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Free radicals, the relationship between apoptosis and aging Research


Senescence (aging) is the natural process of life and movement, there is no life at any time in the body, but under different circumstances the rate and extent of the difference. This major topic of aging is still limited to some preliminary understanding of experiments and theory, in which oxygen free radicals, and apoptosis affect the more far-reaching theory. In recent years, a large number of studies have shown: free radicals, especially oxygen free radicals involved in the regulation of apoptosis is one important factor, while others think this is essentially the death of aging cells apoptosis 〔1〕. Study of free radicals, apoptosis associated with aging, has important theoretical and practical significance. Chinese papers League finishing. 1 free radicals and apoptosis 1.1 derived free radicals and oxygen free radicals Free radicals are atoms with unpaired electrons, atoms and molecules, is redox reactions in the body's most important and most extensive response elements. In vivo generation and scavenging free radicals with a set of balance system, excessive production can cause varying degrees of cytotoxicity and instantaneous irreversible damage 〔2〕, are widely involved in aging, degenerative diseases, the incidence of cancer and other 〔3〕; antioxidant defense system to prevent oxygen and its metabolites on the toxicity of the body to maintain its state of balance is an important decision factor in cell survival. 1.2 Apoptosis Apoptosis is a multi-cellular organisms to maintain their own organizational stability, regulation of cell proliferation and death of their own balance between the initiative by the genetic control of cell death process 〔4 〕. Confirmed the main features of apoptosis: cell size smaller, condensed chromatin, dense staining area was massive, DNA molecules are specific DNA endonuclease cut between nucleosomes, nuclear cleavage, formation of apoptotic bodies, were phagocytic cells has cleared. DNA of apoptotic cells by agarose gel electrophoresis showed a difference of 180 ~ 220 pb ladder size map. Individual development is closely related with cell apoptosis, the body growth and aging are inseparable from the regulation of apoptosis, a variety of factors involved in the regulation of apoptosis process. 1.3 Free Radical apoptosis inducement of apoptosis in many in vivo metabolism or exogenous factors that produce free radicals were shown to induce apoptosis 〔5〕. Ionizing radiation is an important factor to induce apoptosis is one of the water molecules produced by direct radiation hydroxyl radical causes oxidative damage to cellular macromolecules, protein oxidation, DNA strand breaks, cell membrane from the shell, lipid oxidation, and These are precisely the characteristics of apoptosis. But not caused by hydroxyl free zone electrophoresis in apoptotic DNA ladder was the direct cause of 〔2〕,[link widoczny dla zalogowanych], it early apoptotic DNA fragments were cut into base related to the process. Free radicals can directly induce apoptosis, Lennon and other hematopoietic cells of 4 different HL60, U937, Molt-4 and Daudi were cultured in vitro and found that reactive oxygen species (ROS) directly induce apoptosis, the mechanism may be caused by ROS Ca2 + influx. Many different cell lines were exposed to a dose of 10 ~ 100 mmol / L hydrogen peroxide, can induce cell apoptosis 〔2〕; in 1 ~ 10 mmol / L dose of hydrogen peroxide, the performance The role of mitogen to stimulate cell growth; doses greater than 100 mmol / L, the performance of cytotoxicity; to 400 mmol / L, the direct result of cell necrosis. The different doses of hydrogen peroxide associated with cell growth state, suggesting that the quantitative role of free radicals on cell apoptosis have a major impact. nitric oxide (NO) is a free radical, with a single unpaired electron, the chemical properties of a very lively, with molecular oxygen to form oxygen free radicals and hydrogen peroxide. NO has been used as macrophages, monocytes, apoptosis-inducing agent 〔6〕, endogenous and exogenous NO can lead to increased apoptosis, the reason may be the result of direct damage to DNA cells . activity of reactive oxygen species is a highly non-specific molecules, regulation of apoptosis, mediated by apoptosis, which has been confirmed by many scholars from a variety of ways. Tumor necrosis factor (TNF) can induce production of intracellular oxygen, Mn-SOD expression in cells can inhibit TNF induced apoptosis. Tory and other 〔7〕 by specific inhibition of PC12 nerve cell line Cu-Zn-SOD in the synthesis experiment, SOD activity decreased proof can lead to apoptosis, which is a ROS-induced apoptosis. The results of HIV infection suggest that intracellular SOD, catalase decreased apoptosis may lead to 〔8〕. Many antioxidant substances can block apoptosis. Hockenbery et al 〔9〕 found that overexpression of glutathione peroxidase (GSH-Px) mouse IL-3 dependent FL5, FL12 cells lacking IL-3 in the case of survival. Others found that overexpression of Mn-SOD in tumor cells can tolerate radiation, anticancer drugs caused apoptosis. Although ROS can induce apoptosis, but not necessary for apoptosis substances, such as the cell culture in the anaerobic environment, reactive oxygen species can not be generated, but apoptosis was still occurring 〔10〕. closely associated with apoptosis gene bcl-2 was confirmed by adjusting the range of antioxidant pathway to prevent apoptosis induced by oxidative stress. It can prevent apoptosis induced by γ-ray 〔8〕, γ-ray ionization of water through the formation of DNA damage caused by reactive oxygen species, bcl-2 in the intracellular organelles of oxygen radical production, such as mitochondria, endoplasmic reticulum, nuclear membrane, etc., which indicated that bcl-2 is produced by ionizing radiation by inhibiting lipid peroxidation of ROS exert its function of inhibiting apoptosis. Another view, bcl-2 anti-apoptosis as a possible mechanism of free radical scavengers, such as most of the hydroxyl group in the body due to oxygen free radicals, hydrogen peroxide, Fe2 + concentration on specific sites, bcl-2 can reactive oxygen species produced in specific parts of antioxidant pathway to regulate 〔9〕. As noted above, the process of apoptosis involvement of free radicals, but the mechanism of free radical regulation of apoptosis is not clear, it was suggested two possible mechanisms 〔11〕: ① apoptotic factors can make hydrogen peroxide (H2O2) levels, H2O2 and then activate the death gene Ced-3, etc., so that programmed cell death. ② factors can cause apoptosis activate Ced-3 and other death gene, which raise the level of intracellular H2O2, the effect of H2O2 damage to cell death. 2 cell apoptosis and aging 2.1 Biology of aging people to death from the embryo to the body throughout the life course happened over time the formation of degenerative changes over the property of belonging to aging. Usually talked about aging is that organisms in the life course, with age, the morphological structure and physiological function to a series of chronic, progressive, degenerative changes. These changes result in adaptation, declining reserves of power, the ongoing development of this process, the formation of aging. French embryologist Minot that aging is the result of cell differentiation; 19th century WEismann the hypothesis that aging is a form of adaptation according to the procedure, is evolution occurred; evolutionary theory of aging is derived from the experts believe that with the selective pressure age decreased. With the improvement of analytical methods and techniques, many changes in gene expression in senescent cells was clear that the resulting genetic program hypothesis that the cells from the active role of aging process and cause morphological changes characteristic of growth arrest and senescence that senescent cells Real death is apoptosis 〔1〕. 2.2 apoptotic effects of aging cells in the body of many important physiological and pathological processes, but people on the mechanism of apoptosis and senescence is still not very clear, both in research are related, their common view is that cells can not be replaced by destroying important cells from the negative effects of aging, proposed in two forms of apoptosis of aging work 〔12〕: ① has been damaged and removed cell dysfunction (such as liver cells, fibroblasts), by fibrous tissue replacement and continue to maintain homeostasis; ② clear cells can not regenerate (such as neurons, cardiac cells), they can not be replaced, resulting in pathological changes. Through the above mechanism, resulting in apoptosis of somatic cells, especially those with important functions of cells, such as reduction in the number of brain cells, causing the composition of their vital organs such as the brain cortex atrophy senile progressive pathological process. 3 radicals, apoptosis and aging As mentioned earlier, free radicals and apoptosis are closely related. Consider that the oxygen free radicals by cell apoptosis is an important factor in the aging process. Clear oxygen free radicals produced enzymes to reduce free radicals, have anti-aging effect, on the contrary, increased reactive oxygen species, or the decrease of antioxidants leads to apoptosis, may promote the aging process. Rusting 〔13〕 had to develop a life of almost twice the wild-type flies, and found that long-lived Drosophila SOD activity is high. Appropriate diet, the body reduces the load of oxygen, oxygen free radicals reduce the impact of the minimum exchange of DNA bases, single strand breaks, inhibition of the apoptosis can be appropriate, to delay age-related changes, many physiological, biochemical, behavioral changes in the aging delay and, ultimately, longer life.