While there have been many hypotheses on the causes of aging, the precise mechanism of cellular aging, and how it can be measured, remains unclear.
A study in 2016 (1) has illuminated the differences between various measurements and possible mechanisms of cellular senescence and aging.
One widely-reported association between telomere length and aging has been proven to be inconsistent. Over-expression of oncogene, and DNA damage, have also been seen as contributing to cellular aging. But the oncogene-induced senescence is really a tumor-suppressive mechanism. Oncogenes, which cause abnormal DNA replication, as well as short telomere length, are both detected by cellular mechanisms as damaged DNA and then initiate senescence of the cell.
Another change related to aging is the level of methylation at some CpG sites. This has been developed by the authors as a tool for estimating chronological age. The study shows that this “epigenetic clock” measurement is much more accurate in measuring chronological age than telomere length, and correlates well with physical factors in the elderly.
The conclusion of this study is that epigenetic and chronological cellular aging, as measured by CpG methylation, are independent of cellular senescence caused by telomere length or DNA damage. The results of this and other studies show that even if telomere length is artificially maintained by telomerase, the cell continues to age. The telomeres act as a mechanism for restricting the number of cellular divisions, not for preventing aging. Cellular senescence, due to DNA damage, telomere shortening, oncogenes, or whatever, is merely a mechanism for removing cells that are seen as damaged, while the rest of the cells continue to age naturally. Cellular aging “is an intrinsic mechanism that exists from the birth of the cell and continues” throughout its life.
Which brings us to the larger questions of what causes cellular aging. Do the methylation markers cause aging, or does aging from another source cause the methylation? It is known that methylation is a mechanism for turning certain genes on or off. Since each species has a specific life span, it is clear (at least to me), that each species has evolved a genetic mechanism for aging and death at a precise moment. Methylation may be a mechanism for directing the cell to begin aging.
One hypothesis for the specific rate of aging of each species is that each species, in order to adapt to the rate of change of the environment in the niche it inhabits, developed at optimal time of reproduction. If the environment (food and water supply, weather, temperature, predators, etc.) changes quickly, the organism must adapt to reproduce quickly. It evolves a rapid rate of development to quickly reach sexual maturity and produce offspring with mutations better able to withstand the changes in the environment. Once reproductive maturity is reached, evolution can no longer exert an influence to keep the parent organism alive. In fact, there may even be evolutionary pressure for the parents to die off quickly in order to minimize competition with the offspring and thus increase their survival rate.
It is unclear to me, then, why so much money is currently being spent on researching what appear to be the consequences of aging rather than focusing on the genetic process itself. DNA is a code, a very complicated code, but a code, nonetheless. Why not focus on breaking this code, and finding the obviously predetermined genetic cellular aging mechanisms and limits on lifespan that each species has evolved?
We age and die because evolution could not function otherwise. But now we have reached a stage in our development where we no longer have to rely on natural evolution. Soon, hopefully, we will understand our genome to the extent that we will be able to control how we develop (and age). We will no longer be an evolving species, but a self-creating one. Of course, once we reach a stage where we no longer age, other problems will arise (reproductive, social, economic, political, psychological, etc.), as I have discussed in previous posts.