Fine-Tuning Regeneration for Longevity

The evolved balance between cancer resistance and tissue maintenance is an important determinant of longevity - but it can be fine-tuned so as to have your cake and eat it, as researchers have found in recent years. Here is another example, in flies this time: "Somatic stem cells are critical for regeneration of many tissues, thus ensuring long-term maintenance of tissue function. Proliferation of stem and progenitor cells has to be limited, however, to prevent hyperproliferative diseases and cancer in aging animals. This conflict between the need for stem cell proliferative potential and cancer prevention compromises regeneration in many high-turnover tissues of aging animals, including humans. ... In old flies, intestinal stem cells (ISCs) hyperproliferate, causing an accumulation of mis-differentiated daughter cells (a phenotype termed intestinal dysplasia). We show that the balance between regeneration and dysplasia in this tissue significantly influences lifespan. When ISC proliferation rates are reduced, but not completely inhibited, dysplasia is limited and lifespan is increased. This can be achieved by moderately reducing insulin and stress signaling activities, as well as by expressing protective proteins in somatic stem cell lineages. Our results show that optimizing proliferative homeostasis (i.e. limiting dysplasia, but allowing sufficient regeneration) in high-turnover tissues is an efficient strategy to extend lifespan." The more that is known about the fine details of metabolic and cellular processes, the more that might be done to tinker with them to extend life. But this will never be as efficient a path forward as repair technologies - when we strive to identify and repair damage within our biochemistry, we have no need to fully understand every aspect. We know what a young metabolism and cell look like, and we are trying to revert the clearly identified differences between young and old.

Link: http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1001159

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