ИСТИНА

Direct relationship between ageing and development was assumed by many gerontologists. However, the relationship can be of two kinds: 1) the program of development is simultaneously the program of ageing; 2) ageing is only a "byproduct" of development. I also think that there is no program of ageing and the development program bringing an organism which is capable of ageing (we cannot ignore the existence of non-aging species) to reproduction stops "taking care" of it and hereby promotes (without any malice!) subsequent increase of mortality rate with the lapse of time. Apparently, the course of events is the following (Khokhlov, 1983, 1988, 2000). Cell proliferation restriction in vivo, due to appearance in the process of differentiation of cell populations with low or zero proliferative activity, leads to sharp (10- or even 100-fold!) decrease of average cell replication rate in the organism. It induces the process of increase with time of average number of "senile" macromolecular damage (most probably, DNA damage) per cell. This accumulation does not take place in the populations consisting from fast proliferating cells because "young" cells arising after cell division do not have the defects (or have only a few of them). It leads to persistent "dilution" of existing or newly arising defects. The "senile" DNA damage (it is assumed that they are not mutations but physico-chemical defects incompatible with DNA replication or inducing serious chromosome aberrations leading to cell death) appear spontaneously in any cell under treatment of different chemical and physical factors (free radicals, ionizing radiation, heat movement of molecules, a.o.) and later can be eliminated by DNA repair system, disappear together with dying cell or remain in non-dividing cell increasing the defects' "load" in the cell population. The accumulation of DNA damage in tissues and organs manifests in their function changes, arising of different "age" diseases and, finally, increase of the organism's death probability, i.e. senescence. It is necessary, however, to emphasize that we do not consider proliferation restriction as the primary cause of ageing. Naturally, no one organism ages because of slowing down proliferation of its cells. It ages because of accumulation of DNA damage due to cell proliferation restriction. Thus, the primary cause of ageing is exactly the accumulation of DNA damage since it necessarily leads to functional impairment and increase of organism's death probability. One can easily imagine the situation when, with the help of some factor, even in non-dividing (or dividing very slowly) cells the accumulation of DNA damage is stopped or DNA repair is activated. Therefore it is reasonable to ask why investigations on stationary cultures (the "stationary phase ageing" model we elaborated) are beneficial for experimental gerontology. The answer seems to us obvious: with the help of the model we can discover the concrete character of "senile" DNA damage in cell population and peculiarities of their accumulation. Besides, the model gives the possibility of express testing of different physical and chemical factors which could retard (or, ideally, fully stop) the accumulation. The author is grateful to Russian Basic Research Foundation for support (grant 00-04-48049).