Senescence and immortality

The body of any mammal consists of an interacting collection of cell populations. These cell populations are distinguished not merely by the different types of specialised cell they contain(blood cells, liver cells, nerve cells, etc), but by the general model used by each population to maintain a steady-state. in this context, Michalowski identified two population types: Hierarchical, or H-type populations, and Flexible, or F-type populations.

There are two key properties which can be used to characterise cell populations: proliferation and differentiation. If the cells in a population are dividing (via the cellular process of mitosis), and thereby reproducing, then they are said to be proliferating. If the cells in a population are highly specialised in the function they perform, then they are said to be differentiated. Not all cells in the body of a mammal are dividing, and not all the cells in such a body are differentiated.

An H-type population contains three sub-populations: stem cells; maturing partially differentiated cells; and mature, functional cells. Stem cells are non-differentiated cells, which, when they undergo mitosis, are capable of both renewing their own numbers, and producing the progenitors of the more specialised cells in the population. Stem cells have infinite proliferative capacity by virtue of an enzyme called telomerase. In the absence of this enzyme, cells can only undergo a finite number of divisions before the telomeres on the ends of their chromosomes become excessively shortened. The maturing, partially differentiated cells are the descendants of the stem cells. These cells undergo successive divisions, and become increasingly differentiated as they do so. The mature, functional cells, are the descendants of the partially differentiated cells. The mature cells are fully differentiated, but incapable of further division. Given that the other cells in the hierarchy are dividing and multiplying, the mature cells must have a finite lifetime to maintain a steady-state in the organ or tissue. The classic examples of H-type cell populations are the hematopoietic bone marrow, the intestinal epithelium, and the epidermis.

Michalowski defined an F-type population as the opposite extreme, a population with no stem cells, in which all the cells are differentiated, and the differentiated cells are capable of undergoing further mitosis. To maintain a steady-state, the cells in such a population rarely divide, but are capable of doing so in the event of damage to the tissue or organ. The liver is often quoted as an example of such a cell population.

Michalowski also acknowledged that there is a spectrum of H-F hybrids between the two extremes, populations which both contain stem cells, and differentiated cells capable of further division. In fact, I wonder if organs such as the liver are actually H-F hybrids. The problem I have with Michalowski's F-type is that the cells are defined to possess an infinite proliferative capacity. This is only possible with telomerase, yet as I understand it, the only cells which utilise telomerase are stem cells and cancer cells. Perhaps, then, an F-type population is merely a limit to which various organs and tissues can approach.

What is interesting here is that the mammalian body possesses at least two different solutions to the problem of maintaining a population of cells in a steady-state. An H-type population is potentially immortal, (given a supply of energy for an infinite time). In contrast, in the absence of telomerase, an F-type population will evolve towards senescence after a finite time.

It's also interesting to note that, whilst mammals have evolved over millions of years by means of reproductive populations, the individual bodies which are the upshot of that evolutionary process, utilise various types of reproductive sub-population, not to evolve, but to maintain a steady-state.