Magnetic isotope effects and nuclear spin catalysis in living cells and biomolecular motors: recent advances and future outlooks: Nuclear spin catalysis.

Biomolecular nanoreactors are constructed from chemical elements many of which have magnetic and nonmagnetic stable isotopes. The magnetic isotope effects (MIE) were discovered in experiments with the cells enriched with different isotopes of magnesium, magnetic or nonmagnetic ones. The striking catalytic effect of the magnetic isotope, 25Mg, was revealed in the reaction of ATP hydrolysis driven by myosin, the biomolecular motor utilizing the chemical energy of ATP to perform the mechanical work. The rate of the enzymatic ATP hydrolysis with 25Mg as the enzyme cofactor is twice higher than the rates of the reactions with nonmagnetic 24Mg or 26Mg. A similar effect of the nuclear spin catalysis was revealed in the experiments with zinc as the myosin cofactor. MIE unambiguously indicate that, in the chemo-mechanical process catalyzed by the molecular motor, there is a limiting step which depends on the electron spin state of the reagents, and this step is accelerated by the nuclear spin of the magnetic isotope. The recent developments in this field highlight promising venues for future research of MIE in biophysics with possible applications of the magnetic isotopes in medical physics including radiation medicine and biomedical effects of electromagnetic fields.

Free Radical Timer of Aging: from Chemistry of Free Radicals to Systems Theory of Reliability.

There are two generally known concepts in biology of aging. Accordingly to the first one, there is a program of aging. The alternative concept advocates that aging proceeds stochastically. In this area of research, free radical-theory of aging, which was put forward by Denham Harman in fifties of XXth century, has determined the most heuristic line. The goal of this review is to demonstrate how the aging program and the aging stochastics are united on the basis of the systems theory of reliability. On this basis, universal features of aging, such as the exponential growth of mortality rate with time and correlation of longevity with the species-specific resting metabolism, are naturally explained. The stochastic malfunctions of the mitochondrial electron transport nanoreactors, which produce the oxygen anion-radicals (O2•-) as by-products of respiration, seem to be of first importance. As a reducing agent, O2•- affects the ratio of NAD(P)H/NAD(P)+ and, by changing the activity of sirtuins, slows down renewal of biomolecular constructs. As a consequence, the oxidative-stress products and other metabolic slag accumulate with the resulting impetus to autophagic or apoptotic cell death accompanied with age-associated clinical disorders. Based on this reliability-theory approach, one can estimate that the longevity of human brain could reach 250 years should the antioxidant defense against the free-radical failures be perfect. Thus, the free-radical redox timer serves as effective stochastic mechanism of realization of the programmed deficiency in reliability of biomolecular constructs.

Correlation between activity of antioxidant enzymes and circadian rhythms of corticosteroids in Macaca mulatta monkeys of different age.

Young rhesus monkey females (Macaca mulatta) demonstrate the well-defined circadian rhythm in activity of erythrocyte SOD with maximum at 10.00 h and minimum at 22.00 h. However, neither GSH-Px nor GR demonstrated any significant circadian changes, contrastingly to SOD. The diurnal changes in the SOD activity tightly correlate with the diurnal changes in the levels of cortisol and DHEAS in the animals' blood plasma. With aging, these circadian rhythms of SOD, cortisol and DHEAS are smoothed out although the correlation between the diurnal changes in cortisol and SOD still maintains even for old animals. These results suggest that corticosteroids play an essential role in regulation of the SOD activity and that the reliability of the hormonal regulation decreases with aging.