Genetic stability and oxidative stress: common mechanisms in aging and cancer.
Much evidence indicates that age-related diseases as well as the aging process itself may be a result of genetic instability, resulting in cells changing their proper state of differentiation. Such genetic changes could be of an epigenetic or genetic nature (or both) and suggest that mechanisms acting to stabilize the differentiated state of cells could be major determinants of animal species' general health and longevity. There is also much data indicating that a causative factor in cancer is genetic instability, suggesting the importance of genetic stabilized factors governing the frequency of this disease. Possibly related to these two observations is the good positive correlation between rate of cancer and the rate of aging of different mammalian species. In addition, cells from longer-lived species appear to have a higher intrinsic ability to maintain their proper differentiated state and animals whose life span has been extended by food restriction also have a postponed onset of cancer. These data suggest the possibility that genetic instability may represent a common causative mechanism for both aging and cancer. This suggestion is supported by evidence indicating that oxidative stress can increase cancer frequency and that longer-lived species appear to have a lower oxidative stress state. However, there appears to be a serious lack of evidence indicating that physical and chemical mutagenic agents accelerate aging as they do cancer. For these and other considerations, it is proposed that aging is not a result of genetic instability as are many different age-related diseases. Thus, physiological aging and some age-related diseases could have separate and distinct mechanisms of causation and control.
Cutler
R G
RG
Gerontology Research Center, National Institute on Aging, Baltimore, MD 21224.
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D005609:Free Radicals; D015186:Hominidae / Q000235:genetics; D006801:Humans; D008136:Longevity / Q000235:genetics; D009369:Neoplasms / Q000209:etiology / Q000503:physiopathology*
D000975:Antioxidants; D005609:Free Radicals