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发布于:2020-11-27 13:14:07  访问:1 次 回复:0 篇
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One important factor in longevity appears to be basal metabolic rate, which is much lower in man than in rodents and could markedly affect the level of endogenous mutagens produced by normal metabolism.Two products of oxidative damage to DNA are thymine glycol and hydroxymethyluracil.The existence of these specific repair enzymes points to the importance of this type of DNA damage in vivo.Ourmethod suffers from being an indirect measurement of what was in the D N A and being potentially subject to artifacts.Thls total may there fore represent anaverage of about oxidized thymine residues per day for each of the bodys x cells.The faster rate of aging and the faster accumulation of carcinogenic events for mamma ls with higher specific metabolic rates may be ex plained by assuming that these species have hlgher ra tes ofproduction of ox idan ts perceJ, leadingto faster accumulation of somatic damage, carcino genic events and a pin. We now havedata on species that provide addit ionalcircumstantial evi dence forthstheory and are consistent with the possibility that D N A is a critical target in aging. D ata ob tained with monkeys a re consistent withthsrela tionship. We have now tested urines for thymine glycol and thymidine glycol from no rmalhuman volun teers aged vears. The preliminary evidence is that their urinary outputs O X Y G E N C O N S U M P T I O N and thymdne glhcol for differentspecies, espressed ar a function of thespec fcmetabolic ra te. Th is is consistent with age independentsomatic damage theories of aging. Th is new assav canbedone quickly and thus will enable a much more rapid and simpler assay of urine for oxidized D N A. This is evidence that the presence of oxidized D N A bases in urine is not a consequence of normal cell turnover. Itis present at a level of bases in nuclear D N A and bases in mitochondrial DNA. The ex tremely high level in mitochondria D N A may be caused by the immense oxygen metabolism, rela tively inefficient D N A repair and the absence of histones inmi tochondria. Thusmitochondria may be accumulating mu tations with age which could Targetmol‘s Dolasetron cornpronlise energy supplies to the cell.A new method for the analysis of mG adducts has been devel oped by combining the selectivity of separation of reversedphase highperformance liquid ch ro matography with the specificity and high sensitiv ity of glectrochemigal detectioo. The sensitivity of the method is about fold that of optical methods and is suffi cient to determine the endogenous background of DNA methylation.DNA from the liver of normal young rats containsm. Since mG is only one of about deleterious methylation adducts, the true steadystate level of all adducts should be higher.Uric acid is the main antioxidant in saliva and is pM in human blood.Itis present in much lower amounts in animals before the primates.Heme is degraded tohiliuerdis and in mammals biliverdin is converted to bilirbi bo th of which are shown to be powerful antioxidants. Thebi lirubin in human blood is bound at a specific site on albumin at a concentration of pM.
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