Vascular aging: chronic oxidative stress and impairment of redox signaling-consequences for vascular homeostasis and disease

Ann Med. 2013 Feb;45(1):17-36. doi: 10.3109/07853890.2011.645498. Epub 2012 Mar 1.


Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the 'free radical theory of aging' but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging / metabolism*
  • Blood Vessels / metabolism*
  • Blood Vessels / physiopathology
  • Endothelium / metabolism
  • Free Radicals / metabolism
  • Homeostasis / physiology
  • Humans
  • Mitochondria
  • Nitric Oxide / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress*
  • Prostaglandins / metabolism
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction


  • Free Radicals
  • Prostaglandins
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Nitric Oxide