%0 Journal Article
%T Oxidative Stress, Mitochondrial Dysfunction, and Aging
%A Hang Cui
%A Yahui Kong
%A Hong Zhang
%J Journal of Signal Transduction
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/646354
%X Aging is an intricate phenomenon characterized by progressive decline in physiological functions and increase in mortality that is often accompanied by many pathological diseases. Although aging is almost universally conserved among all organisms, the underlying molecular mechanisms of aging remain largely elusive. Many theories of aging have been proposed, including the free-radical and mitochondrial theories of aging. Both theories speculate that cumulative damage to mitochondria and mitochondrial DNA (mtDNA) caused by reactive oxygen species (ROS) is one of the causes of aging. Oxidative damage affects replication and transcription of mtDNA and results in a decline in mitochondrial function which in turn leads to enhanced ROS production and further damage to mtDNA. In this paper, we will present the current understanding of the interplay between ROS and mitochondria and will discuss their potential impact on aging and age-related diseases. 1. Introduction The fundamental manifestation of the aging process is a progressive decline in the functional maintenance of tissue homeostasis and an increasing propensity to degenerative diseases and death [1]. It has attracted significant interest to study the underlying mechanisms of aging, and many theories have been put forward to explain the phenomenon of aging. There is an emerging consensus that aging is a multifactorial process, which is genetically determined and influenced epigenetically by environment [2]. Most aging theories postulate a single physiological cause of aging, and likely these theories are correct to a certain degree and in certain aspects of aging. Reactive oxygen species (ROS) are highly reactive molecules that consist of a number of diverse chemical species including superoxide anion ( O 2 £¿ ), hydroxyl radical ( £¿ O H ), and hydrogen peroxide (H2O2). Because of their potential to cause oxidative deterioration of DNA, protein, and lipid, ROS have been implicated as one of the causative factors of aging [3]. As ROS are generated mainly as by-products of mitochondrial respiration, mitochondria are thought to be the primary target of oxidative damage and play an important role in aging. Emerging evidence has linked mitochondrial dysfunction to a variety of age-related diseases, including neurodegenerative diseases and cancer. Details of the precise relationship between ROS-induced damage, mitochondrial dysfunction, and aging remain to be elucidated. 2. ROS and Aging 2.1. ROS, Oxidative Damage, and Cellular Signaling There are several sources of ROS within a cell. ROS are generated as
%U http://www.hindawi.com/journals/jst/2012/646354/