The cause of aging as well as the cause of cancer may be due to torsional strain induced in DNA at each division cycle. If this theory is correct, the DNA is separated by pulling apart and twisting each strand of DNA. While the strand is held apart, a new strand is constructed. Then, as the DNA building machinery leaves, the new strands are torqued and the original strands have the torque partly released. Each subsequent cell division results in another increment of torsional strain. Eventually the strain becomes large enough so that transcription fidelity is hampered or even stopped and the cell is degraded or dies. Aging of the organism would be manifested by the appearance and performance of the cell.
The cure for aging and cancer, then, would come from finding the genes producing the cell membrane, and learning how to turn the genes on and off.
A Possible Cause of Cancer and Aging
Most eukaryotic cells age. Each time an aging eukaryotic cell divides, the two daughter cells differ from the parent cell. These differences accumulate as the divisions continue over time. In many cells, the initial differences from one generation to the next are advantageous to the organism – they produce the many different types of cells which give the organism the myriad of different capabilities. The result of some later divisions is deleterious. Eventually the cell ceases functioning and dies. When enough cells die the organism dies.
Some somatic eukaryotic cells do not age. Cells from a cancer patient were used to establish a line in 1952, known as HeLa cells, which has continued hundreds of generations throughout the past 60 years. Cancer cells generally are thought to be immortal.
Another type of cell which does not age is the sex cell. The sex cell from Julius Caesar and his mate produced sex-cells which mated with sex-cells from another couple; the result gave sex cells in a subsequent generation; then to another generation, on to the present day. The descendant sex cell of today’s generation is just as viable as the antecedent sex cell of over two thousand years ago. Thus we think of sex-cells as immortal
From the facts that cells with diploid DNA (of somatic cells which have double strands of DNA) do not age leads to the inescapable conclusion that the unwinding/rebuilding of the interwound DNA strand is the root cause of aging of double stranded DNA cells. Something occurs during the DNA duplicating process in diploid cells that produces aging.
We also know that a wide variety of somatic (i.e., cells with diploid DNA) can escape the aging process. Many types of cell lines become immortal – they become cancerous. The only generally recognized difference in the many different kinds of cancer cells and their parents is that the cancer cell lines do not age. Somatic cell lines which can age and then can be converted to immortal lines strongly suggest that there is something mechanically different between the DNA dividing processes of non-cancerous and cancerous cells.
With this background the author began searching for mechanical differences in the DNA from one generation to the next. First it was speculated that during division of the long string of DNA might get knotted—up in some manner during division. Each subsequent division would somehow produce an additional knot in the daughter strands of DNA. These knots presumably would interfere with transcription producing errors in the transcribing RNA, see Page 186 of Brown . Later research proved that DNA did not behave in this manner. In this knotting theory of aging, the DNA strand was thought of as a flimsy string. Later we realized that DNA is a stiff torsion box.
A major improvement in the understanding of the mechanical properties of DNA is provided by the bookUnderstanding DNA by Chris R. Calladine, et al, . As a result of the information in this book, it became clear what stresses and strains were induced in DNA during separation of the two strands and the construction of the two new strands. Based on this work of Calladine, et al, we determined that at each division, an increment of torsional strain is induced into both pairs of daughter strands. Thus, we had definite proof that the daughter strands of DNA differed from the mother strand. This analysis is presented in Brown .
We do not know how this change of torsional strain from one generation to the next affects differentiation of normal somatic cells. We certainly believe that early cell changes are due to environmental differences but we strongly suspect that the differentiation occurring in the late generations is due to changes in the double stranded DNA. Further, we strongly suspect these changes are not of a chemical nature.
This torsional strain theory of aging is consistent with the fact that germ cells do not age since they are single strands and not interwound. For somatic cells to be consistent with the occurrence of cancer, there must be a mechanism for relieving the torsional strain to produce cancerous cells.
The torsional strain is maintained by one strand of the double helix being wound in one direction while its complementary strand is wound in the opposite direction. Now, the strain cannot be relieved by twisting the double strand somewhere along its length since external torques on the two strands would increase the strain in one strand and decrease that in the other strand.
What mankind would like regarding torsional strain in human DNA follows:
- The initial strain induced at each DNA division coupled with the varying environment for the cell produces the spectacular differentiation which produces eye, bone, nerve, skin etc. cells that make up the human body. The role of strain in these early divisions, if there is any effect, may be useful.
- We know that around the human age of 25 years aging begins to take its toll and we assume the torsion build-up is the cause. We would like to relieve this build-up.
- We further assume that cancer is caused by too great a release of the torsional strain—but only in a few human cells. We would like to increase the torsion build-up in the few cells which are cancerous.
In effect, what we would like is to be able to do is control the amount of torsional strain in most cells of the human body throughout the lifetime of the individual. So doing possibly would cure cancer and aging.
Achieving torsion control is a tall order. World-wide efforts on cancer research and treatment currently are stupendous, and all the work is involved in controlling the proliferation, usually, of just one cell type in a human. However, if our thesis is correct that all cancers (and aging) just involve releasing (and increasing) torsional strain, this understanding might significantly reduce the effort to control cancer. To control cancer the affected cells would have to be identified and killed, which we currently are doing. To cure aging the majority of cells in the body would have to be stress relieved to some extent. We know nature does this with cancer. Thus, discovering the molecules and pathways nature has devised would give the guidelines for curing aging.
Actually, the cause of cancer and the cure for aging may be much easier than it would first appear. Cancer is caused by a mutation in one gene. As a result of this mutation an immortal cell is produced. Since a daughter cell requires proteins produced by many different genes, the one gene cause implies that the mutation produced a modified proton in the nuclear membrane. Such a modification could produce a nuclear membrane which would release the torsion build-up in each segment of DNA extending from one DNA-membrane connection to the next DNA-membrane connection. This release would be for every chromosome in the affected cell. Since between divisions many genes are continually activated there could be a continuous release of the torsion – each time a gene is activated, some of the torsional strain would be relieved.
Incidentally, for some cancerous cells, it has been noted that cancer is more prevalent in cells which are not strongly connected to other cells. This is consistent with the concept that a faulty DNA-nuclear membrane is the root-cause of cancer. The defect in the DNA-nuclear membrane connection would have to permit one of the two DNA strands to rotate in one direction and the other strand in the opposite direction.
To obtain a cure for cancer, our approach has been to kill the affected cell. To cure aging we would have to release the torsion in cells. Nature has a method for releasing the torsion, according to our aging/cancer theory, a controlled amount. For example, a 50 year old patient would need half his cell torsional strain released, and no more. The hope would then be that the patient would return to his/her physiology at age 25.
Ultimately, to cure aging, a drug (or drugs) would have to be developed which would modify the gene(s) that produce the membrane in such a way that the torsional strain would be released by a controlled amount. A further complication is that different cell types in an organism might have different genes involved in producing the nuclear membrane.
Achieving the capability to reverse aging, even if all the above theory is absolutely true, would take a lot of time and a lot of effort. Biological researchers should begin evaluating this theory and proceed as warranted by the results of their investigations.
- Brown, Joseph M., Principles of Science, ISBN 0-9626768-0-2 Basic Research Press, 120 East Main Street, Starkville, MS 39759, 1991.
- Calladine, Chris R., Drew, Horace R., Luise, Ben F., and Travers, Andrew A., Understanding DNA, third edition, ISBN 0-1201589-3. Elsevier Academic Press, NY 2004.
- Brown, Joseph M., The Chemistry and Mechanics of Human Aging, Basic Research Press, Starkville, MS, USA, 2008.