The waste-product theory of aging: simulation of metabolic waste production.
A mathematical model of cellular metabolism is used to relate the rates of cell division and waste production to the concentrations of oxygen and glucose in the medium in which a normal diploid cell culture is grown. The metabolic model in tandem with an earlier waste-content model based on the waste-product theory of aging provides a unified cell-culture model with which population size and intracellular waste content can be calculated. Population size is measured by the number of population doublings which have been achieved. After suitable adjustment of parameters in the metabolic model, maximum values of population size are calculated numerically with the use of the unified model. Results show that the population maxima are related in a plausible way to the oxygen and glucose concentrations. The effects of temperature changes and contact inhibition of growth are also simulated. Small changes in the cell-division and waste-production rates can cause transformation to unlimited growth in the waste-content model, but the unified model is not correspondingly sensitive to changes in the oxygen and glucose concentrations or to changes in temperature.
Hirsch
H R
HR
Department of Physiology and Biophysics, College of Medicine, University of Kentucky, Lexington 40536-0084.
Witten
M
M
D002455:Cell Division; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D003260:Contact Inhibition; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D013696:Temperature
D005947:Glucose; D010100:Oxygen