M.D. West, I. Klimanskaya, R.P. Lanza

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.

Keywords (Optional): 
Stem Cells
Nuclear Transfer