The membrane hypothesis of aging: its relevance to recent progress in genetic research.

This review outlines the main concepts of the membrane hypothesis of aging (MHA) developed over the past two decades. MHA offers a general cell biological mechanism to explain the main trends of age-dependent changes in terms of intracellular physicochemistry. An essential point in MHA is that the inevitable plasma membrane alterations result in the accumulation of dry mass in the intracellular space, a process that is essential to cellular development and organismal maturation, but which becomes a rate limiting factor above a certain physical density of the cell colloids. The main statements of the MHA are supported by recent developments in molecular genetics. Specifically, the great majority of the products of oncogenes and antioncogenes are localized to the plasma membrane, indicating a central role of the plasma membrane in mitotic regulation, cell differentiation and senescence.