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- If stem cells divide all the time then why don't we often get a stem cell cancer?(7 votes)
- Stem cells have the ability to divide all the time, but their division and differentiation is kept under control by protein signals.(9 votes)
- If senescence is defined as the inability to undergo mitosis/replicate, and post-mitotic cells don't undergo that anyways, how can they become senescent? What is the difference between just senescence in general and replicative senescence? Do post-mitotic cells really get used throughout our lifespans, without replacement/repair (besides the special case of tissue specific stem cells)?(4 votes)
- So do HeLa cells simply have a high volume of telomerase, which allows them to divide (potentially) endlessly?(3 votes)
- A mutation in the HeLa cells causes them to express telomerase, which is not normal for somatic cells. Through repeated cell divisions, the telomeres erode, but the presence of telomerase (terminal transferase) allows the addition for the tandem repeats. As for the amount of telomerase produced, I would make an educated guess and say that HeLa cells wouldn't produce more telomerase than other cells (stem cells) that are supposed to express the gene for telomerase.
Hope this helps! :)(2 votes)
- At5:21in the video above, since the cell has stopped dividing, does the cell become a post mitotic cell?(2 votes)
- The Hayflick limit states that a cell can only divide so many times -- but how do we count how many times a given cell has divided? For example, a cell divides into two "new cells", so do we consider each of the "new cells" as already having divided once, or does their count restart? If the amount of times a cell divides is traced back to the original cell that divides, wouldn't all our cells reach the Hayflick limit at the same time since they all originated from the same cell?(2 votes)
- First note that the Hayflick limit is an observation based on studying a single cell type in culture. Thus, while it represents a valuable insight it is not a universal "law".
For typical mammalian cells the age is inherited from the mother cell — one clear exception to this is in the germ line. This aging seems to be associated with telomere shortening in vertebrates§.
However, there are also many examples of asymmetric mitotic divisions that appear to dump all the "bad" aging-associated factors into one daughter cell and thereby rejuvenate the other daughter. This "replicative rejuvenation" is known to happen in prokaryotes, yeast, and mammalian stem cells.
In addition, cells don't divide at the same rates, so even if the Hayflick limit was universally true not all cells would die at the same time.
Does that help?
§Note: For more about this subject:
- My understanding is that recent research (years after this video was made) is showing that telomere shortening doesn’t occur with every division or even every 100th division, but simply correlates with aging. With each division, telomerase may add a much longer sequence to compensate for a shorter telomere previously. The length varies from division to division, but they average out to maintain the same length.(2 votes)
- Why can't we "apply" telmorase to all our cells and live forever?(1 vote)
- In many mammals somatic cells telomeres tend to get shorter with each division. When they get short enough it seems that the cells will either senesce or die — this is theorized to act as a natural limit on the number of somatic cell divisions (known as the Hayflick limit).
While this limit constrains how long an organism can live, it also helps prevent cancerous cells from continuing to divide.
Thus, even if we found a safe way to add telomerase to all of our cells (very challenging) it might just result in our dying of cancer sooner than old age would have naturally killed us.
That being said, if we found a way to temporarily turn on telomerase and only in healthy tissues this could potentially be helpful.
Note, however, that this is an area of active research and we probably don't know enough yet to try telomere modification (though at least one person has supposedly tried this).
This wikipedia article on telomeres seems worth reading:
Does that help?
Relevant review articles:
- Why does the introduction of telomerase lead to an increased risk of cancer in mitotic cells when at the cells inception they divided at the same rate?(1 vote)
- It goes back to very reason why cells reach senescence in the first place. I may be going off on a limb, but I think the collective effort of cells going through senescence is an evolutionary advantage to avoiding tumor growth. Maybe senescent cells' DNA repair mechanisms are getting old and inefficient. So when you introduce telomerase to a cell that was meant to be senescent, yes, you could keep replicating, but the DNA repair mechanisms are not so great that you could have a higher chance of developing cancer.(2 votes)
- How does a cell know whether it is senescent or not? (i.e. how does it know that the telomeres are depleted?) Are there certain chemicals that are released when the ends of the DNA (without telomeres) are exposed?(1 vote)
- "There is accumulating evidence that when only a few telomeres are short, they form end-associations, leading to a DNA damage signal resulting in replicative senescence (a cellular growth arrest, also called the M1 stage). "
Jerry W. Shay and Woodring E. Wright
Senescence and immortalization: role of telomeres and telomerase
Carcinogenesis (May 2005) 26 (5): 867-874 first published online October 7, 2004 doi:10.1093/carcin/bgh296
- @2:15, why is it that embryonic stem cells do not face the same DNA degradation faced by mitotic cells? Do they not undergo the same process of DNA replication with the same machinery as mitotic cells?(1 vote)
- They have telomerase to rebuild the telomeres. This way the stem cells do not go into important gene loss. Somatic cells do not have the telomerase and so they lose the telomeres which eventually causes them to reach senescence.(2 votes)
- So, in your body you have a few different overarching types of cells. You've got, for one you've got your cells that are actively able to divide. Some examples would the epithelial cells that make up your skin. And you've got your fibroblast cells that make up the scaffolding of most of your organs. Like, say you kidneys and your liver. And even the endothelial cells that line the insides of your blood vessels. So, these cells, right, and their precursors, they can all divided by mitosis, and that's to help replenish and regenerate the tissues that they're a part of, right? And actually, we'll include some of our stem cells in here tool. The cells that these other initially come from. I will call this whole set of cells here mitotic cells. They undergo mitosis. So, we also have another group of cells in our bodies that we refer to as non-mitotic cells, or actually post mitotic cells. That's the most, that's a more accepted name, and you can probably guess why. They don't undergo mitosis. They're incapable of proliferation. And you might sensibly be thinking that, "Well, hey, that means that they can't "repair and regenerate like our mitotic cells over here." And you'd be on the right track. They certainly have a limited ability to repair or regenerate the tissues that they're a part of. And sorry, some examples would be, say, neurons either within the brain or elsewhere in your nervous system. And heart muscle cells, right, these are neurons and heart muscle cells. These are both examples of post-mitotic cells. But yeah, you're on the right track. The, this tissue doesn't regenerate by mitosis of these cells like what happens over on this side here. This tissue over here regenerates only very slowly and only by asking some special tissue-specific stem cells to help them out. But it's a slow, slow process of repair in post mitotic tissue so to speak. So, here's the thing, though. Here's the problem with mitotic division So, what the cells on this side do. So, with mitosis comes DNA replication because in order to create new daughter cells you have to copy your DNA to pass on, right? But DNA replication in basically every mitotic cell besides our embryonic stem cells has this interesting little caveat. So, let me show you what I mean here. So, here's our cell ready to start mitosis, right? So, it wants to copy its DNA to pass a full set onto each of its daughter cells. So, here's our DNA. Remember in eukaryotes like us humans we have nice linear strands of DNA, and we have lots of them as opposed to our prokaryotic bacteria friends who have circular DNA. So, here's our linear DNA and actually at the ends of our DNA strands, right, on both sides we have these little caps. Sorta like the little plastic tips on the ends of your shoelaces and just like how the little plastic tips protect your showlaces from fraying or getting worn out, our little telomeres, that's what these tips are called, our telomeres prevent damage from happening to our DNA during the copying process. So, to clarify these telomeres at the ends here don't actually code for any proteins. They don't have any genes on them. All the important DNA's in this section here, this middle, I guess, middle section. So, I said that there's potential DNA damage during the copying process. What'd I mean by that? Well, the machinery that copies our DNA, our DNA preliminary system. It kinda works in a funny way. It doesn't actually copy our DNA all the way to the end. So, what we see is that each time DNA is copied you lose a little bit of telomere here. So, every time the DNA gets copied you lose a little bit more, and a little bit more, and a little more of the end. So, lucky for us instead of having really, really important coding DNA at the end of our chromosomes. We've got our telomeres. So, again, it's the telomeres that end up becoming slightly shorter at the end of each DNA replication cycle. And it turns out that a cell can undergo about 60 or 70 or so cell divisions before the telomeres get too short, and then all this important coding DNA here starts to become at risk of damage from further replications. But not to worry. We have a contingency plan built in so once the telomeres get too short the cell initiates a DNA damage response. So, it sort of rings these internal alarm bells. And it sort of gives up its ability to divide because it really wants to prevent any more shortening of this chromosome that would happen in further rounds of replication, right? So, it loses its ability to divide and by doing that it has become what's called a senescent cell. And before I explain what exactly that is there's just two things I want to point out about this. So, the first thing is that if a cell reaches senescence because its telomeres have become too short we say it's reach replicative senescence and the second thing is that the number of times a cell can divide before reaching senescence, replicative senescence, is called its Hayflick limit and that's named after the scientist who figured that out. And again, it's generally around about 60 or so divisions. So, now that we've gotten all of that out of the way what exactly is senescence? Well, basically it's a change in a cell's state from a happy, active mitotic cell, right, IE one that divides on a regular basis to one that's nondividing, and possibly less happy. I'll have to ask a senescent cell how it's feeling one of these days. But it undergoes all of these other changes as well like it starts expressing all sorts of genes that it didn't before, and it starts to look a little bit different, and it starts to respond a bit differently to the cells around it. But the important thing is that while it's still contributing to the structure of your body it's stilling hanging around in your tissues, it's not allowed to replicate anymore. And kinda the key with all roads to cellular senescence, be it through reaching your Hayflick limit as we just saw or through other ways which I'll mention in a second. The key is that cells transform into a senescent state to prevent impending DNA damage from happening and causing, maybe cancer, a tumor, possibly being passed on to daughter cells. So, the cells ability to divide gets turned off. And other causes appear. Well, essentially anything that threatens the integrity of your DNA. So, maybe if you had telomeres that just don't work properly or maybe you sustained some DNA damage through a mutation of some type, or maybe some toxin damage to your DNA. Any of these could really just as easily result in your cell becoming senescent, non-dividing. So, is there actually a problem with senescent cells? Are we happy about them? Are we upset with them? What's the deal here? Well, we're not really sure yet but conceptually an easy way I like to think about them is that, well, on one hand they help prevent tumors or cancers from happening because they're not allowed to divide anymore. But on the other hand as we get older and our tissues have more and more senescent cells in them the tissue can't really repair itself as well as it used to because there's fewer actively mitosing cells around, right? And there's actually also some evidence linking senescent cells to age-related diseases like cataracts. But this is a pretty active area of research. So, for now we'll just have to keep an eye on these cells to see what new research comes up with for us. Now, let me zoom out a bit here to show you something else. So, here's our mitotic cells, right, that by definition are the only ones that can undergo replicative senescence. And over here are our post mitotic cells and these guys can't reach replicative senescence, right, because they don't replicate but they can be induced to become senescent if their DNA's at risk of becoming damaged in basically just the same way as I mentioned earlier on DNA damage from some source. And the last thing I just wanna draw out a graph here to represent our different types of cells and their tendencies with division. I think this will really help us to get the picture here. So, here's our graph. Here's our Y axis here, and here's our X axis. And on the Y axis I wanna put cell division capacity. Okay, so, capacity of this cell to divide and on the X axis here I'll put number of doublings which is essentially how many times a cell as divided already. And this will all sort of make sense in a second here. So, our somatic cells, our regular body cells, that are able to mitose, to undergo mitosis, they start out, say, up here, right, with a pretty high cell division capacity. They're able to divide a lot. And as they continue to divide, and divide, and divide they sort of move this way. Their curve sort of curves down this way as the number of doublings that they have done increases, right? So, you can see the more doublings they've done the lesser their cell division capacity, right? And that's because their telomeres, with each doubling, their telomeres are getting shorter. So, their capacity to divide is getting lower with the increased number of doublings, okay? But we have another type of call, right? We have, say, some of our stem cells, they start off up here, right? Let's say they start off at the same place. They have a really high cell division capacity but as they divide, right, their line, their curve, just stays really high, right? Their cell division capacity regardless of the number of doublings, regardless of the number of times they've divided their cell division capacity stays really high, right? So, why would that be? Why might that be? Why would they be so different from our somatic cells? Well, it turns out that they express a special enzyme called Telomerase. And what Telomerase does is it, every time one of these cells from our stem cell curve here, every time it undergoes replication and loses a bit of telomere. Telomerase the enzyme sort of springs into action and adds back that little bit of telomere, right? So, that means that these cells are never gonna reach a Hayflick limit, right? They're just gonna have the ability to replicate as many times as they want. And that's because they express Telomerase. And the very last thing I'll say is that sometimes your somatic cells, right, they can develop a mutation in their DNA that causes them to start expressing Telomerase. So, now they have the enzyme Telomerase present within the cell, right? So, now they jump off our curve here, our regular somatic cell curve here, because they get the ability to replicate as many times as they want. They essentially escape senescence and this is one of the ways that cancer occurs because now you have a group of cells that can go on and multiply out of control, and form a tumor.