Caveolin-1 as a prime modulator of aging: a new modality for phenotypic restoration?

Aging can be characterized by structural changes and functional deterioration during the lifetime. for which hundreds of explanations have been put forward. Recently, we have proposed the gate theory of aging. in which gatekeeper molecules at the membrane level would play the prime role in determining the senescent phenotype. Caveolin-1 would be a prime candidate for such a role as a major determinant of the aging process. Caveolin-1 can associate with a variety of molecules, involved in signal transduction, endocytosis and transcytosis, cytoskeletal arrangement, etc. The level of caveolin-1 is strictly regulated to maintain cellular integrity, leading to cellular transformation if depleted, and to the senescent phenotype if overexpressed. In case of senescent cells, the functional and physiological responses to the mitogenic stimuli can be restored and the morphological shape can be resumed by simple adjustment of caveolin-1 status. Therefore, it is suggested that prime modulator molecules, represented by caveolin-1, play a key role in determining the senescent phenotype, either as a physiological response or altered morphology. (C) 2004 Published by Elsevier Ireland Ltd.