Mini Review
Aging: A revisited theory based on free radicals generated by NOX family NADPH oxidases

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Abstract

Reactive oxygen species (ROS), often also referred to as free radicals, play an important role in aging. It is widely assumed that mitochondria are the predominant source of ROS relevant for the aging process. In this hypothesis article, we suggest that the role of ROS generated by NOX family NADPH oxidases has been largely overlooked in aging theories. NOX NADPH oxidases form a seven member gene family and are high level ROS-generating enzymes. As opposed to mitochondria, which generate ROS as a byproduct of their metabolism, NOX enzymes are professional ROS generators. From an experimental point of view, there is now abundant evidence for the involvement of NOX enzymes in age-associated diseases. The role of NOX enzymes in the aging process itself and their relative contribution as compared to mitochondria needs further investigations.

Section snippets

Introduction: a short history of reactive oxygen species (ROS) and aging

This hypothesis article is based on two, initially unrelated lines of scientific investigation: (i) designed ROS generation by NOX family NADPH oxidases and (ii) role of ROS in the aging process. Interestingly, the evidence for the existence of designed ROS-generation by NADPH oxidases precedes the concept that ROS are involved in aging. Indeed, the first description of a so-called respiratory burst, i.e. a massive use of oxygen by cells dates back to 1908, when Otto Warburg studied

NOX enzymes

NOX family enzymes are transmembrane electron transporters. They transport electrons from the cytoplasmic electron donor NADPH to molecular oxygen. This process leads to generation of superoxide. Depending on the localization of the respective NOX enzymes (plasma membrane versus intracellular organelles), this superoxide generation occurs either on the outside of the plasma membrane or within the lumen of organelles. However, ROS generated by NOX family NADPH oxidases are able to reach the

Contribution of NOX enzymes to age-related pathologies

As discussed in the chapter above, NOX enzymes have important physiological functions and a complete absence of NOX-dependent ROS generation is therefore detrimental for our organism. The question of this review is however different, namely: do NOX-derived ROS contribute to aging and age-related pathologies? In this chapter, I will summarize our present knowledge on the role of NOX-derived ROS in some relevant age-associated diseases.

Aging and ROS

As discussed in the last chapter, there is little doubt that NOX enzymes are important in the pathogenesis of age-associated diseases. However are they important for the aging process itself? The distinction between age-associated diseases and aging is not always obvious, but it is dear to many researchers in the aging field. It is based on the consideration that even if an old person does not develop Alzheimer’s disease, cardiovascular disease, osteoporosis etc., the person is still old. Thus,

Acknowledgement

This work was supported by a grant from the Swiss National Science Foundation.

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