Wow C David!
That’s an awful lot of good data you provide us. Of course that’s your field of expertise – but it definitely rules out telomere length as a function of cell divisions alone. Endurance training (reminds me to go the the gym today) up-regulated telomerase and endurance-trained older adults have longer telomeres on the leukocyte chromosomes. So endurance training seems to me more likely to cause the production of new blood cells from hematopoietic progenitor cells (a few thousand in people) – and that should accelerate telomere attrition? And yet telomeres are longer. That endurance-trained older adults have longer telomeres could be explained by say the elimination of short-telomere-ed cells through rough usage. But the induction of telomerase in the heart with endurance training explains that it is the addition onto extant telomeres that is the cause – probably. So where in the heart was telomerase expressed (and how did they know)? In the cardiac stem cells self-renewing? (That would be nice.) The fact that leukocyte telomere length is preserved in endurance trained adults is both encouraging and discouraging ; encouraging, because we, with our own efforts, can affect our lifespan length, and discouraging because endurance-trained adults do not live appreciably (in terms of multiples of the normal lifespan (as in C. elegans – where we can produce a ten-times normal lifespan by mutations to nutrient receptors and sensors)), longer. I think the telomere length is more important in keeping certain populations of cycling cells at certain levels – tissue homeostasis, but it clearly is responsible for some diseases of aging as numbers of cells reach replicative senescence send signals throughout the body and convert to senescent cells and increase the body’s inflammation. Or they die (apoptose – is that a verb?) and so lead to cytopenia. So I don’t think telomere attrition is the cause of aging – again there exists a remedy for it (telomerase) and the fact that it’s not used can have two explanations: 1) that it cannot be used, because say a mutation has eliminated the telomerase TERT gene, or 2) that it is simply not called upon after what would normally be self-renewal to keep the telomeres long. The likelihood that the TERT genes are randomly knocked out by mutations (while most other genes are not) – or made inaccessible by epigenetic mutations – again while other genes are not- in all stem cell populations at particular adult lifestages – is about as likely as tossing a quarter and having land on its edge. So explanation 2) is the correct one – the cell has functional telomerase but doesn’t use it. Why not – did it ever – in young bodies, when stem cells self-renew, do they use telomerase to maintain their telomere lengths? I believe they do, but eventually do not in aging. If that is the case why do they stop? My own thinking leads me to the conclusion that they are either ordered not to, or lose their orders to do so. In either case I think their environments determine this. I believe this is non-cell autonomous.