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Induction and Validation of Cellular Senescence in Primary Human Cells
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Endothelial cell senescence in aging-related vascular dysfunction.

Guanghong Jia1, Annayya R Aroor1, Cassie Jia1

  • 1Diabetes and Cardiovascular Research Center, University of Missouri School of Medicine, Columbia, MO 65212, USA; Research Service, Harry S Truman Memorial Veterans Hospital, 800 Hospital Dr, Columbia, MO 65201, USA.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|May 22, 2019
PubMed
Summary

Aging vascular dysfunction is linked to endothelial cell (EC) senescence. This review updates molecular mechanisms and functional changes in EC senescence and age-associated cardiovascular disease.

Keywords:
AgingEndothelial cellHypertensionVascular stiffness

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Area of Science:

  • Cardiovascular Biology
  • Aging Research
  • Cellular Senescence

Background:

  • Cardiovascular disease risk increases with age, partly due to vascular endothelial cell (EC) senescence.
  • EC senescence involves structural and functional changes, leading to vascular dysfunction.
  • Key changes include dysregulated vascular tone, increased permeability, arterial stiffness, and impaired repair.

Purpose of the Study:

  • To provide a contemporary update on the molecular mechanisms of EC senescence in aging.
  • To review pathophysiological events and functional changes associated with EC senescence and vascular disease.
  • To elucidate the complex interplay between EC senescence and age-related cardiovascular impairment.

Main Methods:

  • Literature review focusing on molecular mechanisms of EC senescence.
  • Analysis of pathways implicated in EC senescence and vascular disease.
  • Synthesis of current understanding of functional changes in aging vasculature.

Main Results:

  • EC senescence is driven by dysregulated cell cycle, oxidative stress, altered calcium signaling, hyperuricemia, and inflammation.
  • Abnormal molecular pathways like Sirtuin 1, Klotho, FGF21, and RAAS activation are involved.
  • These changes contribute to reduced EC mitochondrial biogenesis and impaired vascular function.

Conclusions:

  • EC senescence is a critical factor in age-associated vascular dysfunction and cardiovascular disease.
  • Understanding the molecular underpinnings of EC senescence is crucial for developing interventions.
  • Further research is needed to fully elucidate the mechanisms driving EC senescence and vascular aging.