Complex organisms are comprised of two fundamental lineages, the germ cell lineage and the somatic lineage. The germ cell lineage produces during each generation the gametes that are required for reproduction, and thus must be immortal. This lineage must undergo meiotic recombination but remains genetically intact, and must retain full replicative potential, reflected, for example, in elongated telomeres and robust mitochondria, so that each new generation begins at the same starting point. A general feature of development of most animals, marking its unique place in the life cycle, is that the germ line forms quite early, often before the major dif-ferentiative milestones of the soma.
The somatic lineage, by contrast, is required to grow and develop in order to form the vessel for carrying the germ line, provide the mechanical means for accomplishing reproduction, and provide some measure of early support to the resulting progeny. The multitude of sizes, morphologies, and behaviors seen among organisms comprise specific adaptations to enable the soma to complete its mission. Once its reproductive mission has been accomplished, the soma becomes evolutionarily expendable, to a degree that varies with the degree of support of the offspring early in their lives. The endurance of the soma is affected by a variety of factors, primarily disease, environmental factors, and the genetically programmed onset of senescence as individuals age.
For most organisms, maximum lifespan is established at birth, being determined by the individual genotype.
For the first time in history, however, Homo sapiens, unique among all other organisms, may possess the potential to modify an individual's maximum lifespan, by manipulating the long-term fate of the somatic component, effectively overcoming the preordained limits imposed by the individual genotype. This potential has arisen out of the new and exciting technology known as mammalian somatic cell nuclear transfer (SCNT), wherein nuclei from somatic cells are transplanted into oocytes, followed by the activation and development of the resulting construct. With this technology, it is now possible, in theory at least, to derive stem cells that are genetically identical to any individual. These stem cells can be manipulated in culture to correct genetic defects, and made to differentiate along specific pathways in order to produce cells for tissue repair.
This exciting new technology has raised a myriad of ethical and moral issues. These will not be addressed here. Instead, this review will address the question: To what degree can stem cells derived by the SCNT method and associated technologies modulate the lifespan of an individual? In addressing this question, three fundamental restrictions of cellular proliferative lifespan will be evaluated, namely, somatic mutation load, mitochondrial fitness, and replicative potential of the genome as reflected in telomere length.
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