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Telomeres are repeating sequences of nucleic acids that cap the ends of chromosomes in the cell nucleus and stop actual gene-coding DNA from being chopped off w
by reasonattlm 11y ago
Telomeres are repeating sequences of nucleic acids that cap the ends of chromosomes in the cell nucleus and stop actual gene-coding DNA from being chopped off when a cell divides. The mechanisms of DNA replication require extra leg room at the ends of the strand, a trailing sequence that is not copied over to the new strand under assembly - and the primary role of telomeres is to be the part that is dropped on the floor. A little of their length is thus lost with every cell division. This shortening acts as a clock to count cell divisions, and cells with very short telomeres stop replicating - they either enter cellular senescence (which ideally then causes the immune system to destroy them) or destroy themselves directly via programmed cell death mechanisms.
Telomere length is more dynamic than this simple picture, however. In some cell populations, such as the various types of stem cell that maintain tissues and produce new cells to replace those lost or damaged, an enzyme called telomerase continually lengthens telomeres so as to allow a cell lineage to continue dividing indefinitely.
Ordinary, non-stem cell populations exhibit a range of telomere lengths, some short, some long. You might imagine that a population of cells replenished more frequently or recently by stem cells will have longer telomeres on average. A population that is receiving less support might have shorter telomeres. Researchers have shown that a higher proportion of short telomeres in white blood cells correlates well with ill health or stress, and somewhat correlates with age. Some more complex measures of telomere length, a step above just taking the average, have been shown to correlate well with age, however, and other techniques do a fair job of predicting future life expectancy in laboratory animals.
A few years back a brace of startup biotech companies were aiming to address aspects of aging by lengthening telomeres through the use of telomerase. None of that went anywhere, unfortunately, but it's possible that they were just too early - it is frequently the case that all of the first batch of companies in a new area of biotechnology fail. It's a tough business to be in. I was a skeptic at the time regarding their potential for success based on my expectation that telomere length will prove not to be a root cause of aging. It looks a lot more like a marker for (a consequence of) some of the responses to the root causes of aging, in particular the reduction in stem cell activity that is characteristic of old age.
Nonetheless, researchers are demonstrating extension of life in mice through telomerase these days, but it is as yet unknown as to exactly why this works. Perhaps it makes stem cells work harder to maintain tissues, perhaps there is just one critically limiting type of stem cell or tissue that benefits from more telomerase, or perhaps it involves other effects causes by increased levels of telomerase that have nothing to do with telomere length. It is worth bearing in mind that there are considerable differences in natural levels of telomerase and the resulting telomere dynamics between mice and people, however. Telomerase therapy is probably not something you'd want to just up and try without the research community first obtaining a much greater understanding of why it works to extend life in mice.
Why? Well, the risk of telomere lengthening in humans is cancer. Any mechanism that globally, or possibly even narrowly, extends telomere length in people will raise the risk of suffering cancer. The whole system of telomere dynamics and cellular senescence is intimately tied to the processes of cancer suppression, while all cancers evolve ways of lengthening their telomeres to allow unlimited cell division. Boosting your telomerase levels looks a lot more risky to me than, say, undergoing first generation stem cell transplants.
There continues to be a lot of activity in telomere research and development. The present brace of telomere-related biotech startups are commercializing ways to measure telomere length rather than extend it. The products are tests that will at first add another measure to inform patients on the state of their health, then possibly act as an effective biomarker of biological age, and perhaps later prove useful in further research if it turns out that telomerase-based therapies can be beneficial in humans.