Application of a molecular enzyme kinetic model for aging cells and tissues

According to the membrane hypothesis of aging (MHA), cellular senescence is attributable to a life-long, cross-linking action of oxygen-free radicals in the cell plasma membrane, resulting in a continuous decrease of the passive ion permeabilities. The consequent increase in the intracellular potassium content is accompanied by a considerable condensation of the intracellular mass (i.e., by loss of water). MHA suggested that an age-dependent increase in the physical density of the intracellular mass can underly the well-known age-dependent decreases of the macromolecular synthetic processes, the enzymic turnover rates, etc. MHA was partly based on a molecular enzyme kinetic model (MEKM) suggesting that environmental factors can substantially influence the enzyme catalysis and regulation through collisional coupling. However, the possible quantitative ranges of alterations in enzyme activities have not been estimated. This paper concludes, using principal features of the two models, that known age-dependent changes in the membrane lipid fluidity and intracellular density may result in even a 10-fold overall decrease in the enzyme activities (characterized by kcat and k-1) during the life.