Aging (Modified SENSF's Theory)

[NathanielZhu]

AGING

If anyone has read Ending Aging by Aubrey de Grey, you'll immediately see that he takes a sort of engineering perspective to stopping aging which I agree is a much better than "messing with the complex genetic pathways of our body" but I've taken his idea is little further by trying to further remove what I don't think is a necessary practice.

 

Please tell me what you think about my summary of my hypothesis.

 

 

"We age because homeostasis is lost. There is an abnormal balance of chemicals which leads to an abnormal expression of genes. That is obvious. What is less obvious is what causes many of these disorders. I’ve determined that many of the seemingly undestructable diseases are actually the result of damage to something else.

 

The SENS Foundation has outlined 7 forms of damage: Intracellular junk, Extracellular Junk, Tissue Stiffening, Cell loss, mutant mitochondria, zombie cells, and nuclear mutations.

 

I think however the problem of nuclear mutations isn’t a concern and that includes cancer assuming all other problems are repaired and this includes mitocondrial mutations. Solution to aging: Repair the Junks and Loss of cells.

 

The main reason why I think mitochondrial mutations is not a big concern in the near future is because is mitochondrial aging in different organisms. The mitochondria of rats are similar to the mitohcondria of humans and yet the mitochondria of rats age a lot quicker. By the end of a rat’s lifespan, the mitochondria has degraded to a shell of its youthful self in only 13 months. Evolutionary biology has ruled that evolution doesn’t purposely reduce an organism’s lifepsan so that fact that human and rat mitochondria have such different vitality periods means that the problem lies elsewhere. Perhaps something that is causing the mitochondria to run with less efficency in rats than in humans.

The same concept applies to Nuclear mutations but more specifically cancer. Cancer cells often comes about in both young and aged animals but why doesn’t the young animals get cancer as frequently as aged animals? It’s because it is destroyed! By what? The immune system so that’s the problem. We know immune system function is reduced tremendously in aged people than in young people and we also know that the DNA In young people can’t possibly be any “less damged” than old people because the DNA of young people come from old people so we can only assume that their DNA has similar damage – albeit the damaged is a lot less due to protection from it’s surrounding cells but that doesn’t matter because millions of years would eventually accumulate the damage until the information is no longer viable to product the next generation of offpring but that obviously isn’t the case because the next generation is just as vital as the previous generation in most cases and that is because SOMETHING ELSE is missing: the actual problem.

 

Also consider how the next generation offspring get their mitochondria. They get it from their older and more damged parents. If the damage were to be transferred down the line generation to generation then eventually the mitochondria would be so degraded as to not product any ATP and thus the line would end but it doesn’t happen that way. The next generation of newer mitochodnria is healthier than the older mitochondria from the previous generation of mitochondria because SOMETHING IS MISSING: the damage of aging.

Here’s the obvious part: egg and sperm joins to form a fertalized egg that then divides into the next generation. If the DNA was the cause of the problem than these clunky damaged DNA from the previous generation would cause the next generation to be unhealthy but that isn’t the casue because the actual cause of aging is missing or very dilute and that is exactly what happens. The junks of aging are diluted after each sucessive division of the cell so that after the billionth of so division of the cell there is basically no damage at all and the offspring appears young.

 

Therefore, the solution to aging is to get rid of the build up of junks and that includes only the Intracellular junk, extracellular junk, junk that causes tissue stiffening, and cellular junk (indestructable cells) in addition to replacing missing cells."

Edited January 9, 2013 by NathanielZhu

[CharonY]

We age because homeostasis is lost. There is an abnormal balance of chemicals which leads to an abnormal expression of genes. That is obvious. What is less obvious is what causes many of these disorders. I’ve determined that many of the seemingly undestructable diseases are actually the result of damage to something else.

 

I have issues with that. It assumes there is some kind of homeostasis within our body and/or cells. However, aging is progressive (think of cell maturation, for example). There is no phase that I could think of where there is a homeostatic condition resulting in "normal gene expression" (I also have no clue what that is) and hence, no aging (for a while, at least). This simply does not agree what we know about cell development and aging, for example (i.e. progressive mitochondrial damage; telomere length and telomerase activity, etc.).

With an erroneous premise, further deliberations are not likely to be accurate.

Edited January 10, 2013 by CharonY

[NathanielZhu]

 

I have issues with that. It assumes there is some kind of homeostasis within our body and/or cells. However, aging is progressive (think of cell maturation, for example). There is no phase that I could think of where there is a homeostatic condition resulting in "normal gene expression" (I also have no clue what that is) and hence, no aging (for a while, at least). This simply does not agree what we know about cell development and aging, for example (i.e. progressive mitochondrial damage; telomere length and telomerase activity, etc.).

With an erroneous premise, further deliberations are not likely to be accurate.

 

Yes aging is progressive and so is cell maturation but it is now generally accepted among aging researchers that development (maturation) is different from aging. People see see aging in the way a 5 year old looks physically different than a 15 year old but that is due to development (maturation) which is a highly controlled process and aging happens simultaneously however the effects of aging isn't seen until after development (maturaton) which is also when evolution no longer creates any ways to combat the inefficencies of metabolism. For example, the build up of plaques is an aspect of aging but it is independent is cell maturation. A 10 year old is still in the process of maturation and even though the negative effects of aging has reached a noticeable threshold, that doesn't mean it isn't happening.

 

No such thing as homeostatic conditions? C'mon. If you suddenly drink 20 gallons of water you'd die. Obviously homeostasis is disrupted, It's true there's no set condition for homeostasis but each organism has it's range of conditions if you will where it will be healthy. A plugged up artery is not a characteristic of homeostasis so perhaps our dispute is in word choice.

 

Telomerase activity is involved with stem cells/tissue repair and I haven't written about that yet but basically, with the reduction of the stem cell pool, therapies will be needed to replenish that and that would replenish the telomeres of those new stem cells but fr the most part it seems that evolution used telomere controlled senescence as a means of prevent diseases like cancer that results from cells that build up to much damage (genetic/nongenetic).

[jp255]

Your initial post contains a few factual errors, and some support for some of the claims you make would have been useful.

 

 

 

The main reason why I think mitochondrial mutations is not a big concern in the near future is because is mitochondrial aging in different organisms. The mitochondria of rats are similar to the mitohcondria of humans and yet the mitochondria of rats age a lot quicker. By the end of a rat’s lifespan, the mitochondria has degraded to a shell of its youthful self in only 13 months. Evolutionary biology has ruled that evolution doesn’t purposely reduce an organism’s lifepsan so that fact that human and rat mitochondria have such different vitality periods means that the problem lies elsewhere.

 

The involvement of the mitochondria in the process of aging is a concern. Decline of function, accumalation of mutation and increased Reactive oxygen species (which damage DNA, proteins and lipids) are examples of reported changes as individuals age. There are a number of papers on this topic. http://www.ncbi.nlm.nih.gov/pubmed/22399429 by Lee HC and Wei YH (2012). I couldn't find a free article in my quick search. The point is clear though.

 

I disagree with your comment you make "the problem lies elsewhere". It seems to me that there are various problems which all contribute to aging, as opposed to one culprit as your wording suggests.

 

 

 

Cancer cells often comes about in both young and aged animals but why doesn’t the young animals get cancer as frequently as aged animals? It’s because it is destroyed! By what? The immune system so that’s the problem. We know immune system function is reduced tremendously in aged people than in young people and we also know that the DNA In young people can’t possibly be any “less damged” than old people because the DNA of young people come from old people so we can only assume that their DNA has similar damage – albeit the damaged is a lot less due to protection from it’s surrounding cells but that doesn’t matter because millions of years would eventually accumulate the damage until the information is no longer viable to product the next generation of offpring but that obviously isn’t the case because the next generation is just as vital as the previous generation in most cases and that is because SOMETHING ELSE is missing: the actual problem.

This paragraph about cancer is incorrect and is contraditory. You state that young peoples' DNA isn't any less damaged then say the damage is probably alot less due to protection from surrounding cells. The paragraph itself doesn't read well, think more on the subject before posting and read up on the subject. I'm just going to give you a very simple explanation, you can read up on it yourself in more detail.

 

Individuals accumulate mutations over time, some mutations contribute to the development of cancer and others don't, so the risk of cancer rises with age. An individual has trillions of cells which can all accumulate mutations, there is a risk that any one of these cells can become cancer. Whilst there are a very large amount of accumulated mutations in total amongst all of the cells, each cell will have a far lower number. Only one germline cell will go on to form the offspring, and any mutations it has will be present in all cells, so the offspring inherits only a small number of mutations from the parent.

 

Dumbed down explanation but I think you didn't consider that somatic mutations are not heritable across generations, that all acquired damage is not passed on.

 

 

 

Telomerase activity is involved with stem cells/tissue repair and I haven't written about that yet but basically, with the reduction of the stem cell pool, therapies will be needed to replenish that and that would replenish the telomeres of those new stem cells but fr the most part it seems that evolution used telomere controlled senescence as a means of prevent diseases like cancer that results from cells that build up to much damage (genetic/nongenetic).

 

Telomere shortening is not the only way to induce cellular senesence. http://www.ncbi.nlm.nih.gov/pubmed/15734683 by Campisi (2005). DNA damage can lead to senesence also. It might be that those therapies can get past the potential problem as senesence can still be induced appropriately after accumulation of too much damage, I'm not sure how redundant the functions are.

Edited January 14, 2013 by jp255

[Inkstersco]

Note that the site at www.sens.org has been recently redone with extra info on the seven damage forms.