Strategies for the Reversal of the Aging of Human Somatic Cells
M.D. West, I. Klimanskaya, R.P. Lanza
Advanced Cell Technology, Inc., 381 Plantation St., Worcester, MA 01605, USA
An increasing number of the manifestations of aging are being
attributed to telomere shortening and/or damage. Nuclear transfer
offers the possibility of transiently reactivating telomerase activity,
restoring germ-line telomere length, exchanging the somatic cell
mitochondria with that of the oocyte, and reprogramming the chromatin
of somatic cells to an embryonic pattern of gene expression. The
resulting embryonic stem cells could theoretically be differentiated
into a wide-array of somatic cell types useful in the treatment of a
number of age-related degenerative diseases, and if aging in the donor
somatic cells has in a broad sense been reversed, the applications in
interventive gerontology could be profound. We are exploring two
strategies to reprogram human somatic cells; namely, nuclear transfer
and "fusion" strategies. Nuclear transfer using human oocytes or
alternative suitable recipent ooplasts provides the advantage that
evidence of complete reprogramming in animal models is evident where
the resulting preimplantation embryos are transferred to a uterus to
generate live births. "Fusion" strategies, wherein the somatic cell is
permeabilized and exposed to undifferentiated cell extracts or wherein
the somatic cell nucleus is transferred to an undifferentiated cell
cytoplast offer the advantage of reprogramming somatic cells without
the use of oocytes or embryo production, factors that have slowed the
widespread use of the technology. However, in contrast to nuclear
transfer, there is as yet no whole animal data as is the case in
nuclear transfer, to assess the extent of reprogramming or the
normality of the resulting cells. Progress in reprogramming human
somatic cells by these reprogramming strategies, assessing the extent
of the reversal of markers of aging, and testing the use of the cells
in animal models of age-related disease will be presented.
Key words:
Stem Cells, Telomeres, Telomerase, Nuclear Transfer, Mitochondria
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