V.K. Koltover

Despite the phenotypic variety, aging of all organisms is governed by the universal quantitative laws. First, each species is characterized by the species-specific maximal life-span potential. Second, the growth of mortality rate with age obeys to the statistics of extremes (usually, the Gompertz law of mortality, h(t) = ho exp(γt), where ho и γ are the time-independent parameters), that has been confirmed for people and for other species of mammals, flies, mollusks, etc. Third, the maximal life-span is inversely related to the resting metabolic rate (basal oxygen consumption) of the species ('Rubner scaling relation'). The universal theory of aging is based on the concept that all molecular biological constructions perform their functions with the genetically limited reliability (Blumenfeld & Koltover, 1972; Grodzinsky et al., 1987). This reliability-theory concept pieces together the hypotheses of free radicals (Harman, 1954), telomere 'circumcision' (Olovnikov, 1971), and adaptation-regulatory 'vitauct' (Frolkis, 1969) into the unified pattern (Koltover, 1983; 1997). Aging is ultimately caused by the time-dependent changes in the life-assurance genes (LAS) of a special pool of post-mitotic cells, which control the reliability of operation of the organisms defense systems. Longevity is determined by the programmed deficiency in the reliability of biomolecular constructions at all functional strata beginning with the molecular level of organization. The random malfunctions of mitochondrial respiratory chains are of the first importance since they produce toxic superoxide radicals. Since all defense systems (SOD, DNA-repair enzymes, etc.) operate with the limited reliability, stochastic irreparable damages accumulate up to the threshold dysfunction level in LAS, despite the compensating 'vitauct'. We estimated that the longevity of human brain could reach 250 years, should the reliability of mitochondrial SOD-defense be absolutely perfect. The harmful effects of ionizing radiation mainly arise from direct hits, i.e. - ionizations and excitations of atoms, inside LAS. When experimental animals are given single sublethal doses of ionizing radiation, chromosomes of the dividing cells occur to be mostly injured, entailing the critical shortage in redundancy of the functionally competent immune cells. On the Gompertz mortality functions, it shows up as the increase of ho while γ is unaltered. If irradiation occurs daily for the duration of life, the radiation-induced changes in LAS of the post-mitotic cells dominate, entailing the deterioration in performance of the defense systems. On the Gompertz functions, it shows up as the dose-dependent increase of γ while ho remains constant. The theory of reliability also provides an explanation for the hormetic effects of low doses of radiation.

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free radicals