Functional Efficiency of the Senescent Cells: Replace or Restore ?
S.C. Park
Aging and Apoptosis Research Center, Seoul National University, 28 Yon Gon Dong, Chong No Gu, Seoul 110-799, S. Korea
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.
Key words:
caveolin, aging, gate keeper, restore, replace
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