A mitochondrial membrane hypothesis of aging

Recently it has been demonstrated that the loss of water during aging from rat liver and heart muscle tissue is solely due to water loss from the mitochondria. A hypothesis is presented here which shows the relation between free radical attack to, and water loss from, the mitochondria and the decreased energy availability in aged cells. According to it, water loss from the mitochondria is due to an increasing permeability of the inner mitochondrial membrane as a result of its changed composition and, therefore, decreasing osmotic reflexion coefficients for inorganic ions, mainly potassium. The water loss results in limited diffusion of intramitochondrial metabolites and, according to the theory of polyelectrolyte solutions, electrostatic and sterical hindrance of enzymic functions. The hypothesis is in accordance with the well-documented experimental facts, e.g. the lack of structural alterations in mitochondrial DNA and proteins, the constancy of the ?µH+ and the decrease of state 3 respiration with only a limited number of substrates in mitochondria from old postmitotic cells. © 1987 Academic Press Ltd.