S.C. Park

It is generally accepted and even believed that aging is a phenomenon of irreversibility, inevitability and universality with parenchymal loss and functional decline. Consequently, the major goals of the aging researches are focused on the development of the replacement strategy of the aged organs or cells, based on immortalizing tools, stem cells or artificial substitutes. But recently, 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 the hyporesponsiveness and morphological changes are shown to be readily adjusted by the several membrane-associated molecules, named gate-keeper 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 transcytosis, and cytoskeletal arrangement via its scaffolding domain. The caveolin status is strictly associated with cellular transformation, if depleted, and senescent phenotype, if overexpressed. Therefore the simple reduction of the caveolin status of the 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 roles in the senescent phenotypes. From these results, it can be summarized that replacement theraphy would not necessarily be the essentiall, but restoration policy can be somehow substituted for the betterment of the aged cells and organisms, suggesting the value of the dichotomic approach of aging research in contrast to the deterministic approach.

Keywords (Optional): 
gate keeper