Today I'll point out a great open access paper on the evolution of human telomere dynamics: telomere length, how that length changes over time, and especially how it changes with aging. This makes a good companion piece to another paper from last week that covered the differences in telomere dynamics between mice and humans.
This is quite important, since most of the work on this topic involves mouse studies, not human studies. As telomerase gene therapies continue to extend average telomere length and - in mice at least - also extend healthy life span, this is becoming a hot topic in the aging research community.
It is increasingly a good idea to have a grounding of the basics and current scientific thinking on this portion of our biochemistry. Sooner or later someone will be selling telomerase gene therapies to the public as an alleged method to slow the progression of aging, and most likely selling these treatments well in advance of any comprehensive human studies or definitive answers as to their effectiveness. You will find yourself in the position of deciding whether or not to pay the price and undertake the therapies. Better to figure out your position and what would change your mind today rather than later.
Telomeres are repeating sequences of DNA that cap the ends of chromosomes. Their purpose is primarily to act as a part of the limiting mechanisms on cell replication: a little of the length is lost with each cell division, and when they become too short the cell self-destructs or becomes senescent, ceasing replication. For any given tissue the distribution of telomere length among cells is a function of how often new cells with long telomeres are created by stem cells, and how often cells divide.
Stem cells maintain long telomeres through the use of telomerase, which adds more repeating sections to replace those lost to cell division. In humans only stem cells use telomerase, but in mice it has a much more widespread activity. Mice also have much longer telomeres than humans. All of this has everything to do with cancer, of course. The whole complicated arrangement of cells that are limited coupled to a much smaller number of cells that are privileged has evolved because it limits uncontrolled growth sufficiently well for evolutionary success. Without it highly structured and comparatively long-lived species such as our own couldn't exist.
Since stem cell activity declines with aging, it isn't surprising to see that measures of average telomere length also tend to do so - but this is a very poor measure of aging, and really only shows up in statistical studies across populations. There are too many other influences over the most commonly measured types of cell, such as immune cells. So average telomere length, much discussed this past decade, looks a lot like a measure of age-related damage, far removed from root causes.
Given that, why does increased telomerase activity extend life in mice? Most likely for the same reasons that any method of spurring greater stem cell activity improves matters in an old individual: greater tissue repair and maintenance, a net benefit even if it is old and damaged cells that do the work. There are also other, less well explored activities undertaken by telomerase that might be beneficial, such as improvements in mitochondrial function. In mice at least it seems that these benefits come with no greater risk of cancer.
It may be that improved immune function destroys more potential cancers than are created through greater activity in age-damaged cell populations, but that is pure speculation at this point. For humans the effects on cancer risk are much more of a question mark, though it is worth noting that stem cell therapies to date have exhibited far less risk of cancer than was expected at the outset.https://www.fightaging.org/