Imortality, stem cells and high dose chemotherapy

Super Interessante, Issue 275, February 2010, on page 46 brings the news that a Cambridge University geneticist Aubrey de Gray, had proposed a period of injecting stem cells to renew the fuel of the human body as one of ways to live more and eventually lead to a long life that could be close to immortality. According to the magazine, the stem cells take on the role of older, damaged by the natural process of cell division that leads to aging, acting as a short period medication that renew the body's organs. A transplant would regular people to be forever young. Further, the magazine Super Interessante says this in a way it's done with stem cell transplants performed to diabetes and multiple sclerosis at the Center for Cell Therapy of USP in Ribeir�o Preto.
However, there are many further details to this story. Gray is a freelance, not part of Cambridge University, but has a PhD from them. Indeed, Gray and colleagues have made a radical proposal in 2004 for the treatment of all types of cancer, consisting of 2 parts. The first would be the elimination of telomerase, the enzyme that is an essential part of cell reproduction. And the second would be these stem cell transplants every 10 years to allow the body to maintain its ability to proliferation of cells, despite the inability of telomerase. Other authors (Ju and Rudolph, 2006) already mentioned that the activity of this enzyme, telomerase, and the ability to generate telomeres are associated with the decline that occurs with age, the ability of the cells have to renew tissues and organs. In most of the various types of stem cells, telomerase activity is low, and telomeres as well, and this feature should be a protection against cancer in this group of cells.

Telomeres are the distal small pieces of chromosomal DNA, composed of TTAGGG sequences. As the chromosomes of these cells will be dividing throughout life, children are becoming the telomeres, the lower its ability to divide and reproduce, until there is widespread death of that group of cells. For example the hair of many men and the ovaries of all women. That is why telomeres are considered a molecular clock. But the more time these cells are alive, the longer will have to be exposed to carcinogens in the environment and food (Aragona and colleagues, 2000). These ideas have not changed significantly over the last decade (Song and Rudolph 2009), except perhaps in the area of cancer, where the concept of genomic instability is well established (Artandi and DePinho, 2010). This instability is the reason for the increased frequency of cancer with age, with progressively lower levels of telomerase activity and smaller physical size of the telomeres. This dysfunction of telomeres leads to two opposite pathophysiological situations, an aging and other degenerative carcinogenesis. The integrity of some check-points of DNA in the cell is to decide which of these two mechanisms predominates.

That's where the radical suggestion of Gray. To delete the genomic instability that allows tremendous versatility of the tumors, they suggested eliminating the possibility of genetic telomere elongation, combined with a stem cell treatment in each decade since the elimination of stretch eliminate the proliferation capacity of tissues.
But a quick search indicates that Aubrey is a very English alternative, the owner of a large beard, son of an artist and an unknown father, who owns an education at the highest levels of the United Kingdom, and a celebrity in the field of rejuvenation. However, not a doctor or have any clinical tradition. Or scientific. It's a celebrity of ideas.

It is unlikely that Aubrey de Gray or his audience, those interested in rejuvenation, understand that the processing of autologous hematopoietic stem cells has much of its effect through the high-dose chemotherapy that the patients are subjected. In particular cyclophosphamide, used in many treatment protocols for immune disorders and cancer, multiple sclerosis to breast cancer, is used in both parts of the transplants autologous hematopoietic stem cells. In the first phase, called mobilization, cyclophosphamide, with or without the help of a growth factor called bone marrow therapy, makes the bone marrow to produce stem cells. In the second phase, another dose, the greater of cyclophosphamide, is part of the treatment that produces a reset of the bone marrow, with the production of large quantities of stem cells. In both phases of many body tissues are the same reset of the bone marrow, and is very likely that they all have a reservoir of stem cells. Thus, there is an exchange of old for new tissue in the gastrointestinal system, urinary tract, the mucosa of the mouth and pharynx, and hair, and falling back stronger, darker color and with greater consistency, even more curly.

The treatment called for pre-stem cell transplantation is a similar phenomenon, but with less intensity than in the transplant, yet clinically apparent to patients and healthcare professionals that they see. It is certainly a very intriguing possibility that the high-dose chemotherapy used for immunological diseases routinely in UNINEURO in Curitiba can have a rejuvenating effect on other tissues in addition to all we see happening. The effect should be even greater with larger doses of Renova or transplantation, using the same line of reasoning. The current medical literature indicates that some limiting factors, such as early menopause and bladder cancer. However, there seems to be an entirely non-travel based on the suggestion of De Gray.

Prof. Dr. Paulo Rog�rio M de Bittencourt, PhD

� Medical Doctor, Federal University of Paran�, 1976

� PhD in Neurology, University of London, 1981

� Registered Specialist in Neurology, Child Neurology, Electroencephalography and Clinical Neurophysiology; Regional Medical Councils of the states of Paran� (CRM-PR 5259) and Santa Catarina (CRM-SC 7499)

� Professor of Neurology, Federal University of Paran�, 1991

� Full Member of the Brazilian Academy of Neurology

� Corresponding Fellow of the American Academy of Neurology

� Member of the European Neurological Society

� Member of the Medical Council of the Brazilian Multiple Sclerosis Society

� Benemerit Citizen of the State of Paran� (2008)

Translated and Adapted by Paulo R. S. de Bittencourt � March 18th