This is a letter I wrote to a dear friend from the 1970s who has been diagnosed recently with colon cancer. She had surgery last summer to remove the primary tumor, and is in the midst of a 12-week course of chemotherapy. She has, in my opinion, a well-balanced view of the relative merits of traditional vs alternative treatments. One unusual thing about her situation is that she has an extraordinary social support system, having led a community of peer counselors within the disability community for many years, and now benefiting personally from the community of people she has helped.
Dear M—-,
We would like to be able to derive from the research on controlled clinical trials a “best bet” treatment option, but the data to support this inference don’t exist. One reason is that only chemotherapy has been tested with controlled clinical trials, and for your particular brand of cancer, the odds that chemo offers don’t look attractive. For alternative treatment modalities, we have only anecdotes and not controlled trials. Another reason is that cancer is an individual disease, more so than heart disease or infectious diseases. Different people respond very differently, and the medical community has not yet figured out how to tell in advance which treatments will work for which patients.
Western medicine profoundly misunderstands the nature of cancer. The classical understanding is that cancer results from a series of random mutations as the body’s stem cells divide, culminating in some combination of genetic abnormalities that enable a single cell to evade apoptosis and all the body’s defenses against cancer. In this paradigm, the root of the problem is in the DNA of the cell nucleus. But we know from experiment this is not true. When the DNA-nucleus of a cancer cell is transplanted into a normal cell, the normal cell remains normal, and when the DNA-nucleus of a normal cell is transplanted into a cancer cell, the cell remains cancerous [ref, ref]. I don’t pretend to understand the true cause of cancer, but I suspect it is related to the mitochondria at the cellular level, and to immune and other deficiencies at the system level that make the metabolism as a whole hospitable to cancer.
When our bodies are healthy, cancer is nipped in the bud, probably as a frequent and routine occurrence. Cancerous cells are induced to commit suicide (apoptosis) or they are marked out by the immune system and destroyed by white blood cells. Cancer arises as a clinical reality only when the body fails to do this. Western medicine makes the mistake of focusing exclusively on killing the cancer, without attention to re-balancing the body or strengthening the immune system so cancer cannot recur. In fact, chemo and radiation both damage the immune system, which you depend on to guard against a recurrence.
I’ve heard some doctors say, and I believe it’s true, that all cancer treatment modalities rely in the end on your immune system to kill the last few cancer cells and to prevent recurrence. When cancer recurs, is it because just one cancer cell managed to survive the onslaught of chemo, or is it because the immune system is so weak that the body is highly vulnerable to new instances? It is an academic question, because in any case we need a healthy immune system to survive.
At some point, our plan will be to switch over from killing the cancer to healing your body and restoring your immune system. Maybe we’re already at that point, after surgery + four chemo infusions. Maybe you’re ready now to make the transition. Cancer-killing treatments make you feel bad, accelerate aging, and damage your body. In contrast, healing and immune support will feel good in the present and will have beneficial side-effects for other aspects of your health.
There are many credible alternative cancer treatments out there. None of them is a universal cure, but all of them have worked for some significant percentage of people who tried them. The plan will be to choose an alternative clinic or a medication or a diet plan and try it for about 6 weeks. The proposal depends critically on having a sensitive and non-harmful test that you can do every 6 weeks for feedback on whether the treatment is working.
My proposal will take time. I believe you have time. You’re not going to die this year or next year, and we have time to try at least a dozen treatments. We don’t expect the first one or the second to work, but there’s a good chance one of them will. There are many, many stories of people who have banished cancer from their bodies. You’re the next success story, waiting to be told.
I propose that you tell your oncologist that you want to find out if the 4 doses of chemo have killed the great majority of the cancer, so that you can now strengthen your own system to handle the last few (chemo-resistant) cells. Tell her that you are open to returning to chemo in the future should it be necessary, but that for the next phase, you want to try a series of alternative treatments that are non-toxic and have only beneficial side-effects. Each of these has worked for some fraction of patients, and your expectation is that one of them will work for you. Tell her that you would like to ask her to work with you as an expert diagnostician, using blood tests and subjective state of health to tell when a treatment is not working, so you can move to the next option, and to tell you when a treatment is working, so you can stick with it.
(I believe PET scans are the most informative test for cancer, but your oncologist will know much more than I. PET scans are expensive, and I imagine that insurers discourage their overuse. More concerning is that the radiation dose is about 100 times a chest x-ray [ref], so we’ll be counting on your oncologist to come up with a less damaging battery of tests that you can do, perhaps as often as every 6 weeks.)
We have lots of candidate treatments to try, from the Moss Report, from the Polizzi video or a long list of herbal medicines, from your sources and mine. There are approaches that involve killing cancer cells with medicines that are much less toxic to your non-cancerous cells, for example, intravenous vitamin C, curcumin, cannabis, dichloracetate, and many others. A complementary approach strengthens the body’s resistance to cancer, especially the immune system. In the end, it must be your own healthy immune system that protects you from cancer. Reishi and other mushroom extracts, Cimetidine=Tagamet, Nigella sativa (kalonji seed), spirulina, and green tea extract are among many nutracuticals that strengthen the body’s resistance to cancer. I want to remind you especially of the research of Valter Longo, a USC professor who has worked with fasting and diets that discourage cancer. There are alternative cancer clinics in Canada and Mexico and around the world that have cured some fraction of the people who have sought their help.
Almost all of these interventions have been attacked or dismissed as frauds. Sometimes this is because they really are frauds, and sometimes it is the medical community circling its wagons to avoid infiltration by researchers outside the mainstream. Until we look in detail at the accusations and the results, it is difficult to tell the difference, and even then we’re often left guessing. Much of the debunking is based on theory–“there is no credible biochemical mechanism by which xyz can cure cancer.” I take these pronouncements with a grain of salt, and look only at the empirical results. We don’t understand cancer well enough to dismiss anything on theoretical grounds
Any one of these options has a low probability of providing deliverance from your cancer, but you have time to try 10 or 20 of them, and there is a very good chance that you will respond to one of them. You are destined to become the next “miracle cure” cancer anecdote — we just don’t know yet which one you will be.
I’ve mentioned to you a fallback option, in the unlikely event we should find ourselves two or three years from now with a persistent, active threat of cancer. The last resort would be to replace your immune system with a bone marrow transplant from your niece (or another related donor, preferably younger). The upside is that the transplanted immune system absolutely will not tolerate your cancer, and will eliminate it promptly. The downside is that you expose yourself to “graft-vs-host disease”, in which your immune system also treats healthy cells as “foreign” and attacks them. This is a potentially fatal complication, and would probably consign you to immune suppressants for the rest of your life.
I’m in this with you for as long as it takes. So are your dear friends and family and the deep community of people who are full of gratitude for the years of love and attention you have offered them.
— Josh
Discussion
156 reader comments
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This is why I have very significant fatigue and reduced exercise capacity with metformin https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12880
Thank you for the link.
This validates the self-observed negative affects on exercise capacity reported to me by a handful of people using a similar dosages of Metformin for anti-aging self experimentation.
"Slowing Aging Using Drug Synergy" Optimum combinations of rifampicin, rapamycin, metformin, allantoin, and psora-4 were investigated to extend the lifespan of C-elegans.
https://www.biorxiv.org/content/biorxiv/early/2017/06/21/153205.full.pdf
Best combination was rifampicin 50 uM plus rapamycin 100 uM which nearly doubled lifespan.
They found metformin was "poisonous" when combined with rifampicin, lowering the lifespan achieved with rifampicin alone.
They found the optimum dose of metformin combined with rapamycin was only 25 mM (and rapamycin at 50 mM). Higher concentrations of metformin gave lower lifespan.
Rifampicin appears to be a ROCK inhibitor.
Kaplan Medical ... Termination of transcription sometimes requires a protein called rho (ρ) factor. The prokaryotic RNA polymerase is inhibited by rifampin.
ROCK inhibition combined with Rapamycin benefits are seen with Balogskonny on using statins with Rapamcyin as well as the study Robert posted showing benefits of Rapamycin, Rifampicin, and Allatonin.
This is an exciting study showing the capacity of mTOR and ROCK kinase inhibitors to de differentiate glioblastoma cells into normal neurons. Good news for rapamycin users!
https://www.ncbi.nlm.nih.gov/pubmed/30071868
Anyone know what a ROCK kinase inhibitor is?
ROCK inhibitors are precisely what I have been researching for rejuvenation (as part of my cyclical statin-sartan protocol). Turns out that they aid in the conditional reprogramming of normal cells into progenitor-like cells when combined with senescent feeder cells. Direct ROCK inhibitors aren't generally available, but statins have been shown to have this effect over time, which probably explains their benefits on endothelial cells and also their long term side effects (blocking of stem cell differentiation).
https://www.ncbi.nlm.nih.gov/pubmed/22189618
Interesting that the combination with mTOR inhibition produces another distinct but no doubt related effect.
For a natural rho kinase (ROCK) inhibitor check out Reishi mushroom extract.
That’s interesting Robert. Any idea of dose?
None.
But I've been taking a 1/2 tsp of 100:1 Reishi root extract b.i.d. along with 4mg of candesartan b.i.d. just in case it improves my endothelium. (Not that I know of anything wrong). The reishi extract is a substitute for Fluvastatin which is presumed to work via rho-kinase inhibition in the study below.
"A Low-Dose Combination of Fluvastatin and Valsartan: A New “Drug” and a New Approach for Decreasing the Arterial Age" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363554/
Good to see someone else has picked up on Janic's work Robert. I've tried his one month protocol and experienced benefits. Any particular reason you don't want to use a statin?
Statins are known to have all sorts of negative effects on muscle in SOME users when a particular gene known as Atrogin 1 turns on and begins muscle breakdown.
In some users the muscle weakness and muscle breakdown and other issues are quite obvious.
Rhabdomyolysis can be deadly.
The heart is a muscle.
The breakdown of muscle is associated with illnesses such as cancer, sepsis, and AIDS.
So if that Atrogin 1 gene is activated statins should not be used.
Well in all the studies by Janic et al. the treatment was at a very low dose (10mg statin) and only for 1 month, so probably no need to worry about side effects. In fact he discovered that a low dose and a limited time protocol was MORE effective for the pleitrophic effects he was after (arterial rejuvenation). And if you are still worried - Q10 can be supplemented at the same time and according to my research should not impact on the effectiveness of the treatment. It is also my view (opinion rather than established fact) that the side effects of Statins are likely down to a bias in stem cell division preventing proper differentiation - which is useful for increasing progenitors, but if continued too long will harm the body because of the constant requirement for differentiated cells.
https://www.researchgate.net/publication/280496460_Low-dose_fluvastatin_and_valsartan_rejuvenate_the_arterial_wall_through_telomerase_activity_increase_in_the_middle-aged_men
It's really quite remarkable work although some more work is required to fully explain the effects - mainly about how the ROCK inhibition either creates or sets free endothelial progenitor cells. For me the only downside is that the arterial rejuvenation (also likely by virtue of the bloodstream to help other organs), which is on the order of 10 years(!), only lasts around 6 months before the aging phenotype reasserts itself. The treatment can be repeated successfully, but still - perhaps Akshay can shed light on the signalling in the bloodstream that has this unfortunate effect?
Mark my thoughts are that various damage occurs due to deliberate down regulation of repair systems. When we can find a safe agonist of any of the repair systems it will mitigate the damage outcome of that pathway and will continue to do so until at some point it is overwhelmed by interconnected rising cascade of other outcomes of damage. But one must not miss an opportunity to benefit till then. I myself take 5mg atorvastatin 4 times a week even if my cholesterol levels are considered by doctors in safe zone.
On the over all boost one can get by the hormetics I believe that when it doubt go with Paul. I stopped my brief experiment with metformin 500mg and switched back to rapamycin 3mg once a week. One more study came out concluding that metformin negatively impacted capacity to exercise.
Hi Mark
That's a fascinating article and pretty amazing actually. Valsartin is hard to get at the moment due to a massive recall due to contaminants ( NMDA) or something. I now think that if your arteries are presently pretty clear that it may be possible to prevent coronary artery disease almost entirely and perhaps indefinitely with
1. K2 and magnesium
2. Pine Bark Extract and Goyu Kola
3. Once every 6-10 months of low dose fluvastatin with valsartin
4. rapamycin
It seems that the endothelial benefits of the third approach is linked to significant telomerase activation. This will raise the debate of trade off once again, CAD vs. cancer due to telomerase and longer telomeres. As you know, I believe that critically short telomeres are DNA destabilizing and are much more of a cancer risk than long ones, but the objection will be raised.
Thanks Akshay and Paul for your ideas.
I think that it's likely some extra endothelial cells are formed because of the statin-sartin combination and this is the source of the extra telomerase and NO, etc. I don't understand why treating for longer or at a higher dose gives a worse outcome, as ROCK inhibition will be greater with a larger statin dose. There must be some sort of complex, negative feedback loop.
After treatment has ceased the normal growth signals will probably cause the extra progenitor cells to differentiate and the benefits will gradually be lost. So this is as expected.
I wonder if a prior senolytics course might change the signalling so that the benefits would last longer? After all young people take a while to get old!
I agree with you Paul that telomerase is as Michael Fossel's says, 'permissive of cancer, but not causal'. But we do know the glitazones (PPAR activation) are linked to bladder cancer - I believe there may be a similar mechanism of action at work here, and increasing the migration ability of progenitor cells might be cancer permissive too in the long run if other things are lined up (such as poor metabolic health).
Mark:
Unfortunately the side effects of pharmacuetical drugs do not rear their ugly heads until it is too late, far too often.
IMO, even a small intermittent dosages of statins can cause damaging epigenetic gene changes.
But, if you are happy using statins, go for it.
I have lowered Cholesterol in many people, totally without drugs, only nutritional and lifestyle changes.
There is a small subset who may need the statin. Perhaps you are one.
It that case it's a risk benefit decision.
Cholesterol reduction is irrelevant - it's ROCK inhibition I'm after. Hence the idea of short term, low dose statins. It's the pleiotropic effects that may prove anti aging.
The "Hasini" protocol to inhibit IL-6 to stop cancer from metastasizing uses a combination of two FDA approved pharmaceuticals.
The inexpensive and non-toxic polypodium leucotomos extract sold as "Heliocare" has been reported to suppress IL-6 very well in vitro. "Surprisingly, the production of the inflammatory cytokine IL-6 was completely abolished (100% inhibition) by PLE at all doses tested." Also known as "Fernblock" this fern extract prevents sunburn and inflammation. (perhaps by IL-6 suppression). https://www.ncbi.nlm.nih.gov/pubmed/10928072
There is much to consider here Adrian.
First of all, both groups, those with long and those with short telomeres achieved longevity, but the distinction of course was in regards to overall health and functionality. The group with the longest T cell telomere lengths and telomerase activity were clearly healthier. This coincides with the prevalent notion that immune functioning is of enormous importance and immunosenescence is a big problem. But questions remain.
Does telomerase advance the epigenetic clock? Do long telomeres correlate nicely with a long and highly functional life, but not to advancing maximal longevity?
Would it be optimal to combine an mTOR inhibitor to a telomerase stimulator, but not continuously, but rather in a pulsed manner, like monthly?
Maybe add in some T cell activators like modified rice bran, Cistanche, pue-rh tea, Reishi, etc., also cyclically?
Still much to learn.
Here’s a fascinating study of centenarians, and in particular the very healthiest subgroup, focusing on the importance of T cells, T cell telomerase activity and telomere length, and how these relate to high levels of function in the very old. They also discuss the role of chronic inflammation and IL 10 levels.
I’m now cycling in four supplements to help with T cell activation.
https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12859
Hi Paul, which four would that be?
Many thanks Paul for bringing it up.
There's also a very interesting discussion on the Telomere position effect over long distances. This study and the latest Horvath epi. clock I posted above, which shows a correlation between cell divisions and DNAm age, have rekindled my interest in telomeres.
This is the case that Michael Fossel has been making for many years. In particular when it came to explain progeria, the effects we see would be the result of excessive cell proliferation, as cells affected by the defective protein that causes the disease commit apoptosis and others proliferate to take their place at a higher rate than in healthy individuals.
Perhaps we have been a bit too hasty to dismiss telomere attrition as a principal cause of ageing.
You're right. Many HAVE been too hasty to dismiss telomere attrition as a primary cause of aging.
Think of it this way. It's very simple. Any damage, be that ROS from mitochondria, invasion by viruses, impact damage from sports, mutations from smoking, whatever - cells will die and others will have to divide more to replace them. Hence lifestyle factors and genetic predispositions and plain old luck lead to the exact patten of aging in different tissues in different individuals, but aging will always occur eventually if for no other reason than shortening telomeres and altered (read impaired) gene expression, which makes it more difficult for cells to make further replacements in the face of damage.
Cancer makes immortal cells. It regenerates telomeres by generating telomerase. So telomere length is not finite. What we lose with aging is our ability maintain it's length. That makes it an outcome in a cascade wherein it causes loss of cell viability. If one takes another example of thymus one can show it as a cause of aging by the same logic. As it shrinks immune function begins to get affected. Immune dysfunctions lead to chronic inflammation which in turn leads to most of the diseases associated with aging. But that's not the case. The program that shrinks the thymus from the time we are born also reduces our telomerase. There is a program that dials down our ability to repair and regenerate.
I never said it was finite. Cells clearly can re-extend their telomeres; this has been demonstrated many times, many different ways in the lab.
The question is why this doesn't happen in grown humans.
I think it is probably built in as a way of shifting cancer risk from the young to the old. Others, yourself and Josh included believe it's the downstream consequence of a more fundamental program.
Either way should be amiable to intervention and the reversing of aging. And I don't care which turns out to be true, so long as the problem is solved!
Hi Akshay.
Just had my mind blown by this paper.
https://elifesciences.org/articles/17915#abstract
Its a study profiling gene expression changes in the brain in the mid-twenties being very important to the onset of schizophrenia.
In my view this strongly supports your assertion of programmed changes in gene expression leading to down regulation of maintenance pathways.
Of course the paper does not explain what the trigger for such gene changes is, other than it being part of development and possibly related to methylation changes.
Looking forward to seeing what buttons you and Harold have learned to press to restore youthful gene expression!
I have recently been experimenting with ways to increase progenitor cells and also the clearance of old cells. I've found evidence that the two processes can be synergistic. Will beat this thing!
Akshay, it all sounds very encouraging, and I wish you the best of success. I hope the pill won't be just another antioxidant-pill, ramping up Nrf2, downregulating NF-Kb and so on.
We have plenty of mitchondrial "renewal-kits" on the market, which do little to nothing.
What annoys me most about aging is the loss of flexibility in muscles, morning stiffness in tendons/joints and of course decreased ATP production in muscle mitochondria. In my 30's I could jump right out of bed and run 5miles without warming up. This is long over.....
IMO, one of the overlooked hurdles in aging is the build up of crosslinked proteins in the extracellular matrix. Currently, we have no way of getting rid of this extracellular garbage. Senolytics is of no use. Epigentic rollback won't help us either.
To my knowledge there is no SAFE way to reverse crosslinked proteins. Additonally, a method that would address the destruction of about 20 different types of known crosslinks seems like an overwhelming task.
I'm curious what 4 supplements are you cycling and how often
For 3 consecutive days every other week some combination of
Andrographis
NK cell activator
Reishi extract
Astralagus as TA 65
Cistanche
Puerh tea
This is a study out of Yale on very long lived tortoises. They have the genetic ability to suppress cancer, repair DNA, and maintain their immune system.
https://www.sciencedaily.com/releases/2018/12/181203115438.htm
It’s interesting that the naked mole rat also has those innate abilities.
As far as I know, only rapamycin and CR come close to replicating it, though curcumin may be a fairly close 2 nd.
Paul
Interesting article. Thank you for the link.
Re. the Horvath clock, I wonder if anybody else missed out on this July'18 study that published a new clock, specifically developed to measure DNAm age in skin and blood tissue.
https://www.aging-us.com/article/101508/text
They can now detect an increased DNAm age in progeria patients and a wider correlation between cell proliferation (doubling) and DNAm age. They can also better plot fibroblast methylation age to the chronological one whereas the previous pan-tissue clock would make them appear older than other tissues (they still could be, according to other measures).
Very important insights in my opinion. Previously, we could only link DNAm age to metabolic processes, to account for the apparent constant rate of ageing observed in non proliferating tissues and the fact that some cells in culture didn't seem to increase their DNAm age with cell doublings.
So could it be that DNAm age is correlated to cell proliferation after all?
OT for this thread, but I look forward to Josh and others commenting on the latest senolytic discovery ( Azithromycin, FDA approved and generic) — very selective activity seems promising. Obviously more study will be required.
https://www.researchgate.net/profile/Bela_Ozsvari/publication/328948748_Azithromycin_and_Roxithromycin_define_a_new_family_of_senolytic_drugs_that_target_senescent_human_fibroblasts/links/5bfd33dea6fdcc35428b7dba/Azithromycin-and-Roxithromycin-define-a-new-family-of-senolytic-drugs-that-target-senescent-human-fibroblasts.pdf?origin=publication_detail
Josh
While we're on the subject of cancer - any chance of getting Thomas Seyfried to contribute to a post? Just been reading his 2017 paper, which is very convincing on the metabolic origins of cancer (which I know you've mentioned before).
https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-017-0178-2
So rapamycin leads to a younger epigenetic age whereas anti-hypertensives are aging, at least according to a recent study showing that all BP meds lead to an older epigenetic profile.
This presents a real conundrum to a practicing physician such as myself where, over the long term , the cure may be worse than the disease. Even worse, the cutoff for treating hypertension has become even stricter. This is almost a holy grail of the medical community so refusing to treat HBP for almost any reason would be seen as a severe violation of standard of practice.
My own experience has shown me that very few things actually make me feel younger. These include rapamycin, pine bark extract, exercise, and perhaps melatonin. On the other hand, when I tried the ACE inhibitor lisinopril, I literally felt older, so I think there may be something to this study, but it surprises me that it pertained to all BP interventions.
I wouldn't get too hung up on Horvath's clock Paul.
Anti hypertensives don't make you older (your own experience with ACE inhibitors not withstanding). They just make certain cells in the artery wall live longer. Hence they have more time to acquire epigenetic variations.
This is the same reason those with longer telomeres appear to have an older epigenetic age: they cells need replacing less often from the (epigenetically younger) stem cell pool.
Incidentally sartans activate telomerase in endothelial cells. Win win as far as I can tell.
That makes sense, but then I would assume that under the influence of rapamycin, which slows cellular proliferation, that they too would be replaced less often and would have an older epigenetic age, but that is not the case.
On the other hand, rapamycin tilts the anabolic/ catabolic balance towards the catabolic and that would indeed cause those cells to be replaced with younger ones and a younger epigenetic age would be the result. This effect may actually be real.
Rapamycin might make cells live longer, I don't know. But it also suppresses inflammation and probably reduces many growth and metabolic signals. This probably accounts for slower methylation changes.
Paul
You wrote: [ "On the other hand, rapamycin tilts the anabolic/ catabolic balance towards the catabolic " ]
Well, that is why it may be crucial to get the dosage correct because what if a too high dose pushes one too far toward the catabolic state.
One issue with older folk is inability to hold onto muscle and weight loss in general.
Rapamycin does cause weight loss. But the balance may be crucial
Cigarettes cause weight loss, too.
Heather
David Sabatini, an expert in all things mTOR, believes that catabolic breakdown, followed by rejuvenation by younger and healthier tissues, is the reason for the subjective improvements that many of us experience after just a couple of months on rapamycin.
It would also explain the objective increase in cardiac ejection fractions which is evidenced in the recent dog studies.
To me this suggests Paul, that you might only need to take rapamycin for a couple of months every X years.
Fits with my subjective experiences of being on rapamycin for almost 2 years, then doing it only 1/month, then going back on it weekly, then coming off it for a protracted period. Although I felt the improvements you describe in the first 6 months, it now doesn't seem to make.any difference whether I'm on or off it (age 40), and I still feel as good.
Dogs age 8 times faster, so that 4 years for a human to return to baseline.
Hi Paul:
I honestly did not feel any subjective improvements on Rapamycin. None.
Perhaps because I have been for a long time taking natural substances that block the mTORC1 pathway and had no health issues to correct.
Also, I am tending to think Mark may be on to something in that Rapamycin may only be needed ever X number of years to perform the mentioned effect of catabolic breakdown followed by rejuvenation.
I am not arguing the effect, only the method of getting there.
Even the natural mTOR inhibitors may only be needed cyclically. ...stopped for two years after being taken for a few months.
Like Mark, I feel no difference since stopping the Rapamycin, but again, that may be because I had no health issues that needed correcting.
Perhaps if some one has decreased cardiac injection fraction, either diagnosed or undiagnosed, or a weaker immune system, and the rapamycin is used, then they would feel a difference and it would be measurable.
What does it do in a healthy person, though?
Could it throw off balance in a negative way?
Many people who take an anti aging drug/supplement or lifestyle intervention expect an instantaneous effect. But in my opinion aging is very slow in humans. Yes you can tell the difference between even a 20 and 30 year old, but our interventions are as yet very crude. Almost miraculous results may occur with very old animals (or humans) taking rapamycin. But others (often younger) experience nothing.
Until we have a real and accurate way to assess the process of aging (which is more accurate than just looking to someone), we will have these difficulties in assessing efficacy. Or until we have such an effective remedy for aging that there is no doubt.
That's just why I'm promoting the DNA methylation clock.
Paul:
You wrote: [ "I had a 25%drop in my insulin levels, a 15 lb. weight loss, and a 10% drop in my white count. Also had a significant increase in endurance and overall well being." ]
That is excellent Paul.
I think perhaps I felt no change because I have been taking nutrients and herbs for years, some of which offer similar benefit to Rapamycin, therefore all of my similar parameters were already in range.
Also, I was already slim and exercise vigorously daily.
So, Perhaps Rapamycin does slow aging, but it will not be obvious in a person that has no measurable health issues to address.
Or, it could be, as the studies show, that women do not respond the same way men respond.
Mark:
You wrote: ["Almost miraculous results may occur with very old animals (or humans) taking rapamycin. But others (often younger) experience nothing. "]
I agree. So then the question of risk vs benefit arises.
I may revisit Rapamycin at a later date, or even after some of the dog studies are completed.
But for now, I am taking a break.
However, if I was seeing the improvements Paul is seeing, I would continue with Rapamycin.
Great if it works Josh. From what I've seen so far from my reading of Horvath's papers, and the results at Longecity using related clocks - I think it's got a way to go.
Hi Paul. Almost certainly we are talking about mtROS. That seems to be the main source of nuclear DNA damage and cellular arrest.
MitoQ might help. As might other electron acceptors like methylene blue. Such long terms studies have never been done on humans and cancer rates, though I have read good things about mitoQ and metastasis prevention.
https://www.sciencedirect.com/science/article/pii/S2211124714005270
Thanks for the clarification Akshay. Intriguing about the two edged sword of inflammation.
Hi Mark,
Replication, rather than ROS, seems to be the main source of mutation in humans. Men's germ cells undergo about 400 replications per generation while women's only about 30. As a result men's germ cells harbor 10 times as many mutations by the age of 30, with very little increase in total mutations during the fertile lives of women.
Somatic mutation rate seems to be higher by most accounts. Perhaps female eggs are under a certain state of quiescence that allows them to preserve their genome integrity better than other tissues. But some level of maintenance activity must still go on.
You can find a nice chart of the mutation rate over at Laurence Moran's blog 'the Sandwalk':
https://sandwalk.blogspot.com/2017/11/parental-age-and-human-mutation-rate.html
ROS may be a major cause of DNA damage and a trigger of a DNA damage response that leads to cell arrest, senescence or apoptosis. But metabolism alone seems to be a minor source of mutation.
Although these levels are appreciable, from 1 to 10 mutations per cell division depending on the source (and the tissue), I am skeptical that mutation alone is the trigger of cancer. Perhaps in fast proliferating tissues is more of a factor, but in most somatic cells the levels seem to be similar to inter-generational mutation rates.
To me, there clearly needs to be another process underlying it. Most cancers exhibit behaviour we only see in stem cells, so I would say they originate in that state and the failure to control its proliferation. We know that this process is largely driven by epigenetic control so it makes sense something similar is going on in cancer.
I think that one of the reasons we have traditionally regarded cancer as mainly driven by mutation is because we are assuming they accumulate to disruptive levels as we age. But this does not seem to be the case. Personally, I think it is the down-regulation of the immune system that results in the higher incidence with age.
I agree that in the short term this does not lead to any practical application, but long term I hope that's not the case. We have only just discovered iPSC cells and OSKM factors, much is left to research.
Hi Adrian,
Yes we discussed this upthread and I posted a paper which modelled cancer incidence based on immune decline with a small number of mutations, rather than the larger number traditionally required. So I agree cancer is not primarily caused by mutations but by the loss of the ability to nip them in the bud that leads to cancer. It may well also be that a young cellular environment also exerts a level of epigenetic control beyond immune signalling.
As for aging, this is somewhat different as it is not caused by mutations, but by the amount of cellular arrest caused by (primarily) ROS, and the requirement to replace such losses, which ultimately can lead to proliferative exhaustion, if the consequent senescence and inflammation does not get us first.
Here is a report for a cure for pancreatic cancer, which is almost always deadly and "incurable" as of conventional medicine. It is in German but many - I guess - can read and understand it. Google translate will help if needed.
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Bauchspeicheldrüsenkrebs – wieder einmal besiegt
Eine der dramatischsten Krebsformen ist das Karzinom der Bauchspeicheldrüse. Fulminanter Verlauf. Nur sehr kurze Lebenserwartung. Der Patient wird quitte-gelb, isst nichts mehr, magert rapide ab, hat grausige Schmerzen. Oft verbunden mit Lebermetastasen, nicht operabel. Bleibt eigentlich nur Morphium.
Wenn man solch einen Patienten trotz aller Voraussagen am Leben erhält, es ihm gut geht, er also beschwerdefrei ist und wenn der Krebs samt Metastasen Jahr für Jahr kleiner wird... dann berichtet ein Arzt darüber. Auch wenn ihm dieser Bericht um die Ohren gehauen wird aus dem einfachen Grund:
Das Wunder heißt Vitamin C. Wieder einmal.
Es genügen wenige Worte. Mann. 68 Jahre. Großer Bauchspeicheldrüsenkrebs, Leber voller Metastasen. Lehnt jegliche Behandlung ab. Operation sowieso nicht möglich, aber eben keine Chemotherapie, keine Bestrahlung.
Kommt vor. Gibt es. Der Mensch hat mit seinem Leben abgeschlossen. Will die letzten Tage durch Chemotherapie nicht noch unerträglicher machen. Alles verständlich.
Der Patient bekam zwei bis drei Mal wöchentlich
Vitamin C 75 -125g als Infusion.
In der veröffentlichen Arbeit sehen wir ganz anschaulich jährliche Kontroll-PET-CT´s und sehen, wie der Krebs kleiner wird, wie Metastasen verschwinden.
Entscheidend: der Patient verlor kein Gewicht mehr, hatte keine Schmerzen. Also fast Idealzustand trotz dieser Zeitbombe im Bauch.
Weshalb er dann nach vier Jahren gestorben ist? Nun ja... Schulmedizin. Man hat ihm auf Verdacht einen Stent, ein Röhrchen in den Gallengang geschoben. Zum besseren Abfluss. Zwei Wochen später septischer Schock. Notfall. Das Röhrchen war gewandert und hat den Darm durchlöchert. Das war´s dann.
Quelle: ANTI-CANCER DRUGS 2018 Apr; 29 (4): 373
Das Geheimnis dahinter ist selbstverständlich kein Geheimnis. Wurde uns schon 2005 erklärt von Wissenschaftlern des NIH, also der größten und wichtigsten Forschungseinrichtung dieses Globus.
Als sie zeigten, dass man mit Wasserstoffperoxid Zellen töten kann. Besser gesagt: Krebszellen. Und dass eine Vitamin C – Infusion genau dieses Wasserstoffperoxid (H₂O₂) produziert, Krebszellen tötet. Umliegende gesunde Zellen aber in Ruhe lässt.
Schon einmal hatte ich Sie gefragt, wie man es schaffen könnte, genügend Vitamin C genau an die Krebsnester hinzuschaffen. Korinthenkacker und Klugsch... halten das natürlich für nicht möglich. Nun ja, vielleicht haben sie Recht.
Haben sie natürlich nicht. Siehe oben. Zwei bis drei Mal die Woche jeweils 75 -125g Vitamin C haben gewirkt. Sogar beim unheimlichsten aller Krebse.
Quelle: PROC Nat Acad Sciences Vol 102 no. 38, 13604. Doi: 10.1073/pnas.0506390102