Reproduction vs aging damage
aikikai 01 Nov 2008
I have been wondering for a while about human creating offsprings and aging damage. Here it is how it goes:
We assume that aging is the cause of damage on the bodies cells and DNA. This means that eventually you will have damage on "all" your cells in your body after a time period (aging).
Then if so, how come that we can after millions of years, generation after generation reproduce and create healthy offspring? The female egg and the mans sperm would have a lot of damage. This would in theory mean that we would create offspring that is already aged. But that reality isn't so.
So, what I know is that the sperms and eggs are fresh and "free" from DNA damage, so we can create healthy offspring. Then why is the reproduction material sperms and eggs free from aging damage, if the aging theory is mainly about wear and tear?
This must mean that we have two scenarios; either we have incredible mechanisms of reparing and protecting sperms and eggs from aging damage, or that the aging theory about wear and tear is not completely true. If your body can repair eggs and sperms, why canät it repair other damage?
I know that there is risks of getting sick offspring if you get children at an older stage in your life, but that seems to be minimal.
I hope someone knows what I am talking about and has any information regarding this.
Edited by aikikai, 01 November 2008 - 01:14 PM.
maestro949 01 Nov 2008
Hi,
I have been wondering for a while about human creating offsprings and aging damage. Here it is how it goes:
We assume that aging is the cause of damage on the bodies cells and DNA. This means that eventually you will have damage on "all" your cells in your body after a time period (aging).
Then if so, how come that we can after millions of years, generation after generation reproduce and create healthy offspring? The female egg and the mans sperm would have a lot of damage. This would in theory mean that we would create offspring that is already aged. But that reality isn't so.
So, what I know is that the sperms and eggs are fresh and "free" from DNA damage, so we can create healthy offspring. Then why is the reproduction material sperms and eggs free from aging damage, if the aging theory is mainly about wear and tear?
This must mean that we have two scenarios; either we have incredible mechanisms of reparing and protecting sperms and eggs from aging damage, or that the aging theory about wear and tear is not completely true. If your body can repair eggs and sperms, why canät it repair other damage?
I know that there is risks of getting sick offspring if you get children at an older stage in your life, but that seems to be minimal.
I hope someone knows what I am talking about and has any information regarding this.
Think of somatic cells as a damage sponge simply sacrificed to protect the truly immortal germline cells from the environment. When they are differentiated into their functional cell types (liver, heart, muscle, neurons) they typically lose some of the protective properties that are afforded to germline cells. They also are more exposed to a much harsher environment and are working harder to carry out their function.
Unfortunately, what you think of as you, is all somatic cells simply trying to protect the germline within egg and sperm, which in essense, are simply waiting around for a booty call.
Edited by maestro949, 01 November 2008 - 01:42 PM.
brokenportal 01 Nov 2008
aikikai 01 Nov 2008
Think of somatic cells as a damage sponge simply sacrificed to protect the truly immortal germline cells from the environment. When they are differentiated into their functional cell types (liver, heart, muscle, neurons) they typically lose some of the protective properties that are afforded to germline cells. They also are more exposed to a much harsher environment and are working harder to carry out their function.
Unfortunately, what you think of as you, is all somatic cells simply trying to protect the germline within egg and sperm, which in essense, are simply waiting around for a booty call.
It is still a riddle for me. Eggs and sperms can't escape from free radicals.
If these protective properties seems to withstand damage, then wouldn't there be a key there to develop therapies with the same protective properties for the rest of the body?
maestro949 02 Nov 2008
It is still a riddle for me. Eggs and sperms can't escape from free radicals.
Germline cells show similar immortal properties to that of embryonic stem cells. Those that are damaged self destruct and are replaced by Germline Stem Cells (GSCs). Imagine the evolutionary pressures to keep spermatogenesis optimized compared to that of the rest of the soma.
If these protective properties seems to withstand damage, then wouldn't there be a key there to develop therapies with the same protective properties for the rest of the body?
That's probably the most difficult of all anti-aging strategies as it means re-engineering many somatic cell lines and then displacing the existing cells within the cell populations. One sub-concept within this area that may have viable short-term possibility is finding the regulatory triggers that stimulate the stem-cell replacement process to be more effective. Other shorter-term strategies are to look for ways to make a series of small tweaks to slow, stop or reverse and or fix the damage.
brokenportal 02 Nov 2008
Germline cells show similar immortal properties to that of embryonic stem cells. Those that are damaged self destruct and are replaced by Germline Stem Cells (GSCs). Imagine the evolutionary pressures to keep spermatogenesis optimized compared to that of the rest of the soma.
Do you or anybody around here know what causes a stem cell to have immortal properties?
That's probably the most difficult of all anti-aging strategies as it means re-engineering many somatic cell lines and then displacing the existing cells within the cell populations. One sub-concept within this area that may have viable short-term possibility is finding the regulatory triggers that stimulate the stem-cell replacement process to be more effective.
Why cant stem cells be delivered with a few engineering tweaks right now to refresh tissue all over your body via the lymph system? Im not saying it can be done, I know little about it, Im just wondering, on the surface it looks good.
Other shorter-term strategies are to look for ways to make a series of small tweaks to slow, stop or reverse and or fix the damage.
You mean sens right?
maestro949 02 Nov 2008
Do you or anybody around here know what causes a stem cell to have immortal properties?
Someone else may be able to summarize better but as I understand it, spermatagonial and embryonic stem cells (these are the ones that don't seem to age whereas other types do) function in a highly specialized regulatory niche of gene expression that is geared towards symmetric cell division where the two new cells are (nearly) perfect copies of each other. Most downstream cell types lack this property as it's undesirable. Instead, these downstream somatic cells have, as part of their developmental process, signaling machinery for slowing and halting cell division to prevent runaway growth of the organ systems and organism as a whole.
Why cant stem cells be delivered with a few engineering tweaks right now to refresh tissue all over your body via the lymph system? Im not saying it can be done, I know little about it, Im just wondering, on the surface it looks good.
I'm not sure about the lymph system as a delivery channel but there is quite a bit of active research in learning what the exact signaling cascades are that manage the various types of stem cells and their activity. Combining gene therapy with stem cell therapy is probably our best short-term (1-3 decade) aging intervention IMO.
Other shorter-term strategies are to look for ways to make a series of small tweaks to slow, stop or reverse and or fix the damage.
You mean sens right?
Yes and No. SENS proposes a strategy that deals with certain aspects of the latter, i.e. fixing downstream damage that is a result of metabolism. SENS is critical of research attempts to slow or halt the damage accumulation via alterations to the upstream regulatory machinery as it is deemed as too complex. I see both sets of research as critical to the short and long-term success of anti-aging therapies.
Michael 05 Nov 2008
The first part of the answer was already given by Maestro949. Think of it in these broader terms. All organisms suffer aging damage to their molecular and cellular structures, yet the rate of aging varies from one species to the next, because natural selection has created conditions that select for different levels of investment into mechanisms to prevent and repair that damage. The amount invested in these mechanisms (and thus diverted away from other, also-crucial priorities, like fast growth, sharper claws, greater sprinting speed, etc) is determined by natural selection.We assume that aging is the cause of damage on the bodies cells and DNA. This means that eventually you will have damage on "all" your cells in your body after a time period (aging).
Then if so, how come that we can after millions of years, generation after generation reproduce and create healthy offspring? The female egg and the mans sperm would have a lot of damage. This would in theory mean that we would create offspring that is already aged. But that reality isn't so.
So, what I know is that the sperms and eggs are fresh and "free" from DNA damage, so we can create healthy offspring. Then why is the reproduction material sperms and eggs free from aging damage, if the aging theory is mainly about wear and tear?
But natural selection does not optimize for traits that benefit the health of the individual organism, but for fitness -- for traits that increase the ability to leave behind offspring that are, themselves, viable. How much fitness is conferred by more robust defenses against aging damage for a particular organism living in a particular niche depends on how many more viable offspring giving better defenses will confer, granted all the other things that threaten to kill the animal no matter what its rate of aging, granted its niche. So for instance flying rodents (bats, flying foxes) age more slowly than scurrying ones (mice and rats), because the former find it easier to escape predators, and thus investments in more robust anti-aging machinery pay off in additional viable young, because they don't get killed off before that extra potential for youth (including youthful reproduction) ever comes onto the scene.
So the first part of the answer is that, to the extent that sperm and egg DNA may be better protected against aging damage than the rest of the organism, that's because mutations that have led to such additional protections have paid off in past evolutionary time, for exactly the reason that you mention:we wouldn't be able to reproduce if our gametes' DNA weren't kept in very 'clean' shape.
The second part of the answer is that the 'lifestyle' of the egg in particular to some extent reduces its exposure to aging damage by default, because they spend most of their time in a deeply quiescent metabolic state (thus being exposed to fewer free radicals and other damaging agents caused by metabolism) and don't themselves divide for much of the time that the rest of the body is aging (unrepaired errors in DNA replication in preparation for cell division are the main cause of mutations, not attack by intrinsic or extrinsic damaging molecules).
But the third part of the answer is that the question itself is to some extent of the 'have you stopped beating your wife yet?' sort -- ie, there's a false premise buried in the question (since (I generously assume) you actually didn't beat your wife in the first place). In fact, sperm and egg DNA (not to mention their cellular structures) do suffer quite a bit of aging damage, which is part of the reason why older parents are less fertile (the sperm and eggs or their DNA are duds), have more miscarriages (in addition to problems in the ability of older mothers' bodies to support the developing fetus, the fetus itself is more likely to have fatal flaws), and are more at risk for birth defects (because of mutations in the egg and sperm DNA):
Birth Defects Genetics Center
PRECONCEPTIONAL COUNSELING
Virginia P. Johnson, M.D. c2000
Advanced maternal age is an indication for amniocentesis because of the risk of Down syndrome and other chromosomal disorders. In females, eggs are present at five months in utero. At birth there are four million eggs frozen in the dictyotene phase of meiosis 1, and after fertilization, these complete meiosis 2. A baby born to a 40-year-old woman literally comes from a 40-year-old egg, which then would have been exposed to environmental agents that can cause nondisjunction or failure of normal separation of chromosomes. This leads to aneuploidy, the most common of which is trisomy 21 [Down syndrome. Note that this is only one of several reasons for the increase in Down syndrome risk in older mothers, whose relative contribution is still undertain -MR]. Advanced paternal age also has an adverse effect. Mutations in a spermatogonium are replicated and passed to spermatocytes. Mutations associated with advanced paternal age include achondroplasia, Apert syndrome, neurofibromatosis, hemophilia, Marfan syndrome, Treacher-Collins syndrome, Waardenburg syndrome, thanatophoric dysplasia, and osteogenesis imperfecta; these are autosomal dominant traits. Examples of X-linked traits, for which a paternal age effect has been implicated include fragile X, hemophilia A (factor VIII), hemophilia B (factor IX), Duchenne muscular dystrophy, incontinentia pigmenti, Hunter syndrome, Burton agammaglobulinemia and retinitis pigmentosa.
Also in this area, it's worth noting that a lot of the reason why eggs are statistically in unexpectedly good shape when they are called to duty is not that they are better maintained, but that they are selected out: the woman's body destroys many defective eggs, to avoid wasting a reproductive opportunity by backing a flawed horse.
-Michael
brokenportal 05 Nov 2008
Unless maybe besides keeping the egg super in tact, this robust state of affairs might also be able to repair all forms of small amounts of aging damage?
What can we say for sperm though? They are constantly dividing, and so arent these eggs being given half copies of dna that are continuously in a down ward spiral of accumulated aging damage?
kismet 07 Dec 2008
caston 07 Dec 2008
And of course there would be some changes that would result in variation amongst people hence part of why we are all unique. There would also be unnoticeable changes to mechanisms of protein folding and even slight changes to prions that make up the zygot. Any change many actually result in random evolutionary change which might not be noticeable until a few generation down the line.
Also when you make a zygot your starting a new person from scratch. The cells will far more closely resemble the original zygot in terms of epi-gentic regulation. In a aging organism the cells will have changed a lot increaseing the overall complexity and making it harder for all the cells to work together.
It's also kind if like your windows installation slows down the registry and file system fill with crudd and accumulates junk and disorder. The body actually slowly shuts itself down when a lot of epigenetic disregulation occurs so a lot of aging is actually a graceful shutdown rather than just utter damage.
A new organism also has far less to worry about in terms of cancer as it still has very good epi-genetic regulation and no environmental damage to the soma for example UV rays.
Edited by caston, 07 December 2008 - 03:35 AM.
brokenportal 04 Mar 2009
Alright so then all these eggs are developed early on and heavily protected. But between the time the egg starts to divide until the time, whatever time that is, that the life time supply of eggs develops, a few miscues and free radicals sneak in there to age the eggs right? So after thousands of years of this how come we dont all have downs syndrome and achondroplasia and neurofibrosis and all the rest?
Unless maybe besides keeping the egg super in tact, this robust state of affairs might also be able to repair all forms of small amounts of aging damage?
What can we say for sperm though? They are constantly dividing, and so arent these eggs being given half copies of dna that are continuously in a down ward spiral of accumulated aging damage?
In addition to this, maybe its not that they can repair small amounts of damage, but that their programming doesnt allow for any?
VidX 05 Mar 2009
In addition to this, maybe its not that they can repair small amounts of damage, but that their programming doesnt allow for any?
Well if they experience some damage it means that's probably not the case.. It's actually hard to imagine a biological system (which in some sense is information, being copied, over and over) that avoids an entropy entirely (though - what's interesting - life seems to be a "structure" going towards extropy, while the whole universe is vice versa).
AgeVivo 05 Mar 2009
I read that Dolly was an exception. Isn't the new intra&extra cellular environment in which the nucleus is put responsible for an age "reset", as long as the DNA is approx OK ?
Prometheus 05 Mar 2009
Yes, epigenetic (DNA methylation and chromatin modification) changes in the DNA, enable the on/off status of genes to become the same as that in an embryonic cell. Provided the DNA sequence itself is not irreversibly damaged, you can, in principle, take a senescent cell and turn it into an embryo. Remarkable.What about cloning? Why aren't clones older than normal?
I read that Dolly was an exception. Isn't the new intra&extra cellular environment in which the nucleus is put responsible for an age "reset", as long as the DNA is approx OK ?
tst 13 Oct 2010
The first part of the answer was already given by Maestro949. Think of it in these broader terms. All organisms suffer aging damage to their molecular and cellular structures, yet the rate of aging varies from one species to the next, because natural selection has created conditions that select for different levels of investment into mechanisms to prevent and repair that damage. The amount invested in these mechanisms (and thus diverted away from other, also-crucial priorities, like fast growth, sharper claws, greater sprinting speed, etc) is determined by natural selection.We assume that aging is the cause of damage on the bodies cells and DNA. This means that eventually you will have damage on "all" your cells in your body after a time period (aging).
Then if so, how come that we can after millions of years, generation after generation reproduce and create healthy offspring? The female egg and the mans sperm would have a lot of damage. This would in theory mean that we would create offspring that is already aged. But that reality isn't so.
So, what I know is that the sperms and eggs are fresh and "free" from DNA damage, so we can create healthy offspring. Then why is the reproduction material sperms and eggs free from aging damage, if the aging theory is mainly about wear and tear?
But natural selection does not optimize for traits that benefit the health of the individual organism, but for fitness -- for traits that increase the ability to leave behind offspring that are, themselves, viable. How much fitness is conferred by more robust defenses against aging damage for a particular organism living in a particular niche depends on how many more viable offspring giving better defenses will confer, granted all the other things that threaten to kill the animal no matter what its rate of aging, granted its niche. So for instance flying rodents (bats, flying foxes) age more slowly than scurrying ones (mice and rats), because the former find it easier to escape predators, and thus investments in more robust anti-aging machinery pay off in additional viable young, because they don't get killed off before that extra potential for youth (including youthful reproduction) ever comes onto the scene.
So the first part of the answer is that, to the extent that sperm and egg DNA may be better protected against aging damage than the rest of the organism, that's because mutations that have led to such additional protections have paid off in past evolutionary time, for exactly the reason that you mention:we wouldn't be able to reproduce if our gametes' DNA weren't kept in very 'clean' shape.
The second part of the answer is that the 'lifestyle' of the egg in particular to some extent reduces its exposure to aging damage by default, because they spend most of their time in a deeply quiescent metabolic state (thus being exposed to fewer free radicals and other damaging agents caused by metabolism) and don't themselves divide for much of the time that the rest of the body is aging (unrepaired errors in DNA replication in preparation for cell division are the main cause of mutations, not attack by intrinsic or extrinsic damaging molecules).
But the third part of the answer is that the question itself is to some extent of the 'have you stopped beating your wife yet?' sort -- ie, there's a false premise buried in the question (since (I generously assume) you actually didn't beat your wife in the first place). In fact, sperm and egg DNA (not to mention their cellular structures) do suffer quite a bit of aging damage, which is part of the reason why older parents are less fertile (the sperm and eggs or their DNA are duds), have more miscarriages (in addition to problems in the ability of older mothers' bodies to support the developing fetus, the fetus itself is more likely to have fatal flaws), and are more at risk for birth defects (because of mutations in the egg and sperm DNA):Birth Defects Genetics Center
PRECONCEPTIONAL COUNSELING
Virginia P. Johnson, M.D. c2000
Advanced maternal age is an indication for amniocentesis because of the risk of Down syndrome and other chromosomal disorders. In females, eggs are present at five months in utero. At birth there are four million eggs frozen in the dictyotene phase of meiosis 1, and after fertilization, these complete meiosis 2. A baby born to a 40-year-old woman literally comes from a 40-year-old egg, which then would have been exposed to environmental agents that can cause nondisjunction or failure of normal separation of chromosomes. This leads to aneuploidy, the most common of which is trisomy 21 [Down syndrome. Note that this is only one of several reasons for the increase in Down syndrome risk in older mothers, whose relative contribution is still undertain -MR]. Advanced paternal age also has an adverse effect. Mutations in a spermatogonium are replicated and passed to spermatocytes. Mutations associated with advanced paternal age include achondroplasia, Apert syndrome, neurofibromatosis, hemophilia, Marfan syndrome, Treacher-Collins syndrome, Waardenburg syndrome, thanatophoric dysplasia, and osteogenesis imperfecta; these are autosomal dominant traits. Examples of X-linked traits, for which a paternal age effect has been implicated include fragile X, hemophilia A (factor VIII), hemophilia B (factor IX), Duchenne muscular dystrophy, incontinentia pigmenti, Hunter syndrome, Burton agammaglobulinemia and retinitis pigmentosa.
Also in this area, it's worth noting that a lot of the reason why eggs are statistically in unexpectedly good shape when they are called to duty is not that they are better maintained, but that they are selected out: the woman's body destroys many defective eggs, to avoid wasting a reproductive opportunity by backing a flawed horse.
-Michael
Good points. Does anyone have additional resources besides this, wiki doesn't go into much detail either.
Still, if you take these damaging influences into account, the offspring doesn't exhibit senility, albeit pathology. So i guess the main player here is telomerase and
Natural selection. You develop such a disease, you die, you do not reproduce. Favourable or neutral mutations can accumulate, though, they do so very slowly. I guess.
Further,
Is this a sustainable approach? (venter)Yes, epigenetic (DNA methylation and chromatin modification) changes in the DNA, enable the on/off status of genes to become the same as that in an embryonic cell. Provided the DNA sequence itself is not irreversibly damaged, you can, in principle, take a senescent cell and turn it into an embryo. Remarkable.What about cloning? Why aren't clones older than normal?
I read that Dolly was an exception. Isn't the new intra&extra cellular environment in which the nucleus is put responsible for an age "reset", as long as the DNA is approx OK ?
Is there such a mechanism?I'm not sure if this has been covered, but genetic recombination would be a large part of it. Obviously the sperm fuses with the embryo in utero and if some genes are damaged then they can probably replace them with good copies from the other.
In addition to this, maybe its not that they can repair small amounts of damage, but that their programming doesnt allow for any?
Well if they experience some damage it means that's probably not the case.. It's actually hard to imagine a biological system (which in some sense is information, being copied, over and over) that avoids an entropy entirely (though - what's interesting - life seems to be a "structure" going towards extropy, while the whole universe is vice versa).
Extropy, that's the keyword. Reminds me of the millenia-old self-repairing machines in in Clarke's The City and the Stars.
PWAIN 13 Oct 2010
.....The reason that the germ line does not die out in a catastrophe of errors has to do, on the one hand, with it's highly sophisticated mechanisms for cellular self maintenance and repairs and, on the other hand, with it's ability to get rid of it's more serious mistakes through continual rounds of competition. Sperm are produced in vast excess; usually only a good one can fertilize an egg. Egg-forming cells are produced in much greater numbers than can ovulate; stringent quality control eliminates the ones that fail to make the grade. And finally, if errors slip past all these checks, natural selection provides the final arbiter of which individuals are the fittest to transmit their germ line to future generations......
Cameron 17 Oct 2010
One very good question is what the heck is going on in neurons. The metabolic rate of neurons is extremely high, it is also said to be similar in humans to that of rodents' neurons, most of that metabolism is going towards signaling function. Now they're non-dividing cells, yet can last exponentially longer in humans, that is for more than 120 years. Now I don't know if the metabolic rate is similar for whale neurons, but if it is those are rumored to exceed 200 years of functioning in some whale species.Ive been wondering this same thing. Ive heard a few things about it but still dont fully understand. For example, when your non germ cells reproduce they accumulate the 7 diseases of SENS, the germ cells do too right? So why now after 30 or so years arent gametes producing offspring with X amount of damage accumulated in their stem cell pool, who then grow and produce offspring with X plus X amount of accumulated damage and so on?
As for the original question it is true that given the imperfect replication and repair all genetic information is being slowly corrupted, even the immortal germline and even unicellular lines. Probably due to the low-rate of corruption many viable copies can be created with minimal defects, and this pool can be replenished faster than copies become unviable.
There are species even multicellular ones that are said to reproduce clonally. So the clones are young.What about cloning? Why aren't clones older than normal?
Edited by Cameron, 17 October 2010 - 01:21 PM.
okok 17 Oct 2010
The germ line is also subject to change, but it's called mutation, and its ex- not entropic.
Maybe the ontogenetic forte could be engineered to aid the dominant somatic repair paradigm. Improved apoptosis/stem cells?
And how about cross-cell error correction? Think about the redundancy of all the cells in a body's specific tissue.
Cameron 17 Oct 2010
The germ line is also subject to change, but it's called mutation, and its ex- not entropic.
It has to have entropic components too, but in general as others have said bad copies are weeded out at various levels*(gamete competition, requirement for correct embryological development, functioning in the environment, etc). That does not change the fact that since errors from repair and replication are not negligible, any one cell's genetic information must be subject to slow corruption in the long run.
Using dvds is a good analogy, I think. If we think of it like dvds, and there was only a single master, barring extremely advanced error correction that makes error accumulation negligible, the master will eventually not be able to create viable copies. Thankfully we can use the copies to make more copies, but each and every single copy will be degrading too and should eventually lose the ability to make viable copies from it(but before it loses the ability it has already made enough viable copies to more than make up for its loss.).
nowayout 18 Oct 2010
In fact, it is amusing to think that we are in fact nothing but run-down less-successful descendents of our bacteria-like single celled ancestors. The most successful living cells on the planet are still the prokaryotes, who outnumber us vastly in number of individuals and in biomass. Replication errors made us much less adaptable and less successful than our single celled cousins (who are, by the way, effectively immortal).
Edited by viveutvivas, 18 October 2010 - 12:37 AM.
Arcanyn 23 Nov 2010
So, in summary, while in the case of our somatic cells, there is no mechanism to favour the proliferation of cells with beneficial (to the organism) and kill cells with deleterious mutations, resulting in an accumulation of deleterious ones, the same is not true when we go from one generation to the next - embryos with particularly deleterious mutations will not survive (whereas somatic cells with the same mutations could), and those with beneficial ones will be more likely to survive. As such, mostly good or neutral changes will be transmitted from one generation to the next.
Cameron 01 Dec 2010
So, in summary, while in the case of our somatic cells, there is no mechanism to favour the proliferation of cells with beneficial (to the organism) and kill cells with deleterious mutations, resulting in an accumulation of deleterious ones, the same is not true when we go from one generation to the next - embryos with particularly deleterious mutations will not survive (whereas somatic cells with the same mutations could), and those with beneficial ones will be more likely to survive. As such, mostly good or neutral changes will be transmitted from one generation to the next.
The mechanics of apoptosis allow for a system able to destruct some of the cells that have become defective, up to a point. The immune system can also attack some of the cells that have escaped control checks and endanger the organism. The negligible senescence organisms and organisms with ridiculous cell numbers(e.g. whales) must have systems for dealing with inevitable defects and for replenishing their tissues.
AgeVivo 01 Dec 2010
.
whales have few cells? interestingorganisms with ridiculous cell numbers(e.g. whales)
Edited by AgeVivo, 01 December 2010 - 11:03 PM.
Cameron 02 Dec 2010
Negligeable senescence happens when cells divide at a sufficiently rapid rate such that accumulation of "bad things/dammage" equilibrates with the speed of dillution of "bad things/dammage" by cell division
The central nervous system has mostly permanent neurons of high metabolic activity. I've heard that going from rat to man metabolic activity levels are similar*(this needs to be verified.). If that is so, something must've happened to allow for the 120+ year lifespan of at least some of such cells. We have to remember that the surrounding tissue is slowly failing around neurons.
Select quotes from a related article
I've heard that when taking the differences in activity with greater size into account, the overall rate of neuron metabolic activity is similar(from rat to man).Thus, the energy required per neuron to sustain the Na+/K+ pumps that restore ion gradients to generate electrical potentials is expected to increase in neurons with longer dendrites and axons.
...
Considering the relatively greater surface area of neuronal soma, dendrites, and axons that accompany brain enlargement, it has been estimated that each human neocortical neuron consumes 3.3 times more ATP to fire a single spike than in rats, and 2.6 times more energy to maintain resting potentials
...
link
Assuming the same holds for whales, similar metabolic rates and mostly permanent neurons, some of these are rumored to reach about 200 years(e.g. some are rumored to be candidates for negligible senescence.).
Either a.)they can export accumulating garbage somehow(This is what society does at a large scale, I don't see why it wouldn't work on a smaller scale.), b.) they generate exponentially less, c.) something else is going on.
whales have few cells? interesting
By ridiculous I meant ridiculously large numbers of cells.
Edited by Cameron, 02 December 2010 - 07:26 AM.
Cameron 24 Dec 2010
The prospect of removing cellular deposits of lipofuscin is of considerable interest because they may contribute to age related functional decline and disease. Here, we use a decapod crustacean model to circumvent a number of problems inherent in previous studies on lipofuscin loss. We employ (a) validated lipofuscin quantification methods, (b) an in vivo context, © essentially natural environmental conditions and (d) a situation without accelerated production of residual material or (e) application of pharmacological compounds. We use a novel CNS biopsy technique that produces both an anti-ageing effect and also permits longitudinal sampling of individuals, thus (f) avoiding conventional purely cross-sectional population data that may suffer from selective mortality biases. We quantitatively demonstrate that lipofuscin, accrued through normal ageing, can be lost from neural tissue. The mechanism of loss probably involves exocytosis and possibly blood transport. If non-disruptive ways to accelerate lipofuscin removal can be found, our results suggest that therapeutic reversal of this most universal manifestation of cellular ageing may be possible.-link