Why living things age and die?

[Improvision]

All the cells in your body are replaced when they die. When your body is replacing cells, why would cells in our "youthful" bodies be replaced over time by NEW cells that make up our "aged/old" bodies, which are not as good as the cells that were there before? Why do living things just come to a grinding halt in "death"?

[MM6]

There are several threads around here at the moment that deal with aging (search-->aging).

 

You have some misconceptions. Just to start, stem cells are the cells that replace other cells. Stem cells have a lifespan too, although it's much longer than fully differentiated cells (cells that have been produced and develop for a specific function, e.g. cardiomyocytes (heart cells)).

 

Much of this has to do with telomeres (the "cap" on the end of chromosomes that gets progressively shorter with each DNA replication/cell division). After a point the chromosome becomes damaged (missing base pairs b/c it's losing at both ends) and senescence machinery within the cell clicks on-->cell dies nicely.

 

There are other intracellular and cell/tissue environment factors, too. But the gist is, stem cells age and die. That's our maximum life span.

 

Also to make it clear, as stem cells age they become more inactive and also produce cells with certain hallmarks of age. So as we age, our stem cells are producing cells that are not as fresh as they once did. And our cells' support structure (extracellular matrix) is not as fresh. Thus, we slowly begin to look like a dried up leaf.

Edited May 26, 2009 by MM6

[granpa]

There are several threads around here at the moment that deal with aging (search-->aging).

 

You have some misconceptions. Just to start, stem cells are the cells that replace other cells. Stem cells have a lifespan too, although it's much longer than fully differentiated cells (cells that have been produced and develop for a specific function, e.g. cardiomyocytes (heart cells)).

 

Much of this has to do with telomeres (the "cap" on the end of chromosomes that gets progressively shorter with each DNA replication/cell division). After a point the chromosome becomes damaged (missing base pairs b/c it's losing at both ends) and senescence machinery within the cell clicks on-->cell dies nicely.

 

There are other intracellular and cell/tissue environment factors, too. But the gist is, stem cells age and die. That's our maximum life span.

 

Also to make it clear, as stem cells age they become more inactive and also produce cells with certain hallmarks of age. So as we age, our stem cells are producing cells that are not as fresh as they once did. And our cells' support structure (extracellular matrix) is not as fresh. Thus, we slowly begin to look like a dried up leaf.

telemeres?

 

then why do single celled organisms live forever.

 

why are our gametes not likewise effected?

[scrappy]

All the cells in your body are replaced when they die. When your body is replacing cells, why would cells in our "youthful" bodies be replaced over time by NEW cells that make up our "aged/old" bodies, which are not as good as the cells that were there before? Why do living things just come to a grinding halt in "death"?

Here’s a hypothetical shot at it. It’s because of sex. Sex, according to W. D. Hamilton, enables a genome to escape its genetic parasites. But to do that the genome must leap from one generation to the next. That means the preceding generation must die. As such, genomes do a much better job of staying alive than organisms do. (And the fact that they are digital makes one hell of a difference!)

[cameron marical]

Why can our bodys not make new stem cells after the originalls die?

 

And what is the role that antioxidants play In the aging process?

[granpa]

Why can our bodys not make new stem cells after the originalls die?

 

And what is the role that antioxidants play In the aging process?

THATs the question!

[cameron marical]

I am responding to mm6's information, And I did not read any mention of antioxidants In the OP's question.

[granpa]

I am responding to mm6's information, And I did not read any mention of antioxidants In the OP's question.

chill out. I was agreeing with you.

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There are several threads around here at the moment that deal with aging (search-->aging).

 

You have some misconceptions. Just to start, stem cells are the cells that replace other cells. Stem cells have a lifespan too, although it's much longer than fully differentiated cells (cells that have been produced and develop for a specific function, e.g. cardiomyocytes (heart cells)).

 

Much of this has to do with telomeres (the "cap" on the end of chromosomes that gets progressively shorter with each DNA replication/cell division). After a point the chromosome becomes damaged (missing base pairs b/c it's losing at both ends) and senescence machinery within the cell clicks on-->cell dies nicely.

 

There are other intracellular and cell/tissue environment factors, too. But the gist is, stem cells age and die. That's our maximum life span.

 

Also to make it clear, as stem cells age they become more inactive and also produce cells with certain hallmarks of age. So as we age, our stem cells are producing cells that are not as fresh as they once did. And our cells' support structure (extracellular matrix) is not as fresh. Thus, we slowly begin to look like a dried up leaf.

the way I see it, nonstem cells are cheap disposable mass produced specialized cells that lack any cellular machinery that isnt essential. that includes the machinery to keep the telemeres the right length. so they can only reproduce so many times before they die.

[Improvision]

Why do telemeres get shorter?

[iNow]

http://mcb.berkeley.edu/courses/mcb135k/telomeres.html

Telomere shortening - the end replication problem

 

• Telomeres shorten with each cell division (S phase)
  
  
  • The "end replication" problem:
    
    
    • DNA replication is bidirectional
      
      
    • DNA polymerases are unidirectional
      
      
    • DNA polymerases must initiate replication from a primer

  [*]Therefore: each round of DNA replication leaves 50-200 bp DNA unreplicated at the 3' end
  [*]Cells with telomeres that are 10-12 kb in length (average) divide 50-60 times
  • Telomeres are 4-6 kb [5-7 kb] in length (average)
  [*]Cellular senescence is triggeredwhen telomeres are on average 4-6 kb

 

 

http://en.wikipedia.org/wiki/Telomere#Systemic_telomere_length_and_aging

As a measure of systemic telomere length, generally, peripheral blood leukocyte telomere length is preferred. Systemic telomere length has been proposed as a marker of biological aging. A subject's systemic telomere length is predominantly genetically determined, but has several other known determinants: age (shorter telomeres in older people), paternal age at birth (longer telomeres in subjects with older fathers at their birth) and sex (shorter telomeres in men, probably due to a faster telomere attrition). Evidence suggests that elevated levels of oxidative stress and inflammation further increase the telomere attrition rate.[8]

 

Vitamin D may have an effect on peripheral blood leukocyte telomere length. Richards and coworkers examined whether vitamin D concentrations would slow the rate of shortening of leukocyte telomeres. The authors stated that vitamin D is a potent inhibitor of the proinflammatory response and slows the turnover of leukocytes. Leukocyte telomere length (LTL) predicts the development of aging-related disease, and length of these telomeres decreases with each cell division and with increased inflammation. Researchers measured serum vitamin D concentrations in 2160 women aged 18–79 years (mean age: 49.4) from a large population-based cohort of twins. This study divided the group into thirds based on vitamin D levels, and found that increased age was significantly associated with shorter LTL (r = -0.40, P < 0.0001). Higher serum vitamin D concentrations were significantly associated with longer LTL (r = 0.07, P = 0.0010), and this finding persisted even after adjustment for age (r = 0.09, P < 0.0001) and other variables that independently could affect LTL (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity). The difference in LTL between the highest and lowest tertiles of vitamin D was highly significant (P = 0.0009), and the authors stated that this was equivalent to 5.0 years of aging. The authors concluded that higher vitamin D levels, (easily modifiable through nutritional supplementation), were associated with longer LTL, which underscores the potentially beneficial effects of vitamin D on aging and age-related diseases.

 

 

Long story short... They get shorter because they divide.

[CharonY]

Also it is a regulatory mechanism. Single cell organism can divide and proliferate basically endlessly. However, within a larger multicellular organism this will cause detrimental effects as manifested in tumors. In the end it is likely a trade-off.

[Improvision]

http://mcb.berkeley.edu/courses/mcb135k/telomeres.html

Telomere shortening - the end replication problem

 

• Telomeres shorten with each cell division (S phase)
  
  
  • The "end replication" problem:
    
    
    • DNA replication is bidirectional
      
      
    • DNA polymerases are unidirectional
      
      
    • DNA polymerases must initiate replication from a primer

  [*]Therefore: each round of DNA replication leaves 50-200 bp DNA unreplicated at the 3' end
  [*]Cells with telomeres that are 10-12 kb in length (average) divide 50-60 times
  • Telomeres are 4-6 kb [5-7 kb] in length (average)
  [*]Cellular senescence is triggeredwhen telomeres are on average 4-6 kb

 

 

http://en.wikipedia.org/wiki/Telomere#Systemic_telomere_length_and_aging

As a measure of systemic telomere length, generally, peripheral blood leukocyte telomere length is preferred. Systemic telomere length has been proposed as a marker of biological aging. A subject's systemic telomere length is predominantly genetically determined, but has several other known determinants: age (shorter telomeres in older people), paternal age at birth (longer telomeres in subjects with older fathers at their birth) and sex (shorter telomeres in men, probably due to a faster telomere attrition). Evidence suggests that elevated levels of oxidative stress and inflammation further increase the telomere attrition rate.[8]

 

Vitamin D may have an effect on peripheral blood leukocyte telomere length. Richards and coworkers examined whether vitamin D concentrations would slow the rate of shortening of leukocyte telomeres. The authors stated that vitamin D is a potent inhibitor of the proinflammatory response and slows the turnover of leukocytes. Leukocyte telomere length (LTL) predicts the development of aging-related disease, and length of these telomeres decreases with each cell division and with increased inflammation. Researchers measured serum vitamin D concentrations in 2160 women aged 18–79 years (mean age: 49.4) from a large population-based cohort of twins. This study divided the group into thirds based on vitamin D levels, and found that increased age was significantly associated with shorter LTL (r = -0.40, P < 0.0001). Higher serum vitamin D concentrations were significantly associated with longer LTL (r = 0.07, P = 0.0010), and this finding persisted even after adjustment for age (r = 0.09, P < 0.0001) and other variables that independently could affect LTL (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity). The difference in LTL between the highest and lowest tertiles of vitamin D was highly significant (P = 0.0009), and the authors stated that this was equivalent to 5.0 years of aging. The authors concluded that higher vitamin D levels, (easily modifiable through nutritional supplementation), were associated with longer LTL, which underscores the potentially beneficial effects of vitamin D on aging and age-related diseases.

 

 

Long story short... They get shorter because they divide.

So DNA is just not exactly replicated, because telomeres are not regenerated which results in telomeres being basically cut in half. How are telomeres obtained and why aren't they replaced/repaired?

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Also it is a regulatory mechanism. Single cell organism can divide and proliferate basically endlessly. However, within a larger multicellular organism this will cause detrimental effects as manifested in tumors. In the end it is likely a trade-off.

Couldn't the division of cells be regulated, so that it can be done indefinitely without detrimental effects?

[cameron marical]

ok. so what can we do to stop telemores shortening from happening?

 

Does anyone know what SENS has done with this?

 

chill out. I was agreeing with you.

 

oh, My bad.

[GDG]

ok. so what can we do to stop telemores shortening from happening?

 

Probably nothing. Telomeres get shorter as a necessary consequence of the way that chromosomes are replicated. You can slow down the process by not undergoing as cell divisions as rapidly -- this is probably the mechanism by which calorie restriction extends life. Or, you can "reset" the telomeres periodically by inducing the enzyme (telomerase) which adds the telomeres to germ cells.

 

Tumor cells that have become "immortalized" typically have activated their telomerase. This illustrates one of the potential side effects of resetting your telomers...

[MM6]

Does anyone know what SENS has done with this? [oxidative stress]

 

Here's a list of de Grey's publications. Most look like review papers. A lot are available directly in PDF.

 

http://www.sens.org/index.php?pagename=mj_sens_scientific

 

Scroll down to Mitochondrial mutations and their effects:

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His interest in telomeres/telomerase seems directed mostly at cancer prevention/therapy (getting telomeres to shorten in cancer cells). Search for telomere within the body of the webpage.

Edited May 30, 2009 by MM6
Consecutive posts merged.

[ennui]

There are some very good points about telomeres here. But another aspect of the age issue is the environment. While we may have it hard-wired in our genomes to have our telomeres shortened, etc. there is also the environment and how it affects our DNA.

 

Our cells are constantly exposed to breakages and other kinds of damage. The mechanisms we have to repair the DNA aren't perfect. One of them, non-homologous end joining, can result in bits of the DNA being trimmed (e.g. by the enzyme Artemis, or other nucleases) or even bits of the DNA being added in a template-independent manner in microhomology sticky-ends (e.g. TdT and DNA polymerase mu).

 

So as we live, we accumulate more damage to our DNA. Eventually, the damage is such that it escapes the cell's repair mechanisms (these being imperfect) and we get loss-of-function of certain proteins. This results in ageing and cancer.