IS OUR DEATH CAUSED BY A CODE?
2nd of the two biggest debates of biomedical world: Are we programmed to die?
DEBATE II: Do we die because we succumb to wear and tear of our biology over the years or due to a DNA code programmed in us before we were born? Longevity has a good explanation for this theory: The wear and tear theory of aging believes that the effects of aging are caused by damage done to cells and body systems over time. Essentially, these systems "wear out" due to use. Once they wear out, they can no longer function correctly. It was first expressed in science by German biologist Dr. August Weismann in 1882. We simply expect that the body, as a mechanical system, is going to break down with use over the years.
A range of things can damage body systems. Exposure to radiation, toxins, and ultraviolet light can damage our genes. The effects of our body's own functioning can also cause damage. When the body metabolizes oxygen, free radicals are produced that can cause damage to cells and tissues. There are some cellular systems that don't replace themselves throughout life, such as the nerve cells of the brain. As these cells are lost, function eventually will be lost. Within cells that continue to divide, the DNA can sustain damage errors can accumulate. Simply the act of dividing again and again shortens the telomeres of the chromosomes, eventually resulting in a senescent cell that can no longer divide. Oxidative damage in cells results in cross-linking of proteins, which prevents them from doing the jobs they are intended to do in the cells. Free radicals inside mitochondria, the powerhouses of our cells, injures their cell membranes so they can't function as well.Not all damage can be repaired fully, and mistakes in repairs may accumulate over time leading to our death.
Programmed aging and death theory is based on aging related slow decline of cellular functions being caused by a epigenetic clock programmed into our DNA. One major development in a Japanese lab of Jun-ichi Hayashi from Tsukuba University may tilt the scales towards this theory. The Tsukuba team has performed some compelling research that has led them to propose that age-associated mitochondrial defects are not controlled by the accumulation of mutations in the mitochondrial DNA but by another form of genetic regulation. The research, published this month in the prestigious journal Nature’s ‘Scientific Reports’, looked at the function of the mitochondria in human fibroblast cell lines derived from young people (ranging in age from a fetus to a 12 year old) and elderly people (ranging in age from 80-97 years old). The researchers compared the mitochondrial respiration and the amount of DNA damage in the mitochondria of the two groups, expecting respiration to be reduced and DNA damage to be increased in the cells from the elderly group. While the elderly group had reduced respiration, in accordance with the current theory, there was, however, no difference in the amount of DNA damage between the elderly and young groups of cells.
This led the researchers to propose that another form of genetic regulation, epigenetic regulation, may be responsible for the age-associated effects seen in the mitochondria. Epigenetic regulation refers to changes, such as the addition of chemical structures or proteins, which alter the physical structure of the DNA, resulting in genes turning on or off. Unlike mutations, these changes do not affect the DNA sequence itself. If this theory is correct, then genetically reprogramming the cells to an embryonic stem cell–like state would remove any epigenetic changes associated with the mitochondrial DNA. In order to test this theory, the researchers reprogrammed human fibroblast cell lines derived from young and elderly people to an embryonic stem cell-like state. These cells were then turned back into fibroblasts and their mitochondrial respiratory function examined. Incredibly, the age-associated defects had been reversed – all of the fibroblasts had respiration rates comparable to those of the fetal fibroblast cell line, irrespective of whether they were derived from young or elderly people. This indicates that the aging process in the mitochondrion is controlled by epigenetic regulation, not by mutations. The researchers then looked for genes that might be controlled epigenetically resulting in these age-associated mitochondrial defects. Two genes that regulate glycine production in mitochondria, CGAT and SHMT2, were found. The researchers showed that by changing the regulation of these genes, they could induce defects or restore mitochondrial function in the fibroblast cell lines. In a compelling finding, the addition of glycine for 10 days to the culture medium of the 97 year old fibroblast cell line restored its respiratory function. This suggests that glycine treatment can reverse the age-associated respiration defects in the elderly human fibroblasts. These findings reveal that, contrary to the mitochondrial theory of aging, epigenetic regulation controls age-associated respiration defects in human fibroblast cell lines. Can epigenetic regulation also control aging in humans? That theory remains to be tested, and if proven, could result in glycine supplements giving our older population a new lease of life.
Similarly David Sinclair's lab at Harvard showed that by upregulating NAD+ in the mitochondria the musculosketal infrastructure of the body rejuvennated to youthful peak levels.
|Harvard's David Sinclair's Formula to Reverse Aging|
The above two have been covered in my earlier post called 'Can we cure aging?' in more detail.
All the three put together provides clear evidence that aging does not create permanent damage or is not caused by wear and tear.
My Conclusion: There is a code that has been planted in the DNA of ALL living things on this planet which is triggered by a epigenetic clock and leads to decline and death of the host. Steve Horvath of UCLA has not recieved the fame and appreciation he deserves for discovering the DNA methylation clock that accurately measures human age. Various strips of DNA has codes that make us grow to adulthood from babies and later, on reproductive maturity, trigger a slow decline leading to death. I don't expect these strips to be in one long chain but in different locations. What is remarkable is zero error rate - we do not see anyone due to DNA mutations cheating death. There are errors which cause various handicaps and deformities but never ever since record of humanity have we observed an error in code regulating aging and death. This shows that Nature gives a lot of importance to death and must have programmed multiple pathways to ensure decline and death in all living things. When we upregulate NAD+ or glycine or AMPK or whatever else has been shown to prolong life in lab animals we are only trying to cure the symptoms. Which can not lead to cure of aging and avoidance of death. There are only two ways it seems that one can aim to achieve this:
1. By disrupting the epigenetic clock by infusion of plasma of a young donor into the patient wanting to reverse aging. The noch protein signals of a donor whose epigenetic clock is signaling body to works at its peak is expected to do the same for the new recipients body as seen in parabiosis models in lab mice pairs. The question is will it do the same in human parabiosis or plasma exchange? Also if it does would the new signals flooding the body in sufficient numbers be able to reset the epigenetic clock of the old human to the age of its young donor or will the benefitial rejuvenation last only up to the life of the signal proteins? If it is the former the parabiosis or plasma exhange would be needed only once every 10 years to reset the epigenetic clock back to the age of 25 (from 35) and if it is the latter then the parabiosis or plasma exchange would need to be done every 4 months.
2. The other way would be identifying which section or sections of the human DNA has the triggers for decline messages to be relayed linked to the progress of the epigenetic clock. DNA does not need to have a message for effecting death. The total body decline ensures that it leads to death. This would be quite a challenge compared to the first option which can be implemented today by any qualified physician using the plasmapheresis machine. Identifying from the 20,000 to 25,000 protein coding genes - it may be a single one that triggers a cascade or it may be multiple ones that work independently or in synergy - too many permutations and combinations to evaluate. It may also be from the huge amount of non coding genes which now are no longer considered junk but also seem to be having some biological function. Needle in a haystack type of situation. But we have already mapped the entire human genome and have invented incredibly powerful gene editing tools like CRISPR - The importance of CRISPR - We are Nature's Robots with a software that dictates everything that happens to us - CRISPR is a tool that allows us to edit this software. We still don't know what to edit but when we do CRISPR will help us execute it.
Once the genes are identified we would need specific binding agents to block it from triggering the functional decline messages. Assuming that the identified genes also do not have other needed functions. Testing which genes play a role in triggering aging decline is very difficult to do as we can not try editing out genes on a living human. So is it impossible to eventually identify the genes triggering aging decline? Of course not. We will achieve this - it is only a matter of time.
|Half a Million DVDs of Data Stored in Gram of DNA|