The author noted here sees aging as programmed, in the sense that it is an epigenetic program selected for by evolution because shorter life spans prevent population-level ecological issues. His writing is usually a good illustration of how this concept of aging as a selected epigenetic program leads to very different conclusions on the nature of aging as a whole, as well as on any specific research result. In the case of this post, the topic is the role of telomere length and telomerase in aging, and their relationship to the established DNA methylation biomarkers of aging.
The mainstream view of epigenetic change with age is that it is a reaction to accumulated cell and tissue damage, one that evolved in the limited selection pressure thought to characterize post-reproductive life span. Both damage and epigenetic changes are components of a decline that is an accidental outcome of the aggressive selection for success in early life. Evolution produces biological systems that do well initially, then corrode and fail in a haphazard fashion, because there was no selection for long-term function. Thus systems that generate damage as a side-effect of normal operation, and systems that have limited capacity that fills up and causes issues in later life are found everywhere in our biology.
The debate over programmed versus non-programmed aging, and the ordering of cause and effect between cell and tissue damage versus epigenetic change, will be settled over the next decade or two. If one side produces therapies that revert epigenetic changes and the other side produces therapies that repair cell and tissue damage, then simple observation of the results will determine who is right. The greatest extension of life span and health will point the way to the correct interpretation of the process of aging.
Just a few weeks ago, I learned of a new study linking telomerase to the changes in DNA methylation that the epigenetic clock associates with aging. The implication is that telomerase accelerates aging. It began with an investigation asking what genetic variations are associated with people who age faster or slower than average, according to the epigenetic clock? Researchers performed a genome-wide search for statistical correlates and the standout association was telomerase. People who have small genetic variations that support greater telomerase expression tend to have longer telomeres, but they also tend to age faster, as measured by the epigenetic clock.
The association between telomerase and accelerated aging (measured by methylation) was found in the genetic statistics, and then confirmed in a cell culture. When telomerase was artificially activated in the cell culture, the methylation patterns changed in the cells consistent with older age according to the epigenetic clock. In fact (and remarkably in my opinion) they found no epigenetic aging at all in the cell cultures that lacked telomerase. Could it be that telomerase is the one and only driver of epigenetic aging at the cellular level?
So, what's going on? My inclination is always to think in evolutionary terms. Fixed lifespan, (especially when modified conditions of food stress) is helpful in preventing population overshoot that can lead to famines, epidemics, and extinction. But whenever a trait is good for the community and bad for the individual, there is a temptation for the individual to cheat. In this case, cheating would mean evolving a longer lifespan via selfish genes, such as those enabling greater telomerase expression, that spread rapidly through the population. Individual competition would erase aging if left unchecked. The results would be great for individual fitness, but soon would be disastrous for the population. Thus evolution places barriers in the way of individual selection for ever longer lifespan.
My guess is that the connection between telomerase and epigenetic aging is an example of antagonistic pleiotropy crafted by natural selection in its long-term mode. Limiting lifespan has been so important to the viability of the population that evolution has arranged to protect it from leaking away due to cheating, and antagonistic pleiotropy is one of the ways in which this is arranged. I believe that the preponderance of evidence still indicates that activating telomerase has a net benefit for lifespan, but that probably we can add at most a few years by this route. I think that epigenetics is much closer to the core, the origin of aging, and that interventions to modify epigenetic aging will eventually be our holy grail.