DNA damage and reproduction

[lister]

I've recently been reading a little about the process of ageing. Now I hvae very little biological knowledge, so a lot of it is double dutch to me, but I gather one of the causes of aging is DNA getting "damaged" as cells reproduce.

So my (no doubt simplistic) question is: If DNA damage over our lifetimes causes us to age, how is it that the DNA used to create offspring is "OK" again? (eg our children are young and healthy, and do not have wrinkled skin / liver spots whatever?)

[Cuddles]

The DNA damage they speak of is the telomeres at the end of the strands. This doesn't actually do anything except sit at the end as a sort of buffer to stop the rest of it getting damaged. When a cell reproduces, the telomeres of the daughter cells are shorter than that of the parents. It is also possible, although not proven, that it can act as a sort of clock, either by the actual length being read or by simply running out and active DNA being damaged. However, this process is repairable and ever reversible. Some things have processes that either prevent the telomeres wearing down or fix them, and so they can effectively live forever, in the abscence of anything else that causes aging. Humans mostly don't do this, but the germ cells are an exception. When eggs and sperm are produced, they are produced with full length DNA and so can start again from scratch. This is thought to be one of the reasons cloning has problems, since you start with old DNA it does not act exactly the way young DNA would, although the problems aren't as obvious as children being born old and wrinkly.

[Asolepius]

You ask a very good question! Where do I start? Well, there are two main cell lines, somatic and germline. Germline cells are eggs and spermatozoa, somatic cells are all the rest. They both of course divide very many times during a lifetime, and DNA gets damaged because of copying errors and external things like radiation and chemicals. But the cells have very effective repair mechanisms - good but not perfect. Yes, it has been argued that aging is due to an `error catastrophe', but it's not a fully defined area. If it happens, it affects the somatic cells more than the germline cells. It's interesting to note that eggs in humans don't divide after birth of females - they start life with all the eggs they are ever going to produce. Males of course produce spermatozoa in vast numbers throughout life. It's been observed that genetic problems like Down's syndrome increase in frequency with the age of fathers, but not with age of mothers, so damage does seem to accumulate in the germline but it's different from somatic cell damage. Or at least the outcome is different. But the bottom line is that effects of age you see, such as wrinkles etc, are manifestations of somatic cells and not germline cells, so won't be passed on. I suggest you read `The Language of the Genes' by Steve Jones. Good stuff and quite accessible to the lay reader.

BTW I am not a geneticist and I'm quite prepared to be shot to bits over my explanation!

[Capsid]

By damage, do you mean telomere shortening (http://en.wikipedia.org/wiki/Telomere)? Telomere shortening does not occur in germ cells however because of the presence of telomerase, therefore the full length chromosomes are inherited by the offspring.

ETA: beaten to it!

[lister]

OK, I'm confused now :D

If telomeres are simply buffers that gradually get shorter, then why would this affect physical appearance?

Or are the physical effects of ageing due to other factors?

[aggle-rithm]

OK, I'm confused now :D

If telomeres are simply buffers that gradually get shorter, then why would this affect physical appearance?

Or are the physical effects of ageing due to other factors?

I've heard that oxygen is the culprit. It was actually fairly late in evolution that organisms learned how to tolerate oxygen enough to actually use it as an energy source, but it still does damage over time.

[Capsid]

OK, I'm confused now :D

If telomeres are simply buffers that gradually get shorter, then why would this affect physical appearance?

Or are the physical effects of ageing due to other factors?
The telomere can only shorten so much after that time the cell stops dividing and will age.

[casebro]

Then to complicate things, our mitochondria have their own genes. 10,000 vs 40,000 in out nucleuses. I think it is these genes that 'age'. They lack the repair mechanisms of the nuclear genes. So our mitochondria do age, causing cellular aging. Plus, we only get our mitochondria from our mothers, so we have some maternally transmitted traits. Mostly metabolic, but with overlap into cell lifespans, since it is the mitochondria that program cell lifespan. It is in the mito's that the oxygen/anti-oxidants have thier effects. Too bad they don't really have it figured out yet. I have a problem with that system. Oxidative phosphorisation? So does umm the guy before Lance Armstrong, Greg LeMonde. You get old, your mito's don't oxidise fats so well, you lose endurance. You build up oxidation radicals that cause cancer?...

[Pro7]

Read that Telomerase can be "modified" to produce longer lifespan. Telomere and Telomerase is slightly different. Telomerase is a enzyme as a byproduct?

http://en.wikipedia.org/wiki/Telomerase

In my opinion, I believe that telomerase can be altered to give out specific but more concentrated form of enzymatic structure that could increase the longevity.

[Pro7]

Then to complicate things, our mitochondria have their own genes. 10,000 vs 40,000 in out nucleuses. I think it is these genes that 'age'. They lack the repair mechanisms of the nuclear genes. So our mitochondria do age, causing cellular aging. Plus, we only get our mitochondria from our mothers, so we have some maternally transmitted traits. Mostly metabolic, but with overlap into cell lifespans, since it is the mitochondria that program cell lifespan. It is in the mito's that the oxygen/anti-oxidants have thier effects. Too bad they don't really have it figured out yet. I have a problem with that system. Oxidative phosphorisation? So does umm the guy before Lance Armstrong, Greg LeMonde. You get old, your mito's don't oxidise fats so well, you lose endurance. You build up oxidation radicals that cause cancer?...

Mitrochondria is a "power plant" of a cell. Yes it does degrade at each reproduction "copies" of new cells. If there is a technology to "measure" such degradation, then scientists may be able to determine a person's lifespan.

[Pro7]

http://en.wikipedia.org/wiki/Telomerase#Telomerase_as_a_potential_drug_target

Cancer is a very difficult disease to fight because the immune system cannot recognize it, and cancer cells are immortal; they will always continue dividing.

>Thats the first sentence indicated in that url. I strongly disagree that cancer cells are immortal.

This is my opinion:

All replicating cells use "membranic action" in order to divide and replicate. If scientists were to find a way to halt specific membranic action of cancer cells, then a solution would be developed. I really think that scientists are wasting their time experimenting on telomerase formulas.

[Pro7]

http://news.nationalgeographic.com/news/2003/02/0224_030224_DNAcomputer.html

Maybe "Dna computers" can assist in fighting cancer cells?

[Dymanic]

Mitrochondria is a "power plant" of a cell. Yes it does degrade at each reproduction "copies" of new cells. If there is a technology to "measure" such degradation, then scientists may be able to determine a person's lifespan.
If you get an afternoon free sometime, maybe you can figure out some simple way to rig a couple of mitochondria together so as to eliminate the need for oxygen in cellular metabolism.

[kellyb]

>Thats the first sentence indicated in that url. I strongly disagree that cancer cells are immortal.


You're misunderstanding the use of the word "immortal" in this context. They don't mean "Immortal like Jesus".

[Pro7]

You're misunderstanding the use of the word "immortal" in this context. They don't mean "Immortal like Jesus".

Yes right.. its easy to misunderstand that simple word when its being used in that sentence. "immortal" meant by "permanent" or "continous" and that is what I disagree....

[Pro7]

If you get an afternoon free sometime, maybe you can figure out some simple way to rig a couple of mitochondria together so as to eliminate the need for oxygen in cellular metabolism.

nothing is simple in microbiology.

[Roboramma]

As well as what others have said, let's look at what happens when the kind of damage that occurs in somatic cells and causes some of the symptoms of aging happen to germ-line cells.

What sort of symptom would we expect? Well, the cell might fail completley, or lose fertility to the point that it simply isn't capable of assisting in the creation of another organism. All we'd notice from this is a loss of fertility - which happens to be one of the signs of aging.

The cell, on the other hand, might retain it's ability to produce offspring but have some other problems that would manifest themselves in that offspring. This could be in the form of a mutation that's passed on. Okay, so what happens when negative mutations are inherited? They tend to be selected against in the population.

Then again, there's always a chance that the mutation was positive, in which case it would be selected for (obviously).

All this goes to actual damage to the DNA.

[blutoski]

I've recently been reading a little about the process of ageing. Now I hvae very little biological knowledge, so a lot of it is double dutch to me, but I gather one of the causes of aging is DNA getting "damaged" as cells reproduce.

So my (no doubt simplistic) question is: If DNA damage over our lifetimes causes us to age, how is it that the DNA used to create offspring is "OK" again? (eg our children are young and healthy, and do not have wrinkled skin / liver spots whatever?)

As pointed out, your confusion is actually quite reasonable, because you are missing some pieces of the picture regarding the mechanism of aging.

Firstly, the 'cause' of aging is not completely understood. Some animals do not have what we'd call senescence - they die when they're eaten or damaged mechanically (burned, crushed, &c), or get an infectious disease. Hydras are an example of an animal that does not 'grow old'. There appear to be genes that direct aging and eventual death.

Two mechanisms that are relevant are: genetically-programmed endocrine changes over our lifetime (eg: hormone production) and telomeres. A fourth is the accumulating damage such as scarring and cellular mutations. The impact of this last family of effects varies with the magnitude of the damage.

In terms of telomeres - yes, this is considered to be quite important. The way it contributes to 'aging' is that the cell lines stop dividing after a certain number of generations. This means that as neighbouring cells die, there are fewer cell lines to replace them in the tissue. Over time, the effectiveness of the tissue/organ is diminished, their function is impaired and they ultimately just fail.

Telomerase is an enzyme produced in some animals, and humans do have a gene for it. It elongates telomeres in cells, extending the number of generations the cell can divide. Telomerase genes 'turn off' in humans early in our life shortly before or after birth. (this is related to the endocrine and genetic programming I mentioned above - in other words, our species has evolved to do this for some reason) Telomerase therapy has been tried in some animals, but the challenge appears to be to get telomerase into every cell in a reasonable quantity, without it being spread unevenly or just plain digested/metabolized outside the cell membranes. I personally think it's a credible direction for research right now.

(aside: telomerase appears to be a very primitive enzyme - it has an rna component!)

(also aside: telomerase is not manufactured from the telomere genetics - telomeres are not coding for genes. They are just the little plastic tips on the end of our genetic shoelaces. Telomerase is coded in two parts, on two chromosomes, nowhere near their end positions.)

Your question about germ cells (egg and sperm) and why they don't have the accumulated damage of the parent is also a good one. Here's the short answer: many do have damage.

The misunderstanding is that in the grand scheme of things, the number of cells in our body that are actually damaged genetically by normal living conditions is pretty small anyway. Think about skin cancer, for example: your skin cells have damage-repair mechanisms that repair most of the dna problems before the cell divides. But every once in awhile one in a quadrillion is missed, and over sixty years of nude sunbathing, we get skin cancer from one botched cell.

The germ cells are even more protected from external mutagens than our skin, so their mutations are rarer. Nevertheless, every embryo has on average six de novo mutations (mutations that mean the offspring has a mutation the parents didn't give it). The most common cause is probably retrotransposon insertion, but karyotype mutations are also common. My biology teacher showed us her karyotype in comparison to her parents once - she clearly has an inverted segment in one chromosome that must have happened during her mother's egg production. If the mutation is serious, the embryo fails. This is one reason so few fertilizations develop, are born, and live to be 1 year old.

The female body also seems to be able to juggle eggs for quality, sending out the healthiest first. This is one reason that congenital problems are more likely if the mother is older. Eg: autism.

So, while there are all these mutations in offspring, the cell nevertheless starts up with the ability to produce telomerase and extend the telomeres, so the newborn can expect a normal lifespan.

Confirmation of this cause-of-aging hypothesis is very persuasive. There are two ways we can see examples of offspring born with telomerase production anomalies, and the effect on lifespan.

1. cloning from adult cells - one concern with cloning a newborn from an adult cell is that the originating cell did not have a full complement of telomere remaining. It would have, say, half a lifetime's worth. Indeed, cloned animals - such as Dolly - have proven to have short lifespans. They age prematurely. They may not have the genetic capacity in their adult genetics to activate telomerase production in the embryo.

2. premature aging diseases are associated with telomerase gene mutations - children with some variants of Werner Syndrome and some other conditions look like old men/ladies before their premature deaths by around ten years old.

[Dr. Imago]

Nice post, Blutoski.

I'd only also add that there are certain "apoptosis" genes that turn on when complex cellular mechanisms reach certain thresholds. These genes actually cause the cell to die. This is also part of the "cellular fatique" that activates cell death. Certain cell lines will live for only a certain number of divisions, and other times cellular damage results in the activation of these apoptotic genes. Great work has been undertaken about how to understand these mechanisms, across a broad spectrum of cellular lines, as well.

-Dr. Imago

[casebro]

Yes, but my understanding is that much of the body does not work by Metosis.

Rather than splitting old cells into two new ones, much of the body has 'stem cells' hanging around, waiting to be activated. They have been waiting since birth/childhood. Muscles, as a frinstance, have three kinds of cells- White cells that burn sugar, for quick energy. Red cells, that burn fat, for enduring power. And stem cells that can become either red or white, depending on what kind of excercise your body needs more of. So, as you age, your body components eventually run out of the stem cells that have been on standby.

I dunno what parts use Metosis. I think it's skin, bones and intestines. But I think nerves, brain(?),....don't, they depend on stem cells. Hence all the interest these days in stem cell research, particularly towards spinal injuries. I'm unclear on other organs. And I haven't caught the name for the 'stem cell based' repair function...

And I'm guessing that my life long mito disease has run my muscles out of stem cells. I no longer seem to gain endurance from exercise. The best I do is recover. Worst case is myoglobinuria and kidney casts, which means I've killed cells, and have less to use in the future.

ETA, Deja Vu! Or mumerology, er somethin. (coincidence, maybe?) Me and Dr Imago each have 1211 post as of this second.

[blutoski]

Yes, but my understanding is that much of the body does not work by Metosis.

Rather than splitting old cells into two new ones, much of the body has 'stem cells' hanging around, waiting to be activated. They have been waiting since birth/childhood. Muscles, as a frinstance, have three kinds of cells- White cells that burn sugar, for quick energy. Red cells, that burn fat, for enduring power. And stem cells that can become either red or white, depending on what kind of excercise your body needs more of. So, as you age, your body components eventually run out of the stem cells that have been on standby.

I dunno what parts use Metosis. I think it's skin, bones and intestines. But I think nerves, brain(?),....don't, they depend on stem cells. Hence all the interest these days in stem cell research, particularly towards spinal injuries. I'm unclear on other organs. And I haven't caught the name for the 'stem cell based' repair function...

I find your post confusing. I think you mean 'mitosis'. Most cells in the body are somatic - they divide by mitosis. That is also how stem cells work - they just divide in half by mitosis. The only cells that don't are germ cells - that is: cells that produce sperm and egg.

My research, for example, involves propagating cell lines of white blood cells. These are immortal cell lines derived from tumours, and they reproduce mitotically, theretically forever. One of the carcinogenic mutations that makes this possible is the activation of controller genes for expressing telomerase.


Note:
I'm pretty sure you've got the 'coloured' muscle cells thing mixed up with something else. I think you're talking about muscle fibres, such as Type I, IIa and IIb. These types can and do coexist in the same muscle cell, although different cells will have different proportions.


re: nerve cells and stem cell research. There's a difference between stem cells versus undifferentiated tissue cells. There is some evidence that adults may have a few stem cells, but it's weak and controversial. What is not controversial is that we have a lot of undifferentiated cells whose role is to act as points of origin for tissue regeneration. However, undifferentiated cells that can turn into nerve cells to repair damaged nerves are either rare or nonexistent. This is why a dead nerve does not regenerate the same way a dead blood vessel can. This type of damage is basically unfixable. The quest for stem cells is especially important to nerve-damaged patients for this reason.

[casebro]

Teacher, my hand is up:

I find your post confusing. I think you mean 'mitosis'.

Sorry if my phonetic mis-spelling confused you. My proof reading missed it.

Most cells in the body are somatic - they divide by mitosis. That is also how stem cells work - they just divide in half by mitosis. The only cells that don't are germ cells - that is: cells that produce sperm and egg.

What about red blood cells, that don't reproduce, but are made in bone marrow? What is the name for that type of reproduction?

Skin cells, muscle cells, and red blood cells each have a slightly different way of reproducing. I don't know the nomenclature. I'm better with concepts than names. (duh!) Skin, bone, and intestinal cells are constantly reproducing, without stem cells. They need to, they suffer constant wear. Red blod cells are produced by other cells, that are not red blood cells. Muscle cells come from a fixed source of stem cells, that will be differentiated into different types of muscle. I know that these different systems of production are important in biopsys, since the cellular genes are replicated from different pathways.

It's also why we have lots more cancers in skin, bone, and intestines than we do in muscles and nerves. I.E., those cells which are reproduced from other identical cells suffer more mutations. Those cells produced from a cloistered genetic source get fewer mutations, but are slower to be produced.


Note:
I'm pretty sure you've got the 'coloured' muscle cells thing mixed up with something else. I think you're talking about muscle fibres, such as Type I, IIa and IIb. These types can and do coexist in the same muscle cell, although different cells will have different proportions.

I think muscles have fibers, fibers have cells. Red Fibers have fat-burning cells, White fibers have sugar burners. Mitochindria are within cells. It's the mitochondria that stain red in the lab, (red oil 'o' stain ?) thereby giving "red fibers" their name.

From here:
http://www.isokinetics.net/advanced/musclefibertypes.htm

"It must be remembered that skeletal muscles, although a mixture, can only have one type of muscle fiber within a motor unit. "

I think you've used "muscle cell" once to mean "motor unit".


re: nerve cells and stem cell research. There's a difference between stem cells versus undifferentiated tissue cells. There is some evidence that adults may have a few stem cells, but it's weak and controversial. What is not controversial is that we have a lot of undifferentiated cells whose role is to act as points of origin for tissue regeneration. However, undifferentiated cells that can turn into nerve cells to repair damaged nerves are either rare or nonexistent. This is why a dead nerve does not regenerate the same way a dead blood vessel can. This type of damage is basically unfixable. The quest for stem cells is especially important to nerve-damaged patients for this reason.

Nerves do heal. Spinal nerves higher than the 'horses tail' in the low spine do not. Nerves further from the brain do. I've had both a median nerve and a digital nerve severed and repaired.

[blutoski]

What about red blood cells, that don't reproduce, but are made in bone marrow? What is the name for that type of reproduction?

You might be thinking about erythropoiesis. This starts with Mitosis.




Skin cells, muscle cells, and red blood cells each have a slightly different way of reproducing. I don't know the nomenclature. I'm better with concepts than names. (duh!) Skin, bone, and intestinal cells are constantly reproducing, without stem cells. They need to, they suffer constant wear. Red blod cells are produced by other cells, that are not red blood cells. Muscle cells come from a fixed source of stem cells, that will be differentiated into different types of muscle. I know that these different systems of production are important in biopsys, since the cellular genes are replicated from different pathways.

It's also why we have lots more cancers in skin, bone, and intestines than we do in muscles and nerves. I.E., those cells which are reproduced from other identical cells suffer more mutations. Those cells produced from a cloistered genetic source get fewer mutations, but are slower to be produced.

Basically, but it's still all mitosis, and secondly, these don't come from the same type of stem cells that are under research: they come from undifferentiated tissue cells known as 'adult stem cells'. The difference is that an undifferentiated tissue cell / adult stem cell has limited ability to differentiate. ie: a true stem cell can become any type of tissue, whereas an adult stem cell has already decided it will be 'some kind of' blood tissue.

In my research I deal with an intermediate type of cell called a 'progenitor cell', which is a sort of temporary adult stem cell that propagates a cell line. This has ramifications for immunity, as a white blood cell line can suddenly die out because its number of divisions has been completed, and the patient becomes vulnerable. (one healthfraud concern I have about this is that products that 'stimulate' the immune system can be argued to be wasting these scarce divisions)


re: cancer. Doubtful. Most of the tissues you mention are external, and they have a higher exposure to mutagens. An example of a cancer affecting a cell type that comes from a 'cloistered' source is leukemia, which is frustratingly common. Cancer has too many causes/triggers/&c to make a generalization like this. Endocrine triggers may play a much larger role than external mutagens, for example.





I think muscles have fibers, fibers have cells. Red Fibers have fat-burning cells, White fibers have sugar burners. Mitochindria are within cells. It's the mitochondria that stain red in the lab, (red oil 'o' stain ?) thereby giving "red fibers" their name.

From here:
http://www.isokinetics.net/advanced/musclefibertypes.htm

"It must be remembered that skeletal muscles, although a mixture, can only have one type of muscle fiber within a motor unit. "

I think you've used "muscle cell" once to mean "motor unit".

No, that's the secret: muscle cells are multinucleated, and can have multiple motor units along their lengths (motor units are defined as regions along the muscle fibre that share a triggering nerve). For all intents and purposes, a muscle cell is a muscle fibre, although this is not always the case.

re: mitochondria... all cells have mitochondria, but yes, red muscle fibres have larer mitochondria. However, what gives 'red' muscle (dark meat) its distinctive colour is that it also has a higher concentration of myoglobin. You don't need a stain: red muscle fibres really do look darker.




Nerves do heal. Spinal nerves higher than the 'horses tail' in the low spine do not. Nerves further from the brain do. I've had both a median nerve and a digital nerve severed and repaired.

I didn't say 'severed' - I said 'dead'. A dead nerve cannot regenerate, unlike a dead artery. Thus, the problem. Damaged nerve cells can regenerate. A dense neurological area like the brain or a remote ganglia can regenerate its function by recruiting redundant nerves to replace the dead ones. But this is not the same.

[Capsid]

Red blood cells divide by mitosis from stem cells in the bone marrow and then lose their nucleus and as a consequence can't divide any further Their division is no different than any other somatic cell.

Cell division is either by mitosis in somatic cells or meoisis in germ cells.

Mitochondria don't have a colour! They stain red because the stain is red they could equally stain orange or blue depending on the dye used. The red colour is due to the large number of capillaries containing red blood cells and as a result the muscle can sustain aerobic activity for prolonged periods (slow twitch).

So, there are slow twitch, type I (red muscle fibres) and fast twitch, type II (white muscle fibres).

[Pro7]

Red blood cells divide by mitosis from stem cells in the bone marrow and then lose their nucleus and as a consequence can't divide any further Their division is no different than any other somatic cell.

Cell division is either by mitosis in somatic cells or meoisis in germ cells.

Mitochondria don't have a colour! They stain red because the stain is red they could equally stain orange or blue depending on the dye used. The red colour is due to the large number of capillaries containing red blood cells and as a result the muscle can sustain aerobic activity for prolonged periods (slow twitch).

So, there are slow twitch, type I (red muscle fibres) and fast twitch, type II (white muscle fibres).

Wait a second. Im confused here.

Isnt Blood itself is BLUE? .. and it turns red when it touches oxygen. I.E. as in cutting yourself? :D

[Schneibster]

Wow, blutoski, you stimulate me to ask questions. I hope they are sensible.

My understanding of apoptosis is that it is a cancer defense mechanism. It fails in malignant cancers, and this is one of the reasons they kill- they multiply at the expense of surrounding body cells, taking nutrients and killing competing cells that are cooperating without cooperating themselves in the body's survival. Normally, such cells would be stimulated to "suicide" by the apoptosis mechanism, but in cancer that fails. Is that correct?

[Pro7]

Membranes are the first to go when a cell divides. It starts by stretching itself. Until finally at completion, the cell has completely divided, thus making it into a "clone copy" of itself.

This is what scientists need to study about. They need to study HOW to stop membranes from allowing such divisions. Once scientists do discover a way to stop divisions, then they will be able to apply it to cancer cells, to finally stop it.

I know it sounds farfetched, but at least a scientist with genetic -biology knowledge should be looking at that possibility.

[Capsid]

Wait a second. Im confused here.

Isnt Blood itself is BLUE? .. and it turns red when it touches oxygen. I.E. as in cutting yourself? :D
The blood is carrying oxygen to the muscles.

[casebro]

Okay, This discussion has promted me to google up "Myogenisis".

Good site: <http://classes.aces.uiuc.edu/AnSci312/Muscle/Musclect.HTM>

Lessee if I can cut and paste:

Take home messages

* No formation of new myofibers or cardiomyocytes after birth
* Myofibers and cardiomyocytes become larger; longer and wider after birth
* Myofibers and cardiomyocytes must maintain size of DNA
* Cardiomyocytes increase DNA content by karyokinesis
* There must be an increase in number of myonuclei (nuclei withing myofibers)
* However, the myonuclei of skeletal muscle fibers do not divide because they are in TD


So, basically, muscle cells do not divide, or multiple, after birth. They can subtract (die) and add, via the Myoblasts that were formed before birth. (Who said everything is math?) The Myoblasts link up and differentiate into red or white fibers. Skeletal muscle fibers must hypertrophy to add muscle bulk, after the Myoblasts are used up. The Heart's fibers do multi-nucleate via Karyokinesis (be careful in night clubs, use protection), but they don't divide into two cells, no Cytokenisis.

So, not so simple as "all cells reproduce by Mitosis".

[Pro7]

The blood is carrying oxygen to the muscles.

YEP. ;)

[Taffer]

http://en.wikipedia.org/wiki/Telomerase#Telomerase_as_a_potential_drug_target

Cancer is a very difficult disease to fight because the immune system cannot recognize it, and cancer cells are immortal; they will always continue dividing.

>Thats the first sentence indicated in that url. I strongly disagree that cancer cells are immortal.

Cancer cells are immortal, by the very definition of that term as applied to cellular biology. Cancer cells do not undergo programmed cell death.

This is my opinion:

All replicating cells use "membranic action" in order to divide and replicate. If scientists were to find a way to halt specific membranic action of cancer cells, then a solution would be developed. I really think that scientists are wasting their time experimenting on telomerase formulas.

The problem with this is, how do you expect to target only the cancer cells, and not everything else? Sure, it would stop cancer cells from dividing, but it would stop everything else too.

[Taffer]

Wow, blutoski, you stimulate me to ask questions. I hope they are sensible.

My understanding of apoptosis is that it is a cancer defense mechanism. It fails in malignant cancers, and this is one of the reasons they kill- they multiply at the expense of surrounding body cells, taking nutrients and killing competing cells that are cooperating without cooperating themselves in the body's survival. Normally, such cells would be stimulated to "suicide" by the apoptosis mechanism, but in cancer that fails. Is that correct?

Pretty much. One major cause of cancer cells is the failure of the gene p53, which initates DNA repair and apoptosis pathways in the presence of DNA damage. Some forms of inherited cancers (for example, inherited gastric cancer) are due to the family having a large proportion of non-functional p53 alleles.

ETA: IIRC, cells are actually going cancerous in you all the time, but are also undergoing apoptosis to prevent their own spread.

[Taffer]

Membranes are the first to go when a cell divides. It starts by stretching itself. Until finally at completion, the cell has completely divided, thus making it into a "clone copy" of itself.

What do you mean by "the first to go"? If you mean the first step, then you should look up mitosis. The cellular membrane doesn't so much stretch, though. The two daughter cells are each roughly half the volume of the parent cell. The wiki article on mitosis is quite good, I suggest you read it.

This is what scientists need to study about. They need to study HOW to stop membranes from allowing such divisions. Once scientists do discover a way to stop divisions, then they will be able to apply it to cancer cells, to finally stop it.

Again, how do you apply it only to the cancer cells? What if the cancer is diffuse? How do you target only the cancer cells, and not everything? The problem with cancer is that they are still your own cells. There is little to no difference between a cancer cell and a normal cell, except that a cancer cell is immortal (i.e. replicates endlessly without programmed cell death).

I know it sounds farfetched, but at least a scientist with genetic -biology knowledge should be looking at that possibility.

It is a good thought, but not one I can see put into practice. What would be a better solution would be the addition of vital apoptosis proteins which cancer cells lack, which would cause the cancer cells to die.

[blutoski]

Wow, blutoski, you stimulate me to ask questions. I hope they are sensible.

My understanding of apoptosis is that it is a cancer defense mechanism. It fails in malignant cancers, and this is one of the reasons they kill- they multiply at the expense of surrounding body cells, taking nutrients and killing competing cells that are cooperating without cooperating themselves in the body's survival. Normally, such cells would be stimulated to "suicide" by the apoptosis mechanism, but in cancer that fails. Is that correct?

Apoptosis is a generalized mechanism with many functions. In embryos, strategic apoptosis generates limbs and digits when cells die in strips so as to separate the living tissues.

As a defese, in principle, as soon as a cell detects malfunction, it is to destroy itself. But this fails often.





Membranes are the first to go when a cell divides. It starts by stretching itself. Until finally at completion, the cell has completely divided, thus making it into a "clone copy" of itself.

This is what scientists need to study about. They need to study HOW to stop membranes from allowing such divisions. Once scientists do discover a way to stop divisions, then they will be able to apply it to cancer cells, to finally stop it.

I know it sounds farfetched, but at least a scientist with genetic -biology knowledge should be looking at that possibility.

For at least a hundred years, actually. The trick is figuring out how to stop only the cancer cells from dividing. Then you've only postponed the problem: how do you kill them so you don't have to take the anti-division drug forever?

Colchecine is an example of a substance that has been explored quite exhaustively, and works through the mechanism you propose: it prevents cell division by botching the membrane's ability to pinch and cleave the mother cell into daughters. You end up with a cell filled with generations of chromosomes, which is useful in experiments, but not much else.

Taxol/Tamoxifen, sort of goes from the other angle, siezing up the spindle fibres and making cell division difficult.

There are dozens of other approaches, all with the same weakness: they are just as destructive to our healthy cells, and the patient's whole body is being exposed to the cell-division attack. This is the current state of surgery/chemo/radiation therapy today: how to get that very last cell without too much collateral damage.

My interest (I will be starting new research in September - fingers crossed) is to find ways to differentiate between rogue tumour cells and their healthy peers of the same cell type, and have them marked with antibodies for the immune system to take them out.

[blutoski]

Pretty much. One major cause of cancer cells is the failure of the gene p53, which initates DNA repair and apoptosis pathways in the presence of DNA damage. Some forms of inherited cancers (for example, inherited gastric cancer) are due to the family having a large proportion of non-functional p53 alleles.

ETA: IIRC, cells are actually going cancerous in you all the time, but are also undergoing apoptosis to prevent their own spread.

The major mechanism for destroying cancer cells or proto-cancerous cells is probably their own apoptosis.

The second most important mechanism is probably specific-immune targetting, known as "tumour surveillance".

The existence of tumour surveillance was long hypothesized, but only recently confirmed.

[The Mad Hatter]

It's been observed that genetic problems like Down's syndrome increase in frequency with the age of fathers, but not with age of mothers, so damage does seem to accumulate in the germline but it's different from somatic cell damage.

Actually, it's the other way around - it's the mother's age that affects the probability (exponentially, I think) of getting Down's syndrome. (Source (http://www.nichd.nih.gov/publications/pubs/downsyndrome.cfm#TheOccurrence)). Sorry for nitpicking, but I thought I should put my genetics classes to some use...

This makes more sense, because eggs are sort of "frozen" in development through most of a girl's life, and are therefore susceptible to some of the damage that affects somatic cells, which in turn causes your non-disjunction.

[Asolepius]

Actually, it's the other way around - it's the mother's age that affects the probability (exponentially, I think) of getting Down's syndrome. (Source (http://www.nichd.nih.gov/publications/pubs/downsyndrome.cfm#TheOccurrence)). Sorry for nitpicking, but I thought I should put my genetics classes to some use...

This makes more sense, because eggs are sort of "frozen" in development through most of a girl's life, and are therefore susceptible to some of the damage that affects somatic cells, which in turn causes your non-disjunction.No, not nitpicking at all - thanks for the correction:)

[RecoveringYuppy]

Wait a second. Im confused here.

Isnt Blood itself is BLUE? .. and it turns red when it touches oxygen. I.E. as in cutting yourself? :D
No, human blood is always red. It's a slightly different shade of red when oxygenated. It appears blue through your skin due to filtering of light going through your skin. Medical texts also differentiate between veins and arteries by depicting one in blue and one in red but that's just to make it easiere to tell which is which in the text.

[blutoski]

Apropos: A new look into cancer's roots - Scientists revive study of stem cells' link to cancer (http://www.baltimoresun.com/news/health/bal-te.stem19mar19,0,4234549.story)

[Thomas1016]

I cant post url's yet but if you will go to myspace and search dr. michio kaku he has a bbc video on is web page where he explaines in simple terms how close we are being able to stop ageing.

maybe someone else can post the url so it can be clicked on.

[blutoski]

Actually, it's the other way around - it's the mother's age that affects the probability (exponentially, I think) of getting Down's syndrome. (Source (http://www.nichd.nih.gov/publications/pubs/downsyndrome.cfm#TheOccurrence)). Sorry for nitpicking, but I thought I should put my genetics classes to some use...

This makes more sense, because eggs are sort of "frozen" in development through most of a girl's life, and are therefore susceptible to some of the damage that affects somatic cells, which in turn causes your non-disjunction.

The only quibble I have with this statement is that in the case of non-disjunction mutations, these actually took place during the formation of the egg cell, which IIRC happens when the woman is an embryo.

The theory is that the ovary somehow can tell which eggs are the most viable, and sends them out first.

[The Mad Hatter]

The only quibble I have with this statement is that in the case of non-disjunction mutations, these actually took place during the formation of the egg cell, which IIRC happens when the woman is an embryo.

The theory is that the ovary somehow can tell which eggs are the most viable, and sends them out first.

That's weird...I haven't heard that before. My genetics professor told us a week ago that the eggs are created without it, and that the eggs are affected while in "storage." For now, I'll have to stick to his explanation, since I'm being tested on it, but I'll look into yours. Do you have any articles or sources explaining it?

If the theory you mention is true, then that's damn cool.

[blutoski]

That's weird...I haven't heard that before. My genetics professor told us a week ago that the eggs are created without it, and that the eggs are affected while in "storage." For now, I'll have to stick to his explanation, since I'm being tested on it, but I'll look into yours. Do you have any articles or sources explaining it?

If the theory you mention is true, then that's damn cool.

It should be evident from examining the mechanism: "nondisjunction". This is a failure of chromosome separation. One chromosome stays joined to its equal, so the daughter cells are not even. In the case of Down Syndrome, it's Chromosome #21. One daughter cell has 22 chromosomes, the other has 24 (an extra #21).

When the 22-chromosome egg fuses with a sperm, making 45 chromosomes - it is not viable.

When the 24-chromosome egg fuses with a sperm, making 47 chromosomes (three #21 chromosomes) - a person with Down Syndrome is born.

Egg cells are all formed before birth. This original error has happened while 'mom' was an embryo.

There are, of course, other ways to get Down Syndrome, but this mechanism covers 96% of the incidences.

[The Mad Hatter]

It should be evident from examining the mechanism: "nondisjunction". This is a failure of chromosome separation. One chromosome stays joined to its equal, so the daughter cells are not even. In the case of Down Syndrome, it's Chromosome #21. One daughter cell has 22 chromosomes, the other has 24 (an extra #21).

When the 22-chromosome egg fuses with a sperm, making 45 chromosomes - it is not viable.

When the 24-chromosome egg fuses with a sperm, making 47 chromosomes (three #21 chromosomes) - a person with Down Syndrome is born.

Egg cells are all formed before birth. This original error has happened while 'mom' was an embryo.

There are, of course, other ways to get Down Syndrome, but this mechanism covers 96% of the incidences.

But egg cells are not formed before birth - they go through some of meiosis before birth, but remain in arrested development until puberty. One by one, they finish meiosis, and go through disjunction. Since the telomeres are slowly weakening throughout a girl's lifetime, non-disjunction becomes increasingly likely to occur in this stage.

Or at least I hope that's what happens, because that's what college students are being taught :rolleyes:

[Taffer]

But egg cells are not formed before birth - they go through some of meiosis before birth, but remain in arrested development until puberty. One by one, they finish meiosis, and go through disjunction. Since the telomeres are slowly weakening throughout a girl's lifetime, non-disjunction becomes increasingly likely to occur in this stage.

Or at least I hope that's what happens, because that's what college students are being taught :rolleyes:

You are correct.

At least, according to my human genetics course. :D