New directions for studying the role of free radicals in aging

Abstract

Oxidative damage caused by free radicals in vivo is believed to play an important role in the etiology of aging and age-associated degenerative diseases. The most direct evidence supporting this theory is the recent finding that the transgenic Drosophila that overexpress the antioxidant enzymes catalase and superoxide dismutase exhibit an increase in life span. Although the increase in life span in Drosophila by these enzymes is certainly important, the next logical direction is to demonstrate whether increased antioxidant protection occurs similarly in mammals. Several transgenic mouse models that overexpress antioxidant enzymes are currently available. However, one major shortcoming in using these transgenic mice is the difficulty of producing antioxidant overexpression in more than a few tissues. Despite the potential shortcomings of using transgenic mice, these animals provide a unique system in which individual components of a complex system, such as the antioxidant defense system, can be modulated and examined independently. Transgenic mice are therefore potentially powerful tools to study the role of various components of the antioxidant system in the aging process.A parallel direction in the study of free radical roles in aging is to investigate the modulation of transcription factors by oxidative stress. Among these, the transcription factors, NF-KB and AP-1 are implicated in oxidative stress. The activities of these oxidative stress-response transcription factors are regulated by upstream signaling molecules, which involve a cascade of phosphorylation and dephosphorylation events leading to their activation. In this article, we review recent studies that use molecular approaches to investigate the biological role of oxidant stress. Each of these studies potentially provide new insights into the roles of free radicals and free radical damage in the aging process.

Aging in a dish: Age‐dependent changes of neuronal survival, protein oxidation, and creatine kinase BB expression in long‐term hippocampal cell culture

“…Several lines of evidence suggest that aging is associated with increased intensity of oxidative damage (Stadtman, 1992;Sohal and Orr, 1998), and evidence accumulates that oxygen radicals play a role in degenerative senescence of the nervous system (Harman, 1995;Pahlavani and Van Remnen, 1997;Markesbery, 1997). One of the hallmarks of age-related cumulative oxidative damage is the accumulation of ''terminally marked'' proteins in aging tissues (Stadtman and Berlett, 1998;Gracy et al, 1998).…”

Xy99-5038 Promotes Long-Term Survival of Cultured Retinal Neurons

“…The overall evidence indicates differentiated cells in vivo accumulate damage over lifetime that results in gradual loss of function and increased probability of degeneration (Rubin, 1997;Drachman, 1997). It has been demonstrated that aging is associated with increased intensity of oxidative damage (Stadtman, 1998;Sohal & Orr, 1998), and that oxygen radicals plays a role in degenerative senescence of the nervous system (Herman, 1995;Pahlavani & Van Remnen, 1997;Markesbery, 1997). The attractive feature of the oxidative stress hypothesis is that it can account for cumulative damage associated with the delayed onset and progressive nature of aging-related disorders, such as Parkinson's disease and Alzheimer's disease as well as retinal degeneration (Carney, 2000;Beatty et al, 2000).…”

A Review on the Antioxidant and Therapeutic Potential of Bacopa monnieri

“…Potential biological damage occurs as a result of an overproduction of ROS and RNS and a down regulation of enzymatic and non-enzymatic antioxidants. The ROS generated by the powerful oxidizing agents interfere with the expression of a number of genes involved in the activation of signal transduction cascades [4][5][6][7] leading to important cellular events such as apoptosis. The reducing environment inside the cells aids prevention of free radical-mediated damage.…”