Longevity - Unlocking the Secrets of Progeria
By Brad Eitner

Dr. Michael Fossel Ph.D. M.D. professor, Michigan State University, and author of Reversing Human Aging began his research studying the childhood illness progeria. Progeria is a disease that affects the very young. It is a disorder that causes young children to age at an extremely accelerated rate. Most progeria cases die at or near thirteen years old. Strangely, they typically die of the same causes as much older adults ---typically heart disease and cancer. In fact, progeria cases are some of the youngest individuals to die from heart disease.

Progeria is unique genetical condition, in that intellectual function is normal, but there is significant external and internal evidence of premature aging: these children are small, with fragile bones, arthritis, and atherosclerosis. Typically progeric children lose their hair (and what little they have is grey) and their skin is more typical of the very elderly, perhaps 80 or 90 years old. In the process of studying the disease and its causes, two scientific possibilities arose. By comparing the DNA of normal adults with those of progeric children, it was possible to find a location in the DNA that controls aging and how long humans can live. Additionally, any treatments that were effective in slowing, stopping, or reversing aging in progeria cases could probably be used with dramatic effects on normal adults as well.

The DNA itself, and hence aging, seems to be controlled by several things, but perhaps the major single clock that controls our genes lies at the ends of the chromosomes, in our telomeres.

Telomeres are a control-link between chromosomes and DNA. DNA is the most fundamental building block of life. Chromosomes are a much larger component of cells. Telomeres lie at the ends of our chromosomes and any change in their length causes changes in the way our DNA controls our cells. By affecting telomeres, we move more closely to clinical, human therapy, at its most precise, fundamental, and effective level.

It was found--- through research into the causes to premature aging, that, at birth, telomeres in progeria cases were as short as those in normal 80-year old people. It was this that seemed to control aging in the cells of progeric children. This was discovered to be true with normal cells as well. The more times a cell divides, the shorter the telomere, and the less functional capacity the cell has to maintain and repair itself. Over time, the cell therefore becomes defective. Continuation of this process leads inevitably to a biological state called "cell senescence"(complete loss of cellular viability).

Contrastingly, certain cells were analyzed through a series of multiple divisions and they appeared to be "immortal." The telomeres of certain cells did not shorten with progressive divisions. These cells were stem cells, germ cells, and cancer cells.
By analysing what cellular differences appeared between the "immortal" cells (particularly cancer cells) and normal cells in their divisions, the hope was to be able to determine what biochemical factor(s) made a cell resistant to "cell senescence." It appeared after lengthy and intensive research that telomeres did not shorten in cancer and other "immortal" cells upon successive divisions. In the right conditions, some cells will live and even divide/duplicate themselves ad infinitum and never die. This is why cancer is so difficult to stop and cure.

From the study into cancer cells' capacity to maintain telomere length researchers noticed that there were biochemical reasons that induced the "telomeres" in these cells to remain lengthened. By duplicating these cellular life "inducers" they were now able to successfully apply life extension treatment to cells in vitro (in a test tube) and in vivo (in the life form itself).

The research orientation naturally shifted into finding ways to induce telomeres to re-extend in normal cells and see what results came from this type of treatment. Dr. Fossel suggested that this treatment could not only be used to treat age-related diseases, such as arthritis and heart disease, but that it would have the effect of lengthening the healthy lifespan beyond its current limits. Experiments on human skin and vessels are remarkably successful so far.

The next stage of the quest, to aid progeria children, is the most exciting. Cellular death by successive, imperfect-cellular duplication/division is the single biggest cause of aging. In basic terms, a cell needs to divide to preserve the organism it supports, but it must duplicate itself (and maintain its telomeres) perfectly, or else the chance of genetical degradation/mutation increases. This is where most cancer cells originate. A cell often duplicates itself imperfectly---especially late an organism's life.

Cell senescence is caused by a variety of factors, such as a lack of needed crucial biological chemicals (like basic vitamins and minerals), but also of shortening telomeres, which occurs naturally, no matter how healthy our diet or our lifestyle. By inducing telomeres to lengthen, cells were able to duplicate themselves to a "younger condition". This is when Anti-Aging researchers became quite interested in Dr. Fossel's research.

By this time he was a full professor at Michigan State University. He had written many scientific articles and was asked to become the editor-in-chief of The Journal of Anti-Aging Medicine. He has organized The Aging Research Institute, principally to attract private funding for continued research into helping progeria children. I have talked to Dr. Fossel and it is apparent to me that his heart is still close to where it started. His primary focus is to help progeria children. Because of the possibilities for normal adults that have come from his research, Dr. Fossel is quite popular in Anti-Aging circles.
Genetical predisposition to death is the reason why some animals live so much longer than others. If any or all animals lived forever, the world would run out of natural habitat quite profoundly and therefore create immediate extinction. This would not promote a stabilized ecosphere. In fact if all organisms simultaneously mutated to immortality, there would then be the worst worldwide extinction the planet has ever known.

Cell senescence - and aging - appears to be nature's protection mechanism to preserve the over-all ecosphere from "immortal exploiters." Are we at the point where nature and science have become sufficiently acquainted with each other that humans can start to alter the destiny of their own species?

The reason why evolution has been possible up until now is that organisms had a pre-programmed death. This allowed for those organisms that were more genetically promising to have a larger impact of the overall gene pool. Natural selection becomes irrelevant if every organism that is born--- lives forever.

I have now introduced to you just some of the plethora of ethical considerations that Dr. Fossel's research has now created and which he discussed in his first book. Because of the ethical considerations, research possibilities have been put on hold. Dr. Fossel has been writing a new book that is a sequel to his book Reversing Human Aging. In his next book to be published by Oxford Press, he is directing his remarks primarily to the academic community. As the chairman of The Aging Research Institute, Dr. Fossel has been extensively involved with ethical committees organized to review his research and its implications. By the time that the majority of the world's health professionals are as educated on these issues as the readers of the CMA Journal now are, human life-extension trials will have already taken place.

Dr. Fossel and The Aging Research Institute are poised and in the position to proceed with life extension trials on those that are most severely afflicted with aging disorders. The potential of their treatment is significant enough that they have put considerable thought into the "ethical" considerations of "life extension." Dr. Fossel has been busy as the director of The Aging Research Institute to prepare government officials and the academic community for what is the most likely result of application of the research to human beings. His new book will be completed by September.

The full disclosure the upcoming 2003 Life Extension Trials will be reported in two lectures at The Monte Carlo Anti-Aging Conference 6-8 September 2002.

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