Aging Oxidative Stress and Prostate

Aging is associated with many metabolic disorders and with increased incidence of various cancers [50, 51]. Prostate cancer is a major age-related malignancy. Many theories have been formulated to explain the molecular and biochemical aspect of aging, but Harman in 1956 proposed "free radical theory of aging" in which the author suggested that the accumulation of damage to biomolecules caused by free radicals plays a major role in human aging [52, 53]. It is also believed that cellular oxidative stress increases with age and the increase in mitochondrial mutations can lead to further increase in ROS generation due to defective oxidative phosphorylation and electron transport [54]. Thus, it is possible that the increase in ROS leads to a self-perpetuating cycle with an ever-increasing oxidative challenge placed on the cells.

Moreover, most of the cells in the prostate tumor express the androgen receptor and respond to androgens at an early stage, to facilitate their growth. Age-related changes in the levels of androgens and ratios of other androgenic hormones and changes in the balance between the auto/paracrine growth stimulatory factors [55] such as insulin growth factor (IGF), epidermal growth factor (EGF), and nerve growth factor (NGF), and the growth inhibitory factors such as transforming growth factors-b (TGF-b) and IGF-binding proteins (IGFBPs) are implicated for abnormal prostatic growth [56-58]. Interestingly, physiological stimulation of androgen receptor has been shown to increase ROS production [59, 60].

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