Pathogenesis of Aging

Pathogenesis of Aging

Aging is commonly defined as the accumulation of diverse deleterious changes occurring in cells and tissues with advancing age that are responsible for the increased risk of disease and death. Aging changes can be attributed to developmental and genetic defects, the environment, disease processes, and an inherent process referred to as the “aging process” (Harman, 2003). The major theories of aging are all specific of a particular cause of aging, providing useful and important insights for the understanding of age-related physiological changes (Tosato, Zamboni, Ferrini & Cesari, 2007).

More than 300 theories have been proposed to explain the aging process, but none has yet been accepted by gerontologists (Tosato et al., 2007). The major theories of aging include: The free radical theory, the immunologic theory, the inflammation theory and the mitochondrial theory.

The free radical theory of aging was first formulated by Harman, who proposed that aging is due to the harmful activities of free radicals endogenously formed during normal metabolic processes (Harman, 1957). This theory was revised when mitochondria were identified as being responsible for the initiation of most of the free radical reactions relating to the aging process and life span (Harman, 1972). These reactions result in the formation of various reactive oxygen species (ROS) in the mitochondria of all tissues. This theory is being openly challenged by many (Lapointe & Hekimi, 2010).

The mitochondrial theory of aging is thought to involve damage to and mutations in Mitochondrial DNA (mtDNA) by an age-related increase in ROS, leading to primary (alteration of genes encoding subunits of the electron transport chain (ETC)) and secondary (all other mutations effecting the ETC) ETC protein defects causing dysfunction and enhanced ROS production. Enhanced ROS production further exacerbates the damage to mtDNA, perpetuating

the cycle (Johnston, De Lisio & Parise, 2008)....