Vascular ageing and endothelial cell senescence: Molecular mechanisms of physiology and diseases

Mech Ageing Dev. 2016 Oct:159:14-21. doi: 10.1016/j.mad.2016.05.003. Epub 2016 May 4.

Abstract

Ageing leads to a progressive deterioration of structure and function of all organs over the time. During this process endothelial cells undergo senescence and manifest significant changes in their properties, resulting in impairment of the vascular functionality and neo-angiogenic capability. This ageing-dependent impairment of endothelial functions is considered a key factor contributing to vascular dysfunctions, which is responsible of several age-related diseases of the vascular system and other organs. Several mechanisms have been described to control ageing-related endothelial cell senescence including microRNAs, mitochondrial dysfunction and micro environmental stressors, such as hypoxia. In this review, we attempt to summarize the recent literature in the field, discussing the major mechanisms involved in endothelial cell senescence. We also underline key molecular aspects of ageing-associated vascular dysfunction in the attempt to highlight potential innovative therapeutic targets to delay the onset of age-related diseases.

Keywords: Endotheliocyte; Endothelium; Hypoxia; Mitochondrial dysfunction; Oxidative stress; Transglutaminase 2; VEGF; microRNAs; p53 family; p73.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging* / metabolism
  • Aging* / pathology
  • Animals
  • Cellular Senescence*
  • Endothelial Cells* / metabolism
  • Endothelial Cells* / pathology
  • Humans
  • Hypoxia* / metabolism
  • Hypoxia* / pathology
  • Hypoxia* / therapy
  • MicroRNAs / metabolism
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Vascular Diseases* / metabolism
  • Vascular Diseases* / pathology
  • Vascular Diseases* / therapy

Substances

  • MicroRNAs