Learning to Reverse Aspects of Cell Aging By Observing the Embryo

Adults are old, but children are young: at some point in the early development of an embryo, a collection of presently poorly cataloged processes erase the changes of aging present in the adult cells that created it. It is probably the case that there is little in this that can be applied directly to making us live longer, as the sort of radical restructuring of cells that takes place in the developing embryo would be fatal to the much more complex adult organism. We couldn't apply this to ourselves for all the same reasons that we can't constantly renew ourselves like the tiny creatures called hydra. Our nervous system, mind, and other complex and finely balanced processes depend on the present detailed structure of our long-lived cells, and that structure would be erased.

However, as the authors of this paper point out, there is potentially much to be learned from the embryo that could be of benefit for stem cell treatments. In this case the research community absolutely wants to be able to reverse the damage of aging in induced pluripotent stem cells (IPSCs) generated from an old patient. To a certain extent this already happens, but greater control and effectiveness is desired:

Stem cells are defined not only by their differentiation potential but also by their capacity for unlimited self-replication. The need for prolonged self-replication requires adequate telomere length and telomere maintenance, which can limit the powerful new methods available for generating induced pluripotent cells. IPSCs lacking sufficient telomere length fail to [pass] the most stringent tests of pluripotency, and cannot be maintained in culture over long periods. This might have contributed, in part, to the variable quality of iPSCs during early efforts [and] may ultimately limit the future application of iPSCs in regenerative medicine. To correct this, present efforts in the field of iPSCs have strived to improve the quality of iPSC generated by focusing on telomere dynamics during the process of reprogramming.

Telomeres protect and cap linear chromosome ends, yet these genomic buffers erode over an organism's lifespan. Short telomeres have been associated with many age-related conditions in humans, and genetic mutations resulting in short telomeres in humans manifest as syndromes of precocious aging. In women, telomere length limits a fertilized egg's capacity to develop into a healthy embryo. Thus, telomere length must be reset with each subsequent generation. Although telomerase is purportedly responsible for restoring telomere DNA, recent studies have elucidated the role of alternative telomeres lengthening (ALT) mechanisms in the reprogramming of early embryos and stem cells.

Telomere length in the oocyte is markedly shorter than somatic cells. In contrast, sperm are of the few cell types documented to elongate telomeres over the human lifespan, presumably due to the effects of telomerase activity in spermatogonia throughout the life of the male. Following fertilization and activation of the egg, embryonic cells undergo dramatic telomere lengthening. Notably, telomerase activity remains undetectable in these cells. This effect remains robust in telomerase knock-out mice, suggesting an ALT-dependent mechanism at play in preimplantation mammalian development. Moreover, the lengthening takes place in parthenogenetically activated eggs, which lack sperm input during activation, suggesting that the capacity for telomere length reprogramming resides in the oocyte.

Link: http://dx.doi.org/10.1155/2014/925121


Yes, but perhaps using (future tech) really advanced (programmmable nanobots that are also networked (controlled by), to larger world computer systems), we could go into any cell and, using advanced sensors, manipulators, be able to fix, replace the old cellular parts and make new replacement parts, (edit the dna (remove old code, replace by new code etc) without destroying any important complexes of cells (brain etc)...?

Posted by: gary at April 14th, 2014 4:29 PM

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