• caveolin;
  • aging;
  • gatekeeper;
  • restore;
  • replace

Abstract: It is generally accepted that aging is a phenomenon of irreversibility, inevitability, and universality with parenchymal loss and functional decline. Consequently, the major goals of aging research are focused on the development of a replace strategy of the aged organs or cells, based on immortalizing tools, stem cells, or artificial substitutes. Recently, however, a new concept of functional recovery has been introduced on the basis of the functional restoration of the responsiveness of the senescent cells toward a variety of agonists, including growth factors. The aging phenotypes of hyporesponsiveness and morphological alteration are shown to be readily adjusted by modulation of the several membrane-associated molecules, named gatekeeper molecules, among which caveolin is one of the major determinants. Caveolin is the essential component of the caveolae, responsible for regulation of signal transduction, endocytosis and trancytosis, and cytoskeletal arrangement via its scaffolding domain. The caveolin status is associated strictly with cellular transformation, if depleted, and with senescent phenotype, if overexpressed. Therefore, simple reduction of caveolin status in senescent cells leads to restoration of the functional responsiveness to mitogenic stimuli and even of the cellular shape. These data strongly suggest that the gatekeeper molecules, represented by caveolin, may play the prime role in determination of the senescent phenotypes. From these results, it can be summarized that the replace principle would not necessarily be the essential one, but the restore principle can be somehow substituted for the betterment of the aged cells and organisms.