by Marvin Ackerman M.D.
When we ask the question headlined in this article we must first clarify what we mean by cells that do not age. We are not talking about single cells that never get old. Rather, we are dealing with cells that are part of a group capable of renewing itself in various ways so that to all intents and purposes the group remains viable throughout the life of the organism. In this age of intensive research into the potential for stem cells to transform themselves into virtually new organs and thereby repair damaged tissues – perhaps eventually permit quadriplegics to walk again, cure genetic diseases, and generally turn the medical world upside down – I feel that we all need a better understanding of the underlying principles involved. An incisive review article called “The aging of lympho-hematopoietic stem cells” by Geiger and Zant, which was published in the April 2002 issue of Nature Immunology (the new journal recently created by the prestigious people who bring us their flagship journal Nature ) delves into the question in considerable detail. It is not my intention to dwell on complex details of this sort, but rather to extract those fine factual and theoretical facets inherently contained in a treatise of this magnitude.
The principles involved in this discussion are certainly not new. As far back as 1972 Harrison, writing in Nature New Biology, noted that cells which were destined to become red blood cells in mice could be transplanted outside the mice and then were capable of living 21 months past the life span of the mice from which they came. Eventually it became apparent that stem cells destined to produce red blood cells, or hematopoietic stem cells, have the capacity to continually renew themselves. This implied that these cells do not age and that the reason for this is to provide animals with an “undiminished replenishment of blood cells throughout the lifespan of an organism.” However, opponents of this concept believe that these cells actually do show the signs of aging and that their life spans are decidedly limited. These authors favor the view that “age-related functional decline in adult tissue hematopoietic stem cells limits longevity in mammals.” Like other long-lived cells of the body, which comprise a major portion of our organs, replacement is infrequent. So they gradually change their functional abilities leading to what we call aging. To keep doing their job, they must reproduce or at the least, self-renew. Study of these phenomena has been rather limited because older mice are relatively hard to acquire. Researchers had to purchase them when they were young and then wait until they got old enough to proceed.
Research was nevertheless done, and it became apparent that hematopoietic stem cells do appear to replenish themselves. The older the animal the more there are of these cells. On the other hand, a greater number of older cells are needed to reconstitute the bone marrow than younger cells. In truth, studies showed that the older cells are “at a significant disadvantage relative to their young counterparts.” It was even possible to demonstrate defects in the older cells. Furthermore, the farther back they went the more capable were the cells so that fetal cells had a competitive repopulation advantage over young adult cells. The conclusion from these and other studies suggested that this decrease in potential depends upon age and starts right at the beginning, during fetal life. Another factor playing a major role is genetic regulation because different strains of mice had different abilities with regard to maintaining the cell populations, but findings during these studies tended to negate any role played by immune factors. The role played by age seems to involve a quieting of activity rather than gradual loss of numbers of cells or individual aging of cells. The fact that senescence may not be involved can be detrimental in certain situations wherein the strategy is to limit a cell’s likelihood of becoming cancerous from cumulative cellular damage and genomic instability. Another factor that seems to be little involved in the changes of aging is the surrounding tissues. The changes appear to be basically inherent in the cells themselves, not in their stroma.
In spite of the difficulties involved in obtaining appropriate animals for investigation, evidence gleaned from a good number of studies over the years points to the conclusion that hematopoietic stem cells can and do maintain normal blood cell counts for a lifetime, but as the aging process takes over this capability is diminished. When crises arise, they fail to have the functional reserves needed to meet the challenge by producing large numbers of progeny. Aging, however, does not tend to decrease the numbers of these cells, which may actually increase. It’s literally a case of the effect of quality superseding that of quantity. Future research should focus on the molecular characteristics of these stem cells. Stem cells from other tissues may not be much different in this respect than those of the red blood cells. Once we have a more widespread picture of how the quality of stem cells varies in other tissues we may obtain a better idea as to what are the determinants of longevity.
Personally I don’t think that I am destined to benefit from these investigations into the ability to prolong life. To those readers and your own progeny who are still young enough to reap those benefits I salute you. I want you to know that I just knocked on wood in the hope that the world that you will inherit in which to pass those bonus years will prove to be a good deal better than the one to which we seem to be heading.
The ancients preserved their kings and queens,
Wrapped them in cloth and embalming fluids,
Built them immense pyramids in which to dwell,
And surrounded them with their worldly goods.But once you’re dead it’s all for naught,
Be you underground, or in a jar on a shelf,
So dream your dream of immortality now,
But remember you’re merely deluding yourself.
