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The free radical theory of aging (FRTA) states that organisms age because cells accumulate free radical damage over time.〔Hekimi S, Lapointe J, Wen Y. Taking a "good" look at free radicals in the aging process. Trends In Cell Biology. 2011;21(10) 569-76.〕 A free radical is any atom or molecule that has a single unpaired electron in an outer shell.〔Erbas M, Sekerci H. IMPORTANCE OF FREE RADICALS AND OCCURRING DURING FOOD PROCESSING. SERBEST RADÏKALLERÏN ONEMÏ VE GIDA ÏSLEME SIRASINDA OLUSUMU. 2011;36(6) 349-56.〕 While a few free radicals such as melanin are not chemically reactive, most biologically-relevant free radicals are highly reactive.〔Herrling T, Jung K, Fuchs J. "The role of melanin as protector against free radicals in skin and its role as free radical indicator in hair. ''Spectrochimica Acta Part A: Molecular & Biomolecular Spectroscopy.'' 2008;69(5) 1429-35.〕 For most biological structures, free radical damage is closely associated with oxidative damage. Antioxidants are reducing agents, and limit oxidative damage to biological structures by passivating them from free radicals.〔Halliwell B. "Free radicals and antioxidants: updating a personal view. ''Nutrition Reviews.'' 2012;70(5) 257-65.〕 Strictly speaking, the free radical theory is only concerned with free radicals such as superoxide ( O2− ), but it has since been expanded to encompass oxidative damage from other reactive oxygen species such as hydrogen peroxide (H2O2), or peroxynitrite (OONO−).〔 Denham Harman first proposed the free radical theory of aging in the 1950s, and in the 1970s extended the idea to implicate mitochondrial production of reactive oxygen species. In some model organisms, such as yeast and ''Drosophila'', there is evidence that reducing oxidative damage can extend lifespan.〔Fontana L, Partridge L, Longo VD. Extending Healthy Life Span—From Yeast to Humans. Science. 2010 April 16, 2010;328(5976) 321-6.〕 In mice, interventions that enhance oxidative damage generally shorten lifespan.〔Pérez VI, Bokov A, Remmen HV, Mele J, Ran Q, Ikeno Y, et al. Is the oxidative stress theory of aging dead? Biochimica et Biophysica Acta (BBA) - General Subjects. 2009;1790(10) 1005-14.〕 However, in roundworms (''Caenorhabditis elegans''), blocking the production of the naturally occurring antioxidant superoxide dismutase has recently been shown to ''increase'' lifespan. Whether reducing oxidative damage below normal levels is sufficient to extend lifespan remains an open and controversial question. == Background == The free radical theory of aging was conceived by Denham Harman in the 1950s, when prevailing scientific opinion held that free radicals were too unstable to exist in biological systems.〔Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956 Jul;11(3) 298-300.〕 This was also before anyone invoked free radicals as a cause of degenerative diseases.〔Harman D. Origin and evolution of the free radical theory of aging: a brief personal history, 1954–2009. Biogerontology. 2009;10(6) 773-81.〕 Two sources inspired Harman: 1) the rate of living theory, which holds that lifespan is an inverse function of metabolic rate which in turn is proportional to oxygen consumption, and 2) Rebbeca Gershman's observation that hyperbaric oxygen toxicity and radiation toxicity could be explained by the same underlying phenomenon: oxygen free radicals.〔〔Speakman JR, Selman C. The free-radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan" ''BioEssays'' 2011;33(4) 255-9.〕 Noting that radiation causes "mutation, cancer and aging", Harman argued that oxygen free radicals produced during normal respiration would cause cumulative damage which would eventually lead to organismal loss of functionality, and ultimately death.〔〔Speakman JR, Selman C. The free-radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan" ''BioEssays'' 2011;33(4) 255-9.〕 In later years, the free radical theory was expanded to include not only aging ''per se'', but also age-related diseases.〔 Free radical damage within cells has been linked to a range of disorders including cancer, arthritis, atherosclerosis, Alzheimer's disease, and diabetes.〔Clancy D, Birdsall J. Flies, worms and the Free Radical Theory of ageing. Ageing Research Reviews. (0).〕 There has been some evidence to suggest that free radicals and some reactive nitrogen species trigger and increase cell death mechanisms within the body such as apoptosis and in extreme cases necrosis.〔Chatterjee S, Lardinois O, Bhattacharjee S, Tucker J, Corbett J, Deterding L, et al. Oxidative stress induces protein and DNA radical formation in follicular dendritic cells of the germinal center and modulates its cell death patterns in late sepsis. Free Radical Biology and Medicine. 2011;50(8) 988-99.〕 In 1972, Harman modified his original theory to what became known as the mitochondrial theory of aging.〔 In its current form, this theory proposes that reactive oxygen species that are produced in the mitochondria, causes damage to certain macromolecules including lipids, proteins and most importantly mitochondrial DNA.〔Jang YC, Remmen HV. The mitochondrial theory of aging: Insight from transgenic and knockout mouse models. Experimental Gerontology. 2009;44(4) 256-60.〕 This damage then causes mutations which leads to an increase of ROS production and greatly enhances the accumulation of free radicals within cells.〔Jang YC, Remmen HV. The mitochondrial theory of aging: Insight from transgenic and knockout mouse models. Experimental Gerontology. 2009;44(4) 256-60.〕 This mitochondrial theory has been more widely accepted that it could play a major role in contributing to the aging process.〔Gruber J, Schaffer S, Halliwell B. The mitochondrial free radical theory of ageing--where do we stand? Frontiers in bioscience : a journal and virtual library. 2008;13:6554-79.〕 Since Harman first proposed the free radical theory of aging, there have been continual modifications and extensions to his original theory.〔Gruber J, Schaffer S, Halliwell B. The mitochondrial free radical theory of ageing--where do we stand? Frontiers in bioscience : a journal and virtual library. 2008;13:6554-79.〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Free-radical theory of aging」の詳細全文を読む スポンサード リンク
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