To date progress in the development of stem cell treatments has been accompanied by a markedly lower risk of cancer than was expected at the outset. The charact

To date progress in the development of stem cell treatments has been accompanied by a markedly lower risk of cancer than was expected at the outset. The characteristic decline in stem cell activity with age is believed to be an evolutionary adaptation that reduces cancer risk: there is a balance between on the one hand the risk of cancer due to over-active damaged cells, and on the other hand the failure of tissues and organs due to loss of maintenance activities on the part of stem cells. It is the responsibility of stem cells to deliver supplies of fresh, fit cells as needed to replace those that have become damaged, worn, or have reached the inherent limits imposed on replication of somatic cells. That supply tapers off in old age, however, as stem cells gather damage and spend ever more time quiescent rather than active. Despite the comparative lack of cancer resulting from stem cell therapies, there is still every reason to expect that caution should attend the development of any therapy that spurs greater regeneration in old tissues. The cells in those tissues have a higher load of nuclear DNA damage, and thus a greater cancer risk attends their activity. Yet in practice it isn't working out to be as great a risk as expected, or at least not so far based on the data gathered to date. Why this is the case is an interesting question with no solid answer at this time. The replication limits of somatic cells depend in part on telomere shortening. Telomeres are repeated lengths of DNA at the ends of chromosomes. A little of that length is lost with each cell division, and very short telomeres trigger cellular senescence or programmed cell death. In comparison stem cells retain long telomeres, and thus the ability to continually create new daughter somatic cells with long telomeres to deliver into the tissues they support. This maintenance of telomere length in stem cells is achieved through the activity of telomerase, an enzyme that adds repeated DNA sequences to the ends of chromosomes. Based on all of the above, it is not unreasonable to expect that more telomerase activity in more cells would mean a greater risk of cancer. It would mean cells being more active, and older, more damaged cells being more active. In mice, however, this is not what happens. The risk of cancer actually falls, even as life span is lengthened: researchers believe there is increased stem cell activity and tissue maintenance, but not enough time in even the extended mouse life span for the other shoe to drop and cancer risk to catch up. A firm and comprehensive analysis of what exactly is going on inside these mice is probably still a few years away, however. Nonetheless, the picture painted above suggests that we should be cautious about extrapolating a beneficial balance of time and cellular activity in mice to indicate that telomerase treatments would be similarly great for humans. The span of time is different, our telomere biology is different, and the balance of aging and cell activity is different. On the other hand, the medical community seems to be doing pretty well with stem cell treatments that are just another way of spurring increased cell activity and tissue maintenance in old, damaged tissues. Enhanced telomerase activity seems worthy of further investigation for all the same reasons that stem cell therapies were worthy of clinical development. I don't see telomerase therapies as a treatment for aging per se, however. The approach of increased telomerase activity doesn't address the underlying issues that cause stem cell decline, but instead forces damaged cells to get back to work by overriding the normal reactions of an aged biochemistry. In the view of aging as accumulated cellular damage, stem cell failure with age is an evolved reaction to an increasingly damaged tissue environment. The best way forward is to repair that environment, not override the signals. As first generation stem cell treatments have shown, however, it is possible to achieve beneficial results by taking this path, even while failing to address the root causes of aging. Benefits are good, but we shouldn't let them distract us from the end goal.