A membrane hypothesis of aging

Abstract

Experimental data show that cell membranes become more rigid during aging. If this involves a decrease of resting potassium permeability, the intracellular potassium concentration will increase. Such an increase is beneficial for the maintenance of cell excitability, however, it represents a drawback for the nuclear functions, since the intracellular ionic strength may reach values even above 400 mEq kg −1 cell water, where the chromatin becomes more condensed and the activity of DNA-dependent RNA-polymerase as well as other enzymes probably decreases. This “membrane hypothesis” of aging may explain the decreased protein synthetic activity of old cells, especially of postmitotic ones. X-ray microanalysis has revealed that potassium concentrations significantly increase in the nucleus and cytoplasm of brain and liver cells of old rats. The chromatin of old nerve cells is more condensed than that of the young ones, the rates of nucleolar and nucleoplasmic RNA-synthesis are significantly lower in the old brain cells, and also the number of perichromatin granules decreases with age. A decrease of intracellular potassium content, in brain cells of old rats can be brought about by phytohemagglutinin-P and centrophenoxine. This is accompanied by a sort of rejuvenation: the chromatin becomes decondensed, the rates of nucleolar and nucleoplasmic RNA-synthesis increase together with the number of perichromatin granules, the medium life-span and the learning capacity of the animals increase. These experimental results support the “membrane hypothesis” of aging.