Aging and vascular endothelial function in humans.
Advancing age is the major risk factor for the development of CVD (cardiovascular diseases). This is attributable, in part, to the development of vascular endothelial dysfunction, as indicated by reduced peripheral artery EDD (endothelium-dependent dilation) in response to chemical [typically ACh (acetylcholine)] or mechanical (intravascular shear) stimuli. Reduced bioavailability of the endothelium-synthesized dilating molecule NO (nitric oxide) as a result of oxidative stress is the key mechanism mediating reduced EDD with aging. Vascular oxidative stress increases with age as a consequence of greater production of reactive oxygen species (e.g. superoxide) without a compensatory increase in antioxidant defences. Sources of increased superoxide production include up-regulation of the oxidant enzyme NADPH oxidase, uncoupling of the normally NO-producing enzyme, eNOS (endothelial NO synthase) (due to reduced availability of the cofactor tetrahydrobiopterin) and increased mitochondrial synthesis during oxidative phosphorylation. Increased bioactivity of the potent endothelial-derived constricting factor ET-1 (endothelin-1), reduced endothelial production of/responsiveness to dilatory prostaglandins, the development of vascular inflammation, formation of AGEs (advanced glycation end-products), an increased rate of endothelial apoptosis and reduced expression of oestrogen receptor α (in postmenopausal females) also probably contribute to impaired EDD with aging. Several lifestyle and biological factors modulate vascular endothelial function with aging, including regular aerobic exercise, dietary factors (e.g. processed compared with non-processed foods), body weight/fatness, vitamin D status, menopause/oestrogen deficiency and a number of conventional and non-conventional risk factors for CVD. Given the number of older adults now and in the future, more information is needed on effective strategies for the prevention and treatment of vascular endothelial aging.
Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA. seals@colorado.edu
Douglas R
DR
Seals
Kristen L
KL
Jablonski
Anthony J
AJ
Donato
D000375:Aging / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology*; D015444:Exercise / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D009569:Nitric Oxide
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