[Biochemistry of lifespan extension]

A review of biochemical mechanisms underlying the known approaches to extension of lifespan and/or slowing down of ageing suggests that they all modify balances between generation of active oxygen and carbonyl species and the mechanisms that protect from their damaging effects or repair their consequences. A likely common target of the geroprotector effects of antioxidants, melatonin, and antidiabetic biguanides is the mitochondrial respiratory chain. In biological species that evolved through r-selection (nematodes, fruit flies, mice, and rats), the balance between anabolic/reproductive and self-maintenance/protective functions is the most significant modifiable factor of longevity and ageing. At the molecular level, the pivot of this balance is formed by the forkhead-type transfactors, whereas at the physiological level the balance is determined by dietary calories and physical activity via mechanism in which the central role is played by insuline-like peptides and, also, growth hormone and leptin or their functional analogs. In biological species that evolved through K-selection (higher primates, particularly humans), the latter balance is less important, and the biochemical factors of aging are more refracted through the higher regulatory systems, of which the most significant are catecholaminergic mechanisms of regulation of neuroendocrine-immune interrelationships and the circulatory system. This results in a decreased geroprotector potential of calory restriction and in an increased importance of the optimal physical activity. When these conclusions are compared with demographic data, it comes out that virtually all advances in gerontology may be reduced to maxims of healthy ageing known from extreme antiquity. Under optimal socioeconomic conditions, the chances to approach the documented world record of human longevity (122 years) may be increased by (not to mention getting rid of smoking and other abuses) high physical activity, adequate nutrition enriched in fresh fruits, optimism, and timely treatment of specific diseases. The most important bottleneck in the realization of these reserves is currently the public consciousness rather than the science.