The Free Radical Theory of Aging Matures

Abstract

The free radical theory of aging, conceived in 1956, has turned 40 and is rapidly attracting the interest of the mainstream of biological research. From its origins in radiation biology, through a decade or so of dormancy and two decades of steady phenomenological research, it has attracted an increasing number of scientists from an expanding circle of fields. During the past decade, several lines of evidence have convinced a number of scientists that oxidants play an important role in aging. (For the sake of simplicity, we use the term oxidant to refer to all "reactive oxygen species," including O2-., H2O2, and .OH, even though the former often acts as a reductant and produces oxidants indirectly.) The pace and scope of research in the last few years have been particularly impressive and diverse. The only disadvantage of the current intellectual ferment is the difficulty in digesting the literature. Therefore, we have systematically reviewed the status of the free radical theory, by categorizing the literature in terms of the various types of experiments that have been performed. These include phenomenological measurements of age-associated oxidative stress, interspecies comparisons, dietary restriction, the manipulation of metabolic activity and oxygen tension, treatment with dietary and pharmacological antioxidants, in vitro senescence, classical and population genetics, molecular genetics, transgenic organisms, the study of human diseases of aging, epidemiological studies, and the ongoing elucidation of the role of active oxygen in biology.

Plasma markers of oxidative stress are uncorrelated in a wild mammal

“…2009). ROS are primarily produced as by‐products of oxidation–reduction (redox) reactions (Beckman and Ames 1998; Dowling and Simmons 2009), which occur during aerobic metabolism within the mitochondria. They are important components of cellular signaling (e.g., Nemoto et al.…”

“…2000) and immune function (Babior et al. 1973; Forman and Torres 2002), but in excess can cause DNA, lipid, and protein damage and disrupt cellular function (Harman 1956; Beckman and Ames 1998; Buffenstein et al. 2008).…”

Phenyl 2‐pyridyl ketoxime induces cellular senescence‐like alterations via nitric oxide production in human diploid fibroblasts

“…The involvement of ROS in degenerative senescence has been proposed previously (Beckman & Ames, 1998; Haendeler et al ., 2003; Kurz et al ., 2004). To investigate the molecular mechanism for PPKO‐induced cellular senescence, we examined whether PPKO induces the accumulation of ROS in young HDFs.…”

“…The molecular changes associated with senescence‐like growth arrest depend on the chemicals used. According to the free‐radical theory of aging (Beckman & Ames, 1998; Haendeler et al ., 2003; Kurz et al ., 2004), reactive oxygen species (ROS) are potential candidates for senescence induction, and ROS‐induced oxidative stress may promote cellular senescence. Because ROS are highly reactive molecules, they can damage many cellular components, and thus, they are considered a probable cause of cellular senescence and degenerative aging.…”

Evidence that a mitochondrial death spiral underlies antagonistic pleiotropy

“…This possibility is supported by investigations by several groups (reviewed in Droge, 2003). In particular, older animals generate more oxidation products than younger animals in response to radiation (Beckman & Ames, 1998). In addition, levels of reduced glutathione decline with age both in plasma and in multiple tissues (Maher, 2005; Jones, 2006), perhaps as a consequence of age‐dependent decreases in glucose 6 phosphate dehydrogenase activity (Beckman & Ames, 1998).…”