PH OF CULTURE MEDIUM AND STATIONARY PHASE/CHRONOLOGICAL AGING OF DIFFERENT CELLS

There is a point of view that the chronological aging (CA) of yeast and the stationary phase aging (SPA) of cultured animal and human cells are a consequence of growth medium acidification. However, a number of recent publications indicate that the process influences, to a certain extent, on the rate of “aging” of cells in the stationary phase of growth but does not determines it completely. Apparently, the key factor in this case is the cell proliferation restriction which leads to “aging” of the cells even under physiologically optimal conditions. During yeast CA and SPA of mammalian cells the medium is getting acidified to pH≤4. Preventing the medium acidification could make it possible to increase the culture life span, but the cells will still die out, albeit at a slower rate. Effects of the medium acidification observed during CA and SPA can be explained by the activation of highly conserved growth signaling pathways leading to the oxidative stress development; these processes, in turn, can be involved in aging of multicellular organisms and play a role in their age-related diseases. A while ago we studied the effect of buffer capacity of growth medium on SPA of transformed Chinese hamster cells. We found that HEPES at 20 mM had no effect on the cell growth, and both control and experimental growth curves reached plateau level on the same day. However, the cells grown with HEPES, on the one hand, reached lower saturation density than the control ones (i.e., were “older” in terms of the gerontological cell kinetics model), and on the other – underwent SPA at much slower rate (though still were “getting older”). It can be assumed that extracellular pH which, by the way, is well correlated with intracellular pH, is very important (I.A. Arshavsky’s concept on a role of the acidic alteration in aging) but not the key factor determining survival of cells in a stationary culture.

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