular senescence.

Lu Pu1,2, Zhiliang Zuo3,4,5, Hui Zheng6

  • 1Laboratory for Aging and Cancer Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

Iscience
|February 18, 2026
PubMed
Summary
This summary is machine-generated.

Centenarians exhibit unique chromatin accessibility linked to longevity. The transcription factor ERG regulates cellular aging via phase separation, reducing senescence and promoting resilience in extreme old age.

Keywords:
biophysical chemistrychromosome organizationmedical biochemistry

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Area of Science:

  • Genomics
  • Epigenetics
  • Cellular Biology

Background:

  • Centenarians offer insights into healthy aging mechanisms.
  • Understanding the molecular basis of longevity is crucial for developing interventions.

Purpose of the Study:

  • To identify epigenetic and molecular factors associated with exceptional longevity in centenarians.
  • To investigate the role of the transcription factor ERG in cellular aging and senescence.

Main Methods:

  • ATAC-seq and transcriptomic profiling of peripheral blood mononuclear cells from centenarians.
  • Integrative bioinformatics analysis to identify key regulators.
  • Functional studies in human cells to assess ERG's biophysical properties and effects on senescence.

Main Results:

  • A distinct chromatin accessibility landscape was identified in centenarians.
  • The transcription factor ERG was highlighted as a longevity-associated regulator.
  • ERG forms nuclear condensates via liquid-liquid phase separation, reducing senescence-related gene expression (e.g., CDKN2A) and attenuating cellular senescence phenotypes.

Conclusions:

  • Epigenomic features in centenarians are linked to transcription factor biophysical properties.
  • Liquid-phase separation of ERG is a novel regulatory mechanism in cellular aging control.
  • Phase separation may contribute to cellular resilience and longevity.