I'm not intellectually committed to some Programmed Theory of Aging so I have no need or interest in defending or explaining them. I'm a Longevity Science hobbyist, not a professional scientist. I'm mostly interested in aging theories insofar as they have implications for practice, witness my post of the factors associated with young and old blood plasma that Josh Mitteldorf posted about.
The studies discussing biological rejuvenation implicate Repair, the topic of this thread, and are interesting and have practical implications. It's important to realize that, even if Katcher's and Mitteldorf's Explanations of those Rejuvenation effects are BS, the effects actually took place, have been documented in studies, and need to be explained.
Katcher has, in fact, offered an explanation. I'd be thrilled to see a serious SENS based explanation of the Rejuvenation studies.
When can we expect it?
Edited by HighDesertWizard, 11 January 2015 - 06:51 PM.
I now believe that Healthful Rejuvenation options are possible for us today, even with our limited knowledge... I believe these options aren't so obvious because we don't actually believe they exist, and so we haven't pressed ourselves to creatively and rigorously engage with the scientific literature in search of them. My belief is founded on a couple personal experiences.
I once cured myself of Carpal Tunnel Syndrome by accident, by a means I now believe was Epigenetic. I posted about that experience here. The post following that one provides some evidence I believe makes an Epigenetic science Explanation as plausible as any other.
This thread about Repair Mechanism Rejuvenation would be more interesting if we were able, together, to brainstorm practicable and specific strategies for health disorder repair in ways comparable to what I've posted about previously. I believe the effort would be worthwhile.
Edited by HighDesertWizard, 11 January 2015 - 09:45 PM.
Josh Mitteldorf has usefully taken Katcher's paper further with discussion of what aged human blood has too much of or not enough of in How Young Blood Differs from Old...
Blood factors that we have too little of as we get older
melatonin, from pineal gland, controls daily cycle of sleep and waking
DHEA = dehydroepiandrosterone is a precursor of sex hormones and steroids
ubiquinone = CoQ10 is an anti-oxidant and electron transporter, used in mitochondria for energy production
thyroxine, produced in the thyroid, regulates many other hormones, stimulates activity
HSP70, heat shock protein, protects against muscle loss with age
NFk[/size]B, a cytokine which triggers inflammation
LH (luteinizing hormone) & FSH (follicle-stimulating hormone), associated with ovulation in women and sperm production in men. Increase late in life for both men and women.
CCL11 (a growth-inhibiting chemokine, see Villeda’s work above)
So... Too much NF-kB in the plasma as we get older, NF-Kb, an independent variable vis-a-vis aging in many other studies. No theory explanation here, just a couple other studies that are on topic in this thread, namely, the failure of the Adaptive Immunity repair mechanism. They also emphasize the importance of NF-kB expression to the aging process...
Between 2008 and 2010, Finnish scientists published several studies NF-kB and its critical importance for aging...
Innate and adaptive immunity are the major defence mechanisms of higher organisms against inherent and environmental threats. Innate immunity is present already in unicellular organisms but evolution has added novel adaptive immune mechanisms to the defence armament. Interestingly, during aging, adaptive immunity significantly declines, a phenomenon called immunosenescence, whereas innate immunity seems to be activated which induces a characteristic pro-inflammatory profile. This process is called inflamm-aging. The recognition and signaling mechanisms involved in innate immunity have been conserved during evolution. The master regulator of the innate immunity is the NF-kB system, an ancient signaling pathway found in both insects and vertebrates. The NF-kB system is in the nodal point linking together the pathogenic assault signals and cellular danger signals and then organizing the cellular resistance. Recent studies have revealed that SIRT1 (Sir2 homolog) and FoxO (DAF-16), the key regulators of aging in budding yeast and Caenorhabditis elegans models, regulate the efficiency of NF-kB signaling and the level of inflammatory responses. We will review the role of innate immunity signaling in the aging process and examine the function of NF-kB system in the organization of defence mechanisms and in addition, its interactions with the protein products of several gerontogenes. Our conclusion is that NF-kB signaling seems to be the culprit of inflamm-aging, since this signaling system integrates the intracellular regulation of immune responses in both aging and age-related diseases.
Molecular studies in model organisms have identified potent longevity genes which can delay the aging process and extend the lifespan. Longevity factors promote stress resistance and cellular survival. It seems that the aging process itself is not genetically programmed but a random process involving the loss of molecular fidelity and subsequent accumulation of waste products. This age-related increase in cellular entropy is compatible with the disposable soma theory of aging. A large array of host defence systems has been linked to the NF-κB system which is an ancient signaling pathway specialized to host defence, e.g. functioning in immune system. Emerging evidence demonstrates that the NF-κB system is activated during aging. Oxidative stress and DNA damage increase with aging and elicit a sustained activation of the NF-κB system which has negative consequences, e.g. chronic inflammatory response, increase in apoptotic resistance, decline in autophagic cleansing, and tissue atrophy, i.e. processes that enhance the aging process. We will discuss the role of NF-κB system in the pro-aging signaling and will emphasize that several longevity factors seem to be inhibitors of NF-κB signaling and in that way they can suppress the NF-κB-driven entropic host defence catastrophe.
Edited by HighDesertWizard, 15 January 2015 - 04:20 AM.
Another piece of a puzzle. Why would old cells switch to a less efficient, error-prone DNA repair? It would be interesting to know where this switch happens in relation to aging, is it up or downstream -? At this time in the game, as the accumulating damage theory contorts in its final throes, more and more data comes in in support of programmed aging. ..though this program could be something as simple as decline in the levels of 'youth factors' due to some specialized cells running out of telomeres.
why would evolution develop an aging program when most animals died, due to predation or infection, before they even had a chance to substantially age?
Group selection aside, aging is indispensable in human culture and science. Thank to it new generations don't have to always resort to violent, bloody revolutions in order to install changes that are long overdue. ..it's a sad fact that senior people are generally disinclined to change their opinion, especially when they have expressed it repeatedly in public, or, god forbid, wrote a book on the matter
Another piece of a puzzle. Why would old cells switch to a less efficient, error-prone DNA repair? It would be interesting to know where this switch happens in relation to aging, is it up or downstream -? At this time in the game, as the accumulating damage theory contorts in its final throes, more and more data comes in in support of programmed aging. ..though this program could be something as simple as decline in the levels of 'youth factors' due to some specialized cells running out of telomeres.
I suspect it's the latter, and don't think that damage is any less important than it ever was. In the above Mitteldorf blog post, Josh seems to be awed to discover the existence of DNA repair. I thought it was pretty cool too, um, thirty years ago when I was taking a graduate course devoted to it... Theory is a powerful thing in the hands of someone who really knows the details of the thing he's modelling. In the hands of a mathematician like Josh, it can be dangerous to attempt to apply it to biology. This switch from a better to a worse form of repair is interesting, but to snatch it as "support" for simulation results seems like a reach to me. The most likely explanation, as you suggest, is that the better version broke due to something changing. That change may well be communicated through a paracrine signal (youth factor), but until we understand the source of the change, there isn't much we can say about what theoretical model it supports or doesn't support.
why would evolution develop an aging program when most animals died, due to predation or infection, before they even had a chance to substantially age?
Group selection aside, aging is indispensable in human culture and science. Thank to it new generations don't have to always resort to violent, bloody revolutions in order to install changes that are long overdue. ..it's a sad fact that senior people are generally disinclined to change their opinion, especially when they have expressed it repeatedly in public, or, god forbid, wrote a book on the matter
I understand and agree with you about the importance of sweeping out the cobwebs, as it were, but aging initially evolved in an environment that was not particularly social. All social animals age, but so do non-social life forms. The fact that dictators die (along with saints, artists, and geniuses) is more of an artifact of everyone being tortured to death by their deteriorating organism than a cause of that tragedy. Thus I feel like my question still stands. I'd like to add another: Why do species (like mice) that experience high rates of predation have short lifespans, while species like naked mole rats (or humans, whales, clams, birds... ) that experience a low rate of predation have long lifespans? If there was a benefit in culling the ranks of a given species, shouldn't the aging rates be reversed? I think this is a big problem for the programmed aging hypothesis.
When I started this thread, the idea I wanted to advance, that seemed novel to me, was that we don't age, or, in SENS terminology, don't accumulate damage while we're young, because of the efficient repair mechanisms. Unexpectedly, this thread spilled into critique of SENS. Though I did not plan it this way, now that I have been told that I don't understand a thing, naturally I can't leave this latest presentation by de Grey without a comment.
As usual, throughout the talk de Grey does not mention existing repair mechanisms, as if this is something irrelevant. Here is his central tenet again:
"Metabolism -- in other words, the entire network of processes that keep us alive from one day to the next -- causes damage to the body throughout life, even starting before we're born, and that damage is harmless for a long time, but then in late life the damage translates in various pathologies of the old age." "..... geriatrics is never going to work, because the damage that causes all these pathologies is continuing to accumulate at the absolutely inevitable consequence of being alive .."
Comment#1: Damage does indeed occur all the time, but it is not harmless. Damage is rendered harmless because it is efficiently repaired, though after 25-35 (yes, there is a wide variation in this) the efficiency of these repairs begins to diminish.
At around 12:45 - 13:30 de Grey speaks of CR as means to slow down metabolism "in the manner that slows down the accumulation of damage". Comment#2: the life extension that is achieved as a result of CR is NOT due to slower metabolism or slower accumulation of damage. It is entirely due to urpegulation of the repair mechanisms. This is an important distinction.
At around 17:35 he offers:
"rather than slow down the creation of damage, ...we propose to go and periodically repair the damage itself. ...And of course this is what we already do with inanimate objects -- going back to my point that human body is merely a machine."
At 34:38 he starts talking about amyloidoses, the #1 killer of supercentenarians. He says, the aim is to "neutralize the material." "We want to be selective for the type of protein that aggregates into this amiloid form." Comment#3: the anti-aging community is still largely unaware about antimicrobial peptides and various amyloids they form as part of the innate immune response (in short, these peptides congregate into the 'nets' that literally trap the pathogens). It is the fact that the body sustains the most damage as a side effect of its own immune responses. This damage is repaired after the infection is cleared, though of course this does not happen with persisting infections. So, amyloidoses could be the consequence of subclinical chronic infections; and the dangers of "neutralizing" an immune response without addressing its target pathogen was already discussed in the other thread.
Finally, at 36:46 a questioner points out that inanimate objects don't have the ability to self-repair. He says, "We can repair DNA, proteins, etc, such that inanimate objects cannot." To this de Grey replies:
"Yes, the body creates itself from a single cell all the way up to an adult, and that's a remarkable phenomenon, but that's a phenomenon that is completely separate from accumulation of damage, which also happens starting from a single cell even before we are born, but which happens as a non-programmed side effect of what the body is programmed to do.."
Comment#4 above is not quite true. Protein damage is inseparable from metabolism. However, protein repairs is also an integral part of metabolism. Without both life simply cannot go on.
Around 39:55 regarding the difference between the living and inanimate objects, de Grey says:
"With regard to the other thing you mentioned, that we have this inbuilt self-repair, yes, that's a very big difference, but that's the difference that makes my point stronger, because it means that we have less to do to augment the existing program repair that we already have."
Yeah, here I also thought, at last! Alas, de Grey did not mean augment as in upregulate. He meant it as in addition to: "..the repair is the same, but we have to do less of it, because so much of it is happening without our efforts."
That's all de Grey has to say about our fabulous repair mechanisms. But what if it turns out that aging is not due to damage that starts accumulating in utero but, as latest evidence suggests, cells behave as either young or old according to some signals in their environment? If so, then whatever SENS-inspired repair therapies will manage to accomplish will not last, just like the results don't last after a fast. After a fast it's very hard to maintain that newly found balance. It seems just a bit of wrong food or, a wrong quantity of it, can cause one to slip into the old, familiar groove, following which much of what was gained is lost. I guess this is similar to putting newly repaired cells into an old environment, which causes them to promptly revert back to senescent phenotype. If indeed aging turns out to be due to declining levels of some 'youth factors', then niner's objections to fasting as something "not very encouraging" 'cause it "only works in the young" could be equally applied to SENS.
Repair mechanisms exist in our bodies - every body seem to agree with this,
The repair mechanisms fail progressively - also seem every body agrees.
But one thing still is an issue, that no one so far pointed out - not all kinds of damage can be repaired. For example, not all tissues and not all cells can regenerate. There are cells, in our bodies, which if get killed, are lost forever. If you wound your hand, it will heal, yes, but there will be a scar, not an epithelium tissue. If you loose a gloerul it is lost forever. The most important cells in all of the organs virtually do not regenerate their number.
Repair mechanisms exist in our bodies - every body seem to agree with this,
The repair mechanisms fail progressively - also seem every body agrees.
But one thing still is an issue, that no one so far pointed out - not all kinds of damage can be repaired. For example, not all tissues and not all cells can regenerate. There are cells, in our bodies, which if get killed, are lost forever. If you wound your hand, it will heal, yes, but there will be a scar, not an epithelium tissue. If you loose a gloerul it is lost forever. The most important cells in all of the organs virtually do not regenerate their number.
The loss of regeneration capacity of tissues and organs is closely related to stem cell depletion.
This process already takes place in the very young, when multipotent progenitor cells are switched off by the developement program.
Is stem cell depletion in the adult body an "unintended" accident or a continuation of this "switch-off" phenomenon?
The loss of regeneration capacity of tissues and organs is closely related to stem cell depletion.
This process already takes place in the very young, when multipotent progenitor cells are switched off by the developement program.
Is stem cell depletion in the adult body an "unintended" accident or a continuation of this "switch-off" phenomenon?
Adult stem cells exist in most mammalian organs and tissues and are indispensable for normal tissue homeostasis and repair.In most tissues, there is an age-related decline in stem cell functionality but not a depletion of stem cells. Such functional changes reflect deleterious effects of age on the genome, epigenome, and proteome, some of which arise cell autonomously and others of which are imposed by an age-related change in the local milieu or systemic environment. Notably, some of the changes, particularly epigenomic and proteomic, are potentially reversible, and both environmental and genetic interventions can result in the rejuvenation of aged stem cells. Such findings have profound implications for the stem cell–based therapy of age-related diseases.
Human adipose tissue is an ideal autologous source of mesenchymal stem cells (MSCs) for various regenerative medicine and tissue engineering strategies. Aged patients are one of the primary target populations for many promising applications. It has long been known that advanced age is negatively correlated with an organism’s reparative and regenerative potential, but little and conflicting information is available about the effects of age on the quality of human adipose tissue derived MSCs (hAT-MSCs).
Methods
To study the influence of age, the expansion and in vitro differentiation potential of hAT-MSCs from young (<30 years), adult (35-50 years) and aged (>60 years) individuals were investigated. MSCs were characterized for expression of the genes p16INK4a and p21 along with measurements of population doublings (PD), superoxide dismutase (SOD) activity, cellular senescence and differentiation potential.
Results
Aged MSCs displayed senescent features when compared with cells isolated from young donors, concomitant with reduced viability and proliferation. These features were also associated with significantly reduced differentiation potential in aged MSCs compared to young MSCs.
Conclusions
In conclusion, advancing age negatively impacts stem cell function and such age related alterations may be detrimental for successful stem cell therapies.
if the loss of tissue regeneration capacity is due to damage accumulation in the stem cell pool, xEva could hit the mark.
The term "nonfunctional stem cells" is an oxymoron. If a stem cell is converted into a senescent cell, then the cell is lost for tissue regeneration, right?
Besides, I doubt that the stem cell number remains constant over a lifetime:
Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis
The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages.
if the loss of tissue regeneration capacity is due to damage accumulation in the stem cell pool, xEva could hit the mark.
The term "nonfunctional stem cells" is an oxymoron. If a stem cell is converted into a senescent cell, then the cell is lost for tissue regeneration, right?
Besides, I doubt that the stem cell number remains constant over a lifetime:
Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis
The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages.
I don't think you read what I posted. So I'll copy it again and maybe this time you will.
Aged MSCs displayed senescent features when compared with cells isolated from young donors, concomitant with reduced viability and proliferation.
Oh and another thing, there's nothing wrong with xEva's idea if you consider it as part of the picture. It doesn't really go against wear and tear as much as she thinks. In fact it doesn't go against it at all, I've already spoken to her about it in another thread.
And if xEva is correct, then we may be able to take out a stem cell, fix it, implant it back, and rejuvenate the tissue, right? This can be the life saving strategy !!!!
And if xEva is correct, then we may be able to take out a stem cell, fix it, implant it back, and rejuvenate the tissue, right? This can be the life saving strategy !!!!
The loss of regeneration capacity of tissues and organs is closely related to stem cell depletion. This process already takes place in the very young, when multipotent progenitor cells are switched off by the developement program.
Is stem cell depletion in the adult body an "unintended" accident or a continuation of this "switch-off" phenomenon?
...
Stem cells don't get depleted. They get irreversibly damaged and ultimately nonfunctional.
The current study shows that telomere dysfunction induces alterations in the stem cell environment that lead to HSC intrinsic deficiencies that ... can be induced by environmental alterations. ... These findings could have implication for therapeutic approaches aiming to improve the function of aged stem cells to improve organ maintenance. The systemic factors that impair HSC function in response to telomere dysfunction induced changes in the environment remain yet to be defined. It has been shown that telomere dysfunction in telomerase knockout mice induces the expression of marker proteins of DNA damage in blood serum . ...A systemic analysis of these regulatory networks could help to identify novel targets for therapies aiming to improve stem cell function during aging.
From the abstract: There is growing evidence that telomere dysfunction can contribute to human aging. Telomere dysfunction limits lymphopoiesis in aging telomerase knockout (mTerc−/−) mice primarily by the induction of stem cell–extrinsic alterations. ... The impairment in B and T lymphopoiesis in aging telomere-dysfunctional mice was mainly due to alterations of the systemic environment. Telomere dysfunction had no significant cell-autonomous effects impairing the function of thymic or bone marrow niches in supporting B and T lymphopoiesis. Moreover, age-related alterations in the cellular composition of the thymic epithelium in telomere-dysfunctional mice were rescued by transplantation of the thymus into a wild-type environment; these rejuvenated thymi supported normal T lymphopoiesis in recipient mice. Together, these data place alterations in the systemic environment on top of the hierarchy of events limiting lymphopoiesis in response to telomere dysfunction.
In other words, it looks like there are systemic factors that determine whether stem cells behave as young or old. One of these factors has been tentatively identified GDF11 (discused here http://www.longecity...myo-oa-trial/).If this pans out, that would be very good news, 'cause it's relatively straightforward to deliver necessary peptides into the circulation (via an IV perhaps).
And if xEva is correct, then we may be able to take out a stem cell, fix it, implant it back, and rejuvenate the tissue, right? This can be the life saving strategy !!!!
The simplest way to test xEvas hypothesis is still to produce repair therapies.
I don't see how an experiment may prove or disprove my observation of a simple, plainly seen fact that we don't age --i.e. don't accumulate damage-- while we're young. This is so obvious that it even sounds like an oxymoron.
And I am still to see a study that shows "damage accumulation" (beyond passing side-effects of an illness) in a young cohort. Not to go too far, the study linked by corb just above compares people under 30 with those over 60 and confirms that regenerative capacity is impaired in old age (>60). But where is the study that shows that a similar decline takes place in young groups, say, 20-25 compared to 25-30? This is what's claimed by the accumulating damage theory. Based on what?
EDIT: @LeeYa, seivtcho. Sorry guys I did not see your posts till now. Yes, it's starting to look like all that maybe needed to switch on the endogenous repair mechanisms is to introduce into the circulation some 'youth factors' like GDF11 ..I know, sounds too good to be true, but.. whataheck
While there is a lot of trueth in your theory, don't underestimate the other theories. They are correct too. For example the wear ant tear theory: your teeth are being weared off each time you eat. The teeth of the very old people (in the cases when they have teeth) are weared off. My grand mother has two metal crowns, placed more than 30 years ago, and the metal is weared off (filed away) to such an extend, that the metal teeth has lost their form, and look like a flat surface,
In other words, it looks like there are systemic factors that determine whether stem cells behave as young or old. One of these factors has been tentatively identified GDF11 (discused here http://www.longecity...myo-oa-trial/).If this pans out, that would be very good news, 'cause it's relatively straightforward to deliver necessary peptides into the circulation (via an IV perhaps).
Unfortunately, GDF 11 and other circulating factors seem to me a little bit overhyped.
Based on this hypothesis of systemic rejuvenation from young plasma, what would you expect from injecting plasma from young mice to old mice?
Aged Mice Repeatedly Injected with Plasma from Young Mice: A Survival Study
While there is a lot of trueth in your theory, don't underestimate the other theories. They are correct too. For example the wear ant tear theory: your teeth are being weared off each time you eat. The teeth of the very old people (in the cases when they have teeth) are weared off. My grand mother has two metal crowns, placed more than 30 years ago, and the metal is weared off (filed away) to such an extend, that the metal teeth has lost their form, and look like a flat surface,
well, dental germ implantation every 30 years should solve this particular issue
lol you can have the germ implant even longer. As long as you have a dental root and enough bone, it will be able your dentist to make you a crown, and you will have a tooth in your mouth.
For a long time I believe, that the stem cells are the answer for how we can live forever.
Lol. Not exactly. Induced pluripotent cells are usual cells (somatic cells, non stem cells), that are turned into stem cells.
What I ment is to take an old an inactive stem cell, recover it, and implant it back.
Fibroblasts typically, not just any random cells - and fibroblasts are not that remote from stem cells.
And yes senescent fibroblasts as well.
But I feel like what you're asking is whether someone can do it in vivo to your existing stem cell populations.
Well seeing how they're tumorigenic in culture... you see how things would go, I believe.
There were experiments with mice, back when telomerase was the hype. They made mutant mice that were producing telomerase and basically had stem cells that would never become senescent. They all died from cancer.
Ah which reminds me, all the mice in the GDF11 experiments died as well. In a timely manner, no life extension was recorded.
There were experiments with mice, back when telomerase was the hype. They made mutant mice that were producing telomerase and basically had stem cells that would never become senescent. They all died from cancer.
Ah which reminds me, all the mice in the GDF11 experiments died as well. In a timely manner, no life extension was recorded.
That's a good point. No life extension was recorded, but what about the damage, i.e. did it stop accumulating or at least slowed down? IOW, did the animals exhibit 'youthful phenotype' or continued to age as usual? What did they die of, mostly?
Re GDF11 beying overhyped, surely, GDF11 itself may turn out downstream from some 'real', thus far unidentified factor or factors. ..though I find the whole idea that a 'right environment' can profoundly affect how cells behave very encouraging. ..especially since it seems to correlate with my own studies of fasting.
That's all de Grey has to say about our fabulous repair mechanisms. But what if it turns out that aging is not due to damage that starts accumulating in utero but, as latest evidence suggests, cells behave as either young or old according to some signals in their environment? If so, then whatever SENS-inspired repair therapies will manage to accomplish will not last, just like the results don't last after a fast. After a fast it's very hard to maintain that newly found balance. It seems just a bit of wrong food or, a wrong quantity of it, can cause one to slip into the old, familiar groove, following which much of what was gained is lost. I guess this is similar to putting newly repaired cells into an old environment, which causes them to promptly revert back to senescent phenotype. If indeed aging turns out to be due to declining levels of some 'youth factors', then niner's objections to fasting as something "not very encouraging" 'cause it "only works in the young" could be equally applied to SENS.
If our repair mechanisms were really that fabulous, we wouldn't need SENS. But they aren't that fabulous. Aubrey doesn't say much about them because they ultimately fail, and he wants to improve on that state of affairs. If SENS ends up working spectacularly, you might need an infusion every ten years or so. Even if you needed treatment on a yearly basis, so what? It's not like you're going to fall apart a few minutes after you leave the treatment center. If youth factors are involved in aging decline, then we will either replace them or we will figure out how to upregulate them. However, there is zero evidence that aging factors alone can fix glycation damage, or eliminate senescent zombie cells, or unclog lysosomes that are full of indigestible junk. That is the kind of thing that SENS is trying to fix.
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