Relationship between metabolic rate, free radicals, differentiation and aging: a unified theory.

Metabolic rate is a major factor governing the rate of aging in both homeotherms and poikilotherms and is inversely related to life span. Homeotherms exhibit stable basal metabolic rates and species-specific life spans. Conversely, in poikilotherms, both basal metabolic rate and life span vary greatly. Metabolic potential (total energy consumed/g/life span) is a species-specific characteristic in Homoetherms and poikilotherms. Length of life is dependent upon the rate at which this fixed metabolic potential is expended, that is, metabolic rate. Oxygen-free radicals produced by metabolism can cause molecular damage. Accumulation of lipofuscin granules, Schiff-base-like, fluorescent material and thiobarbituric acid-reactants, as well as increased exhalation of pentane with age are indicative of free, radical-induced molecular damage. Metabolic rate influences the rate of age-related changes. There is an overlapping compensatory balance between various components of the antioxidant defense system. The total antioxidant capacity of cells tends to decline with age. A dynamic equilibrium may exist between the rate of free radical generation and antioxidant levels. The establishment of this equilibrium is associated with differentiation. It is hypothesized that loss of the equilibrium between free radical generation and antioxidant defenses results in dysdifferentiation, aging and cancer.