Healthy aging regulation of the metabolome by cel

Authors: Anthony William Linnane Michael Kios Luis Vitetta

Publish Date: 2007/04/06

Volume: 8, Issue: 5, Pages: 445-467

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Abstract

The production of reactive oxygen species ROS and reactive nitrogen species RNS has long been proposed as leading to random deleterious modification of macromolecules with an associated progressive development of age associated systemic disease ROS and RNS formation has been posited as a major contributor to the aging process On the contrary this review presents evidence that superoxide anion and hydrogen peroxide and nitric oxide and peroxynitrite constitute regulated prooxidant second messenger systems with specific subcellular locales of production and are essential for normal metabolome and physiological function The role of these second messengers in the regulation of the metabolome is discussed in terms of radical formation as an essential contributor to the physiologically normal regulation of subcellular bioenergy systems proteolysis regulation transcription activation enzyme activation mitochondrial DNA changes redox regulation of metabolism and cell differentiation the concept that orally administered small molecule antioxidant therapy is a chimera The formation of superoxide anion/hydrogen peroxide and nitric oxide do not conditionally lead to random macromolecular damage under normal physiological conditions their production is actually regulated consistent with their second messenger roles

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