Posted 16 March 2015 - 10:55 PM
Am I right in thinking that there are no deaths from dementia in Monaco. Do they know something the rest of us don't? I wouldn't be surprised if I am wrong though but if not...
If the statistic is based on a single year it's not impossible for a country of 30000 to have 0 dementia related deaths.
Posted 16 March 2015 - 11:03 PM
Am I right in thinking that there are no deaths from dementia in Monaco. Do they know something the rest of us don't? I wouldn't be surprised if I am wrong though but if not...
Did you mean Morocco? Monaco is the place where people with $100M bank accounts land their private jets to enjoy a weekend of high stakes gambling. 
It's simple genetics. Most of sub-saharan Africa has low percentage of the APOE-4 gene that puts you at risk for Alzheimers. To contrast, Scandinavia has one of the highest concentrations of APOE-4:
http://onlinelibrary...9.6340301.x/pdf
And here is the distribution of Alzheimer's by country:
http://www.worldlife...tia/by-country/
I have a very plausible theory that connects dietary practice to genetics that explains most of that variation by country, but this is supposed to be a senolytics thread.
Posted 16 March 2015 - 11:50 PM
... if someone wants to try a DQ cocktail they better have a plan to show the results, in at the very least, semi scientific manner. It's the least they can do for the incredible pleasure of puking their guts after that nice dose of D at least.
Dasatinib is not a "puke your guts out" kind of chemotherapy. It's a targeted drug that inhibits a particular kinase. That doesn't mean it's free of side effects, but a single dose probably wouldn't be the end of the world. Side effects are more common in sicker patients who have failed on other regimens. Healthy people would probably weather it pretty well. I think I'd be more worried about barfing from a quercetin megadose...
Posted 17 March 2015 - 03:33 PM
Quercetin and dasatinib acted on totally different tissues. Quercetin worked on endothelial lining and dasatinib on fat cells. So why would you need to take both?...
I wonder if the effects were separate or if there is some synergism?
From Examine.com:
Resveratrol's effects on fat metabolism (inhibiting adipogenesis) are synergistic with the phytonutrient Genistein, of which the effects of synergism were roughly double the sum of the parts.[246] At 50umol/L, Genistein increased apoptosis of preadipocytes and mature adipocytes by 46±9.2% and Resveratrol at 100umol/L by 46±7.9%, whereas the combination was measured at 242 ± 8.7%. Similar synergism was seen in decreasing lipid accumulation, and the decreases in adipogenesis may have been through downregulation of PPARy.
The combination is also able to increase Jun-N-terminal phosporylation when no compound in isolation was able to, and increased fat lipolysis by 25.5±4.6% when no compound in isolation did.
14.2. Quercetin
Quercetin was also synergistic with Resveratrol in protection of blood vessels[247] and inhibition of adipogenesis and slightly more potent than Genistein in the overall percent synergism.[248]
Combining all three bioflavonoids showed further synergism and low-dosing the three can provide cumulatively similar benefits at cheaper costs.
http://examine.com/s...nts/Resveratrol
So it would seem that the above is a roundabout way of saying that Quercetin synergises with Resveratrol to cause apoptosis of preadipocytes and mature adipocytes.
Which means that by itself it has these effects to a lesser degree than with resveratrol.
This means that it might have a synergistic effect with Dasatinib..?
_____________________________________________________________________________
Examin.com's page on Quercetin is also well worth reading.
Of note:
An increase in the amount of intestinal permeability induced by training in the heat has been noted with quercetin supplementation, which is an adverse event; the influence
of quercetin at rest is uncertain.
So... hitting the gym after your Q+D dose to improve their distribution throughout the body may not be a great idea?
3. Pharmacology
After oral ingestion of quercetin, it is taken up from the gut into the liver. The conjugate of quercetin influences its absorption rates. At least intestinally, quercetin glycosides (food source) were found to have a 52+/-15% uptake, quercetin rutinoside (tea) has a 17+/-15% uptake, and supplemental quercetin aglycone had a 24+/-9% uptake.
One pharmacokinetic study in humans following consumption of 500mg Quercetin (as aglycone) noted that the delivery of Quercetin chews had a Cmax of 1051.9+/-393.1ug/mL at Tmax of 3.66 hours, with the Cmax and Tmax of Food bar format and juice suspension reaching 698.1+/-189.5μg/L (in 2.3h) and 354.4+/-87.6μg/L (4.7h), respectively.[16] This study had all forms using QU995, and was unable to conclude any significant differences between groups due to higher variability (just different average).
Appears to per se have a moderate to low bioavailability, depending on the source
Due to enhanced lymphatic release of Quercetin following administration of Long-Chain Fatty acids (LCFAs), it is thought that the formation of micelles from LCFAs can enhance the apparent bioavailability of Quercetin.
Quercetin is a potent inhibitor of intestinal sulfurotransferases, and has some activity on hepatic sulfurotransferases as well.[18] This mechanism may increase bioavailability of compounds that undergo extensive intestinal metabolism via this method, like Resveratrol.[19]
Interacts with intestinal conjugation enzymes, which may predispose Quercetin to nutrient-nutrient interactions
3.2. Circulating Quercetin
Acute administration of 2,000mg quercetin aglycone (in a food matrix) increases circulating quercetin aglycone to a concentration of 4.76+/-2.56μM at one hour.
250-500mg of the aglycone has been detected in the blood within 15-30m and peaks in the 120-180m range, reaching baseline concentrations within 24 hours.[21] 730mg of the aglycone has been noted to increase plasma concentrations from 695+/-103nM to 1419+/-189nM.
Supplementation of 50, 100, and 150mg quercetin (as dihydrate) can increase blood concentrations of quercetin to 92.2nM, 171.8nM, and 316.2nM respectively; the largest dose was also associated with a large range of serum concentrations, from 240–1292nM[23]
Basal concentrations of quercetin in the blood (from food intake) average 53.6nM, with a large range of 30–163nM.
3.3. Metabolism
After the liver, quercetin exists in the blood solely as quercetin glucuronides.[24] Regardless of initial source, all forms of quercetin undergo hydrolysis and get glucuronidated in the liver before being released into systemic circulation.
3.4. Neural Pharmacology
In pigs, feeding of quercetin aglycone at 50mg/kg BW increased neurological concentrations to 0.02uM,[25] while another study noted levels of 0.22uM with a dosage of 500mg/kg BW.[26]
Quercetin is a highly polar (water-soluble) compound, but seems to be able to cross models of the blood brain barrier.[27][28] Mixed onion flavanoids (of which Quercetin comprises a large amount) appear to have around a 60% efficacy in crossing the BBB.
5. Cardiovascular Health
In persons with stage I hypertension given 730mg quercetin (aglycone in two divided doses) over a month, supplementation was associated with reductions in both systolic (−7+/-2mmHg) and diastolic (-5+/-2mmHg) independent of improvements in oxidative status; this benefit was not seen in nonhypertensive persons. The changes in blood pressure did not persist following supplement cessation.
http://examine.com/s...etin#summary3-0
Edited by Logic, 17 March 2015 - 03:36 PM.
Posted 18 March 2015 - 12:46 AM
@ niner: I admire your enthusiasm for this drug combination, inasmuch as I personally prefer everolimus. If someone wants to step up to the plate and start a reporting thread, I'm all for it. There are plenty of experts here who can recommend tests for you to do, before and after. If this works in seniors, it should produce some obvious effects; if not, then frankly it doesn't rejuvenate in any socially relevant manner. I do agree that the effects might be subclinical in healthy young people, however. Any takers? (BTW quercetin doesn't bother me at all, probably because it's so very unbioavailable; I doubt that I'm unique in this regard.)
@ corb: The long lifespan in Bulgaria is perhaps due to your yoghurt intake; they don't call it L. bulgaricus for nothing. Moreover it provides the heart with its preferred lactic acid fuel, and probably provides a source of ameal peptide for blood pressure. Not that living in the countryside and climbing hills all day is unrelated to the risk reduction.
SCNT or IPSC are ways of making unlimited stem cell volumes from individual cells, no matter how old they are. But the downside is that, until we have the means to artificially correct genetic errors with statistical analysis and zinc finger nucleases, the resulting cultured cells are going to behave like "old" cells. That's why I advocate freezing: worst case, if we freeze the wrong cell type, we can thaw them out and hack them using SCNT or IPSC into a comparatively younger cell culture, depending on the freezing age.
Posted 18 March 2015 - 06:48 AM
Is anyone interested in doing a group buy? Maybe people could post here if they are interested.
I would be interested.
I think we might only need a single treatment. I would want about 5-10 Dasatinib pills and that's about as much as I could afford too.
We would need some quality assurance though so we don't get scammed.
Posted 18 March 2015 - 09:37 PM
On the basis of this article, The Achilles’ Heel of Senescent Cells: From Transcriptome to Senolytic Drugs, I took 3200 mg of quercetin twice per day for three days last weekend. Now, three days later, my skin is clearer. Pigmented areas on my arms that I closely watch have noticeably faded. There were no side effects. I am 59 years old.
Posted 18 March 2015 - 10:48 PM
On the basis of this article, The Achilles’ Heel of Senescent Cells: From Transcriptome to Senolytic Drugs, I took 3200 mg of quercetin twice per day for three days last weekend. Now, three days later, my skin is clearer. Pigmented areas on my arms that I closely watch have noticeably faded. There were no side effects. I am 59 years old.
What form of quercetin? Theoretically, the human one-time dose based on mice dose would be 3500 mg or less, but a single day not three days. The problem is bioavailability is poor, so you might be getting effectively nothing or a very small dose.
Posted 18 March 2015 - 10:49 PM
On the basis of this article, The Achilles’ Heel of Senescent Cells: From Transcriptome to Senolytic Drugs, I took 3200 mg of quercetin twice per day for three days last weekend. Now, three days later, my skin is clearer. Pigmented areas on my arms that I closely watch have noticeably faded. There were no side effects. I am 59 years old.
Really!?
I was just thinking out loud when I said one may see the difference in ones skin from Q+D.
Strangely I took VRP's Extension Resveratrol and my only small pigmented area on my chin started itching and flaking.
I scratched it and its flaked of and is gone.
VRP's Extension Resveratrol contains:
Trans-Resveratrol 300 mg
Quercetin 50 mg
Red Wine Polyphenols 10 mg
i took 1 tablet, 2x per day for about 3 weeks.
I cant believe that so little Quercetin was what did the trick..?
Unless... Resveratrol improves the bioavailability of Q and visa-versa???
Edited by Logic, 18 March 2015 - 10:50 PM.
Posted 18 March 2015 - 11:04 PM
I weigh about 70 kg, so by simple math the 50 mg/kg dose given to the mice comes to 3500 mg for me. I couldn't be sure of the bioavailability or other factors, and my experience with lower doses quercetin didn't show any side effects, so I just went ahead and took the heavy dose I described using NOW brand quercetin dihydrate (800 mg) + bromelain (165 mg), 4 capsules twice per day.
Posted 19 March 2015 - 12:54 AM
For completeness, while mega-dosing quercetin I took my normal doses of the following daily supplements: pterostilbene (100 mg) , icariin (100 mg), resveratrol (1000 mg) and nicotinamide riboside (1000 mg).
Edited by Fafner55, 19 March 2015 - 12:57 AM.
Posted 19 March 2015 - 09:47 AM
I have been in contact with Nyles. If you are interested in getting some Dasatinib then please either post here or contact me with pm. Better to get in quick because I don't want this to drag out. This is supposed to be 99% pure. Once I have a few more interested, I will pass the info to Nyles. Please don't contact Nyles directly just yet, I would like to keep this orderly for him. You will ultimately be dealing with Nyles directly, not me, I'm just trying to co-ordinate it.
PLEASE NOTE: This is for testing on your rat only!! All communication with Nyles should only indicate unambiguously that this is for your pet rat.
Posted 20 March 2015 - 05:52 AM
On the basis of this article, The Achilles’ Heel of Senescent Cells: From Transcriptome to Senolytic Drugs, I took 3200 mg of quercetin twice per day for three days last weekend. Now, three days later, my skin is clearer. Pigmented areas on my arms that I closely watch have noticeably faded. There were no side effects. I am 59 years old.
In this post:
http://www.longecity...ndpost&p=719547
You attribute the fading age spots to high dose C60oo...??
I also started taking high dose C60oo at the same time as the RSV and Q mix, so the age spot reversal claim/s are ... murky at best.
Posted 20 March 2015 - 12:10 PM
On the basis of this article, The Achilles’ Heel of Senescent Cells: From Transcriptome to Senolytic Drugs, I took 3200 mg of quercetin twice per day for three days last weekend. Now, three days later, my skin is clearer. Pigmented areas on my arms that I closely watch have noticeably faded. There were no side effects. I am 59 years old.
In this post:
http://www.longecity...ndpost&p=719547
You attribute the fading age spots to high dose C60oo...??
I also started taking high dose C60oo at the same time as the RSV and Q mix, so the age spot reversal claim/s are ... murky at best.
Logic, you make a good point. I had stopped taking C60-OO and my age spots had returned within a few weeks. Brown also returned to my eyes. Then began taking 22 mg C60-00 on 2015-03-07 and again on 2015-03-15, coincident with Q+R on March 13-15. These treatments overlapped. I can add that my age spots have continued to fade since 3-15 without taking either C60-OO or Q+R.
I will stop taking C60-OO for the next month to see if my age spots return as before and will report back.
Posted 20 March 2015 - 03:27 PM
Because I had access to 100mg (and only 100mg) I took 25mg of Dasatinib last night with 800mg of Quercetin to see how I'd react to it. I had weird dreams and woke for an hour in the middle of the night. This morning I feel heavy but not awful. I plan on taking 75mg with a yet unknown amount of Quercetin in 2 hours.
The literature says can be taken on an empty or full stomach, I'm going with full.
Posted 20 March 2015 - 04:06 PM
Because I had access to 100mg (and only 100mg) I took 25mg of Dasatinib last night with 800mg of Quercetin to see how I'd react to it. I had weird dreams and woke for an hour in the middle of the night. This morning I feel heavy but not awful. I plan on taking 75mg with a yet unknown amount of Quercetin in 2 hours.
The literature says can be taken on an empty or full stomach, I'm going with full.
That's brave. Please keep us posted on this. I'm guessing you got it via some kind of one-chance opportunity?
Posted 21 March 2015 - 09:56 AM
I weigh about 70 kg, so by simple math the 50 mg/kg dose given to the mice comes to 3500 mg for me. I couldn't be sure of the bioavailability or other factors, and my experience with lower doses quercetin didn't show any side effects, so I just went ahead and took the heavy dose I described using NOW brand quercetin dihydrate (800 mg) + bromelain (165 mg), 4 capsules twice per day.
I was just wondering if the BSA (Body Surface Area) which is a way to translate dosage from animal to humans can be applied here for Quercetin. Using the conversion for mice given HERE, your 50 mg/kg dose for 70 kg would be much lower, i.e. 3500 mg x 3/37 = 284 mg I think. But there is the problem of pharmacokinetics of absorption though. Can someone enlight this point?
Posted 21 March 2015 - 11:13 AM
Here is full text to the study in question:
http://onlinelibrary.../acel.12344/pdf
@Greenpower, this study looks at lifespan and healthspan. They recorded increase in healthspan and no decrease in lifespan. So how can you possibly hypothesize shortened telomeres from that experimental outcome? Shortened telomeres should decrease lifespan, and you would think that it would also decrease healthspan by rapidly increasing disease incidence in the last 10% of life. None of that happened here?
And if shortening of telomeres does not affect lifespan or healthspan, then what would that say about our understanding of the importance of telomere shortening in aging?
I think you have not called out the really amazing part of this study. They got six months of benefit from this therapy by taking the drug ONCE!!! In other words, they induce senescent cell death very rapidly using these drugs, then the organism is allowed to regain its internal environment without interference from drugs. That's an extremely attractive tactic since it avoids long-term side effects from continuous use of the drugs that the study may not have seen.
It looks like the drugs had an effect of lowering proliferating (healthy) cells as well senescent cells. But the remaining tissues have a higher percentage of healthy cells, so presumably once the organism fully recovers from the treatment that is the reason they see better health.
Can someone guide us what is the human-equivalent dose of Quercetin corresponding to 10 uM in a mouse? Does Quercetin survive digestion if you take it in pill form? It looks like the mice were dosed orally about 50 mg/kg of Quercetin.
The other drug they studied is a chemotherapy drug. That would be a bit crazy to self-administer, even if you could obtain it.
The whole discussion online about telomerase-activating and telomerase-inhibiting substances is just confused. There is a big difference between saying a substance activates or inhibits telomerase in vitro, and actually measuring longer or shorter telomeres after therapy in vivo. Reading many of the studies, you get the distinct impression that the actual biology is way more complex than our understanding of it. You can read 10 studies on Resveratrol and Quercetin and end up not having a clue about what the actual end result will be on telomeres in vivo.
I point out a risk, which I could argue is not exactly the same as making a hypothesis. I will confess I haven't read all of the paper, but did some quick searching for key concepts which I expected to find.
As the authors write: Effects of senolytic drugs on healthspan remain to be tested in chronologically aged mice, as do effects on lifespan.The mice used in the test also model human XFE progeria, have
features resembling accelerated aging with a lifespan of 6 months (Dolleet al. 2011) and spontaneously develop progressive age-related chronic degenerative diseases (Gregg et al. 2011).
I think this is great news for persons suffering from Progeria. There may be a new method of treatment in the pipeline which might have a tremendous impact on quality of life and burden of age-related chronic diseases.
However, translated to human terms, not many people with Progeria seem to live above the age of thirteen. I don't see any references in the paper to whether the mice actually lived longer than mice which model human XFE progeria usually do. I wouldn't be surprised if these mice did get a moderate life extension effect by removing old no-longer working cells and replacing them with newly replicated working cells. Please consider that these mice were after all suffering from a disease of accelerated aging where the organs in a very short time would be full of old non-working cells. I do however not expect mice without a disease of acceleratred aging to extend their life spans in the same degree.
As for an hypothesis. Let's for the arguments sake assume that most cells can only divide about 50 times before their telomeres get so short they are no longer able to replicate. If you kill of all senescent cells as well as the "soon-to-be senescent but working quite well at the moment" cells, the remaining cells are likely to start replicate faster, taking the recently died off cells places. The first times you kill off these older cells you are likely to get organs and a body which work better because all the old cells have been eliminated. However, for each time you repeat the process, the remaining cells will get shorter telomeres and will themselves get closer to the point where they will no longer be able to work or replicate. My hypothesis is that if you repeat this process too many times, your cells will age rapidly to the point where most of the cells will go into apoptosis, making the organs they are part of to fail. You should be able to test this hypothesis by repeatedly administrating the drugs on people which are not suffering from accelerated aging. I expect the results to be people with greater average health span but with shorter average life span.
This method of attacking the problem of aging reminds me of one described in the Hugo Award Novella Fountain of Age. It describes a method of rejuvenation which upon administration turns the subject back to being young again, giving them an additional almost perfect health span of twenty years. The unfortunate side effect of this administration is that they will also have an expected remaining life span of the same twenty years. Many people in the novella did however prefer to end their life with a period of 20 years being young again and with perfect health, rather than living on for perphaps another 40 years as old and with a failing body.
Edited by GreenPower, 21 March 2015 - 11:16 AM.
Posted 21 March 2015 - 01:05 PM
As for an hypothesis. Let's for the arguments sake assume that most cells can only divide about 50 times before their telomeres get so short they are no longer able to replicate. If you kill of all senescent cells as well as the "soon-to-be senescent but working quite well at the moment" cells, the remaining cells are likely to start replicate faster, taking the recently died off cells places. The first times you kill off these older cells you are likely to get organs and a body which work better because all the old cells have been eliminated. However, for each time you repeat the process, the remaining cells will get shorter telomeres and will themselves get closer to the point where they will no longer be able to work or replicate. My hypothesis is that if you repeat this process too many times, your cells will age rapidly to the point where most of the cells will go into apoptosis, making the organs they are part of to fail. You should be able to test this hypothesis by repeatedly administrating the drugs on people which are not suffering from accelerated aging. I expect the results to be people with greater average health span but with shorter average life span.
It's not that simple.
Some stem cells can keep their telomere length completely flatlined throughout your life, if we use telomeres as a measure of aging, your muscles never truly age. Their stem cells are just as capable of replacing muscle in your 80s as they are in your 20s - of course disregarding the fact that they can't because it's their environment that has changed. No correlation has been found between satellite cell viability, quantity and age related muscle wasting - and believe me (or check pubmed 
), people have tried to find it for at least three decades.
Senescent cells can force other cells into senescence long before they've reached their Hayflick limit. In a way by simply being in a tissue the senescent cells already do what you fear removing them will accomplish. And much faster.
Mathematically the first organ capable of reaching the Hayflick limit in your body is the thymus. At age 125. No one has reached even close to that age so we can't know if it's a real possibility for all cells of an organ to go into senescence. And even if it happens, well, there's always transplantation.
Most people die from pathologies caused by chronic inflammation and impaired cellular turnover, so removing senescent cells gives the people who were going to die in their 60s and 70s from a CVD or cancer a bit of extra time - or maybe a lot of extra time, we'll see.
It's very straightforward, I'd even say it's in line with the mainstream medical thinking - which is good, it will be incorporated into medicine faster than most other proposed anti aging therapies.
Posted 21 March 2015 - 01:11 PM
I was just wondering if the BSA (Body Surface Area) which is a way to translate dosage from animal to humans can be applied here for Quercetin. Using the conversion for mice given HERE, your 50 mg/kg dose for 70 kg would be much lower, i.e. 3500 mg x 3/37 = 284 mg I think. But there is the problem of pharmacokinetics of absorption though. Can someone enlight this point?
I wish someone could enlighten us. The HED conversion has been a long-standing area of concern. I worry a lot about differences in xenobiotic metabolism between humans and mice causing errors here. I think dasatinib is less of a problem, because it was designed to avoid xenobiotic metabolism. Quercetin, on the other hand, is very heavily metabolized. It's a sufficiently benign compound that I'd be inclined to use a larger dose than the HED predicts, but the only way to really know what's right is a dose-ranging experiment. We would need to have a ton of people randomized to different doses, and do before/after biopsies and a lot of other tests. If enough people do n=1 experiments on themselves, it might be possible for real effects to emerge, but placebo effects are going to be a big problem.
Posted 21 March 2015 - 02:05 PM
Just took the remaining 75mg with a little bit of grapefruit juice (increases serum levels) and 1600mg of Quercetin.
Cosmicalstorm is right: taking drugs with grapefruit juice is generally a bad idea, especially unfamiliar ones. But apparently you're aware of the reason, and one extremely brave guy. So thanks for that! Can you please provide more details on your predosing physical and mental health, and the acute effects of the therapy thus far?
Posted 21 March 2015 - 02:23 PM
Just took the remaining 75mg with a little bit of grapefruit juice (increases serum levels) and 1600mg of Quercetin.
Cosmicalstorm is right: taking drugs with grapefruit juice is generally a bad idea, especially unfamiliar ones. But apparently you're aware of the reason, and one extremely brave guy. So thanks for that! Can you please provide more details on your predosing physical and mental health, and the acute effects of the therapy thus far?
There aren't any real effects to report yet. I feel groggy and fuzzy but slept decently last night. I only had that remaining 75mg and *someone* recommended boosting it with grapefruit juice which based on dosage could have between a 1.5 - 2x effect in theory.
Posted 21 March 2015 - 03:58 PM
As for an hypothesis. Let's for the arguments sake assume that most cells can only divide about 50 times before their telomeres get so short they are no longer able to replicate. If you kill of all senescent cells as well as the "soon-to-be senescent but working quite well at the moment" cells, the remaining cells are likely to start replicate faster, taking the recently died off cells places. The first times you kill off these older cells you are likely to get organs and a body which work better because all the old cells have been eliminated. However, for each time you repeat the process, the remaining cells will get shorter telomeres and will themselves get closer to the point where they will no longer be able to work or replicate. My hypothesis is that if you repeat this process too many times, your cells will age rapidly to the point where most of the cells will go into apoptosis, making the organs they are part of to fail. You should be able to test this hypothesis by repeatedly administrating the drugs on people which are not suffering from accelerated aging. I expect the results to be people with greater average health span but with shorter average life span.
It's not that simple.
Some stem cells can keep their telomere length completely flatlined throughout your life, if we use telomeres as a measure of aging, your muscles never truly age. Their stem cells are just as capable of replacing muscle in your 80s as they are in your 20s - of course disregarding the fact that they can't because it's their environment that has changed. No correlation has been found between satellite cell viability, quantity and age related muscle wasting - and believe me (or check pubmed
Senescent cells can force other cells into senescence long before they've reached their Hayflick limit. In a way by simply being in a tissue the senescent cells already do what you fear removing them will accomplish. And much faster.
Mathematically the first organ capable of reaching the Hayflick limit in your body is the thymus. At age 125. No one has reached even close to that age so we can't know if it's a real possibility for all cells of an organ to go into senescence. And even if it happens, well, there's always transplantation.
Most people die from pathologies caused by chronic inflammation and impaired cellular turnover, so removing senescent cells gives the people who were going to die in their 60s and 70s from a CVD or cancer a bit of extra time - or maybe a lot of extra time, we'll see.
It's very straightforward, I'd even say it's in line with the mainstream medical thinking - which is good, it will be incorporated into medicine faster than most other proposed anti aging therapies.
Yes, I know it's not quite that simple. It's the underlying principles for several organs in the body I want to illustrate. Without a speed up of cell divisions the Hayflick limit for these organs might be reached at a certain age, with a speed up of cell divisions it's likely to be reached at a lower age.
Removing old non-working cells by triggering apoptosis in them might give you a longer health span, might even give you a somewhat longer lifespan, but I'm not sure it will work as a long term strategy to fight aging. That is, trying to reach an age of several hundred years or so.
But if you could combine the strategy of killing of senescent non-working cells with a working strategy to extend telomeres in working cells, that would be very interesting.
Posted 21 March 2015 - 04:21 PM
As for an hypothesis. Let's for the arguments sake assume that most cells can only divide about 50 times before their telomeres get so short they are no longer able to replicate. If you kill of all senescent cells as well as the "soon-to-be senescent but working quite well at the moment" cells, the remaining cells are likely to start replicate faster, taking the recently died off cells places. The first times you kill off these older cells you are likely to get organs and a body which work better because all the old cells have been eliminated. However, for each time you repeat the process, the remaining cells will get shorter telomeres and will themselves get closer to the point where they will no longer be able to work or replicate. My hypothesis is that if you repeat this process too many times, your cells will age rapidly to the point where most of the cells will go into apoptosis, making the organs they are part of to fail. You should be able to test this hypothesis by repeatedly administrating the drugs on people which are not suffering from accelerated aging. I expect the results to be people with greater average health span but with shorter average life span.
It's not that simple.
Some stem cells can keep their telomere length completely flatlined throughout your life, if we use telomeres as a measure of aging, your muscles never truly age. Their stem cells are just as capable of replacing muscle in your 80s as they are in your 20s - of course disregarding the fact that they can't because it's their environment that has changed. No correlation has been found between satellite cell viability, quantity and age related muscle wasting - and believe me (or check pubmed
Senescent cells can force other cells into senescence long before they've reached their Hayflick limit. In a way by simply being in a tissue the senescent cells already do what you fear removing them will accomplish. And much faster.
Mathematically the first organ capable of reaching the Hayflick limit in your body is the thymus. At age 125. No one has reached even close to that age so we can't know if it's a real possibility for all cells of an organ to go into senescence. And even if it happens, well, there's always transplantation.
Most people die from pathologies caused by chronic inflammation and impaired cellular turnover, so removing senescent cells gives the people who were going to die in their 60s and 70s from a CVD or cancer a bit of extra time - or maybe a lot of extra time, we'll see.
It's very straightforward, I'd even say it's in line with the mainstream medical thinking - which is good, it will be incorporated into medicine faster than most other proposed anti aging therapies.
Yes, I know it's not quite that simple. It's the underlying principles for several organs in the body I want to illustrate. Without a speed up of cell divisions the Hayflick limit for these organs might be reached at a certain age, with a speed up of cell divisions it's likely to be reached at a lower age.
Removing old non-working cells by triggering apoptosis in them might give you a longer health span, might even give you a somewhat longer lifespan, but I'm not sure it will work as a long term strategy to fight aging. That is, trying to reach an age of several hundred years or so.
But if you could combine the strategy of killing of senescent non-working cells with a working strategy to extend telomeres in working cells, that would be very interesting.
Has anyone proposed that we are going to reach centuries by removing senescent cells? I seriously don't think it will do much at all. A decrease in the risk of certain chronic disease would be nice.
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