Why do you get old and ultimately die

People always assume you get old and you just die. if i slice my arm open, it will heal and eventually my arm will be good as new. Why don't organs heal themselves as well, and would this be the key to eternal life if you exclude disease. Is oxygen the primary culprit?

One of the primary ingredients is the telomere. Every chromosome is decorated on both ends with a length of repetitive DNA. Each time a cell divides, some of the telomere is cut from the ends. Eventually, the cell cannot divide further.

http://www.telomere.net/

- Warren

Senescence researchers who believe that telomeres play a major role in human senescence are in a minority, Chroot. What do you think about glycation and mitochondrial DNA degradation?

i don't know if i agree with that article. so we are either to die of cancer or cells that can't fix themselves...

I thought something had come out to disprove the telomere theory. But I can't recall when or where, so I might be wrong on that. Either way, it's not something that consensus has been reached on; remains only one of many theories.

oldunion, you pretty much summed it up: cells that can't fix themselves. The big question about aging is why do cells lose the ability to fix themselves?

If I may speculate a bit, as cells differentiate and mature in the developing human, they go through different stages and different genes and production of proteins are turned on or off. So, enough cells may reach a "mature" stage without enough remaining to replenish them from precursors but just from already mature cells (we know that stem cell precursors do diminish with age), so every time a cell divides, you have another chance for a mistake in that process that diminishes its function (in whatever way that might be happening). Or, alternatively, the progression along developmental stages may, in a simple way of looking at it, be a one-way process that once you go past a certain point, there's no turning back to that rapid ability to grow organs as we had as infants and children.

Moonbear said:

I thought something had come out to disprove the telomere theory. But I can't recall when or where, so I might be wrong on that. Either way, it's not something that consensus has been reached on; remains only one of many theories.

oldunion, you pretty much summed it up: cells that can't fix themselves. The big question about aging is why do cells lose the ability to fix themselves?

If I may speculate a bit, as cells differentiate and mature in the developing human, they go through different stages and different genes and production of proteins are turned on or off. So, enough cells may reach a "mature" stage without enough remaining to replenish them from precursors but just from already mature cells (we know that stem cell precursors do diminish with age), so every time a cell divides, you have another chance for a mistake in that process that diminishes its function (in whatever way that might be happening). Or, alternatively, the progression along developmental stages may, in a simple way of looking at it, be a one-way process that once you go past a certain point, there's no turning back to that rapid ability to grow organs as we had as infants and children.

sounds similar to the telomere theory i just read in the aforeposted link.

oldunion said:

sounds similar to the telomere theory i just read in the aforeposted link.

Generally, yes, I'm not venturing into too wild of speculation. I hadn't read the telomere link. But, I'm leaving it open that there may be other ways besides telomere shortening that could lead to the same outcome, because that's pretty much where current debate leaves it open-ended.

*Warren backs out slowly, since he's over his head*

- Warren

Our cells are basically 'programmed' to die - this process is called apoptosis [wikipedia link]. Though exactly why and when cells get a 'death' sentence is, I believe, still under investitation. The problem with cancerous cells is that they ignore these signals and keep growing unabated. It is a big area of research, being a pretty important function and its possible implications towards treatment and cures for cancer, and there is still much that is not known.

Alot of people who aren't molecular biologists like Ray Kurzweil would have you believe that immortality is right around the corner, but until a respected person in the field comes out and says its possible, I'm not holding my breath.

If you are truly interested the Febuary issue of Cell February 25, 2005: 120 (4) deals entirely with aging. The grand review describes 4 different theories.

1. Somatic mutation theory: In essence, longer lived individuals typically have higher levels of a protein known as "poly(ADP-ribose) polymerase-1 (PARP-1)" that is involved in stress induced DNA damage repair. Individuals with higher levels of this protein have a positive correlation with longer life

2. Telomere loss theory: The ends of the chromosome known as telomeres get shorter and shorter from subsequent cell divisions because the replicating machinery cannot read to the end without a protein known as "telomerase". Eventually the cell ceases it's ability to replicate. Interestingly, oxidative stress may even enhance telomere loss compared to just the normal loss rate.

3. Mitochondrial Theory
As you age you accumulate mutations in mitochondrial DNA which eventually prevents its production of the protein cytochrome c oxidase (necessary for your cells to produce ATP by respiration) This causes muscle (and other tissues) to have lower "bioenergenesis" or ability to produce ATP and therefore function correctly.

4. Altered proteins/waste accumulation theory
as you age your ability to turn over proteins and make new ones decreases. This leads to waste accumulation of proteins. Your cellular garbage disposals (proteasomes and hydrolases) actually decrease in function as you age. They think this the reason for Alzheimer's, Parkinson's, cataracts and others...

5. The Network theory of aging
As you can guess this is essentially the above mechanisms but also involves cells and organ system communication. When one organ system begins to age, it may actually signal to the entire organism to age. Higher levels of reactive oxygen species (produced from normal day-to-day life in our cells) may enhance telomere loss and reduce proteasome activity. It may also cause an aging cells or cell system to secrete a hormone that signals to other cells it's time to age.

These are the leading theories. Most of this is plagerized from the review
Kirkwood. Understanding the Odd Science of Aging. Cell 120(4) 437-447
And like I said the whole issue is dedicated to aging. It's really fascinating. It also talks about how caloric restriction can slow the aging process and make you live longer. (Of course it also makes you hungry all the time and hate life so maybe it's not the perfect solution but it is the only scientifically proven method to prolong your life)

CR vs PBN in regards to extension of maximum species lifespan

Mr.V. said:

It also talks about how caloric restriction can slow the aging process and make you live longer. (Of course it also makes you hungry all the time and hate life so maybe it's not the perfect solution but it is the only scientifically proven method to prolong your life)

Whether science can prove things or not is a philosophocal question, but there are many things that have been shown to be accountable of for variance in lifespans between various groups of humans.

In terms of extending maximum species lifespan, CR is more alone, but it has to share the stage with spin traps such as PBN and its chemical relative N-tert-butyl-hydroxylamine (NtBHA).

so-crates said:

Alot of people who aren't molecular biologists like Ray Kurzweil would have you believe that immortality is right around the corner, but until a respected person in the field comes out and says its possible, I'm not holding my breath.

http://www.kronosinstitute.org/seminars/seminar-2002-02-08-deGrey.html

--
Biotechnological advances in the past few years have made it possible to design interventions to reverse or obviate all these changes, and thereby to break the link between metabolism (being alive) and pathology (being dead). This should be achievable in mice within ten years
--

(Aubrey de Grey, Ph.D.
Research Associate
Department of Genetics
University of Cambridge Cambridge, UK)

so-crates said:

Our cells are basically 'programmed' to die - this process is called apoptosis [wikipedia link]. Though exactly why and when cells get a 'death' sentence is, I believe, still under investitation.

Apoptosis is only one form of cell death. Yes, it does involve specific signals and events that trigger cell death, and involves intermediates that can be measured, but the reason we need to be able to measure these signals is because there are other ways cells die that are not apoptotic.

I don't think oxidative stress has been mentioned yet. Oxygen forms free radicals, which attacks our biomolecules and damages them. I've heard that people living at high altitudes live longer, and it has been sufficiently proven that reduced metabolic stress increases life time of an organism.

Longevity in mammals

Life span varies among species.
One approach to the study of these differences is the use of dimensional analysis to stablish comparisons.
More recently, telomerase activity was related to number of cell generations in humans and some experimental models.
What would be the main factors involved in the differences in longevity among mammals?

What?! That is strange and very interesting. I thought your body only got free radicals from your diet.

~Kitty

I just saw an item in Science that proteins lurching around in cells can disturb the electron clouds and produce free radicals.

NtBHA

misskitty said:

I thought your body only got free radicals from your diet.

Mitichondrial respiration naturally produces radicals. This is why life extensionists ingest spin traps such as NtBHA and PBN. With too much or too little oxygen present, radical generation is greatly increased. Every time you excercise, you greatly increase your production of radicals.

hitssquad said:

Mitichondrial respiration naturally produces radicals. This is why life extensionists ingest spin traps such as NtBHA and PBN. With too much or too little oxygen present, radical generation is greatly increased. Every time you excercise, you greatly increase your production of radicals.

i find it curious that not only does respiration occur in mito, but the apoptotic pathway is initiated there.

The apoptotic pathway? What's that?

~Kitty

Has anyone thought of studying why turtles can get so incredibly ancient (200-250 years from what I know)?
Although they are reptiles, rather than mammals, perhaps one might find some interesting clues here?

This wikipedia article might be able to answer part of that: http://en.wikipedia.org/wiki/Turtle

I don't know if that helps. Some of the links out of that article might be of some use.

~Kitty

oldunion said:

if i slice my arm open, it will heal and eventually my arm will be good as new.

Coming from personal experience -- it seems like the older I get, the longer superficial wounds take to heal. I am not sure about the "good as new" part of your sentence. As I get older I feel that physical trauma becomes less reversible somehow.

It probably has to do with the dimished ability of your cells to heal because of the age factor mentioned earlier.

~Kitty

misskitty said:

It probably has to do with the dimished ability of your cells to heal because of the age factor mentioned earlier.

That would explain it. How does physics come into this? (Chemistry is physics, isn't it?)

I'm not sure how physics would come into this process. This is more of a chemical thing I would think.

~Kitty

The older you are the more likely you have acquired mutations. These mutations are not going to be the same in every cell. Therefore one can see how complicated things can get since cells in a multicellular organisms are supposed to work in complete synchronization. If mutations that are not expected begin to accumalate in different cells and in different areas one can see the possibly dire consequences.

misskitty said:

The apoptotic pathway? What's that?

~Kitty

Apoptosis is Programmed cell death and it can be initiated by the mitochondria when certain signals are present.

Read
http://en.wikipedia.org/wiki/Apoptosis