Lateral mobility of proteins and lipids of cell surface membranes during aging: do the data support 'The Membrane Hypothesis of Aging'?

Many previous studies regarding the change with age in surface membrane fluidity of different cell types, including hepatocytes, as determined by the fluorescence anisotropy method, are in conflict, demonstrating decreased, unchanged or even increased fluidity with age. In contrast, the results of our series of works using the fluorescence recovery after photobleaching (FRAP) technique, which measures protein lateral diffusion coefficients of hepatocyte surface membranes (Dp), have demonstrated that Dp generally declines in a linear fashion with age in hepatocytes of all animal strains and species examined. The major coworker (I. Zs.-Nagy) of these studies insists that our observations support his original hypothesis, 'The Membrane Hypothesis of Aging' (MHA), the primary assumption of which is that changes in cell surface membranes with age cause a general decline in intracellular enzyme activities. However, while it seems clear that cell surface membrane changes do occur with age, a number of past observations including those from the laboratory of this author, provide strong evidence that intracellular enzyme activities do not generally decline with age. This paper presents the data in detail, along with the author's view that the results do not support the main assumption of the MHA, but are more likely related to alterations in membrane functions with age.