Reason for a New Age

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Gettin’ Old – Part 2

Posted by publius2point0 on 2016/07/03


The basic idea that I introduced in the previous article is the Cellular Theory of Aging. In that theory, we age because our cells age. If we can keep our cells healthy, then we can extend our lives.

That theory is clearly insufficient. It may be true – and the evidence on smaller, similar species would seem to back the idea that gains can be made to lifespan by taking better care of our cells – but not complete.

In all of the cases that I gave, in the previous article, the question was “How to keep things going longer, when everything is shutting down?” And that leads naturally to the question of, “Why is everything shutting down?”

So, counter to the Cellular Theory of Aging, there’s also the Programmed Theory of Aging. In this theory, it’s part of our basic design, to age and die.

This theory isn’t as well-supported as the Cellular, and there are some arguments against it. Specifically, the theory seems to give the idea that death is hard coded. That would mean that there should be a gene that we could turn on or off to cause death, or a set of genes that we could find that would indicate a specific age at which we will, by programming, die.

That idea, I think, is overstating the programming case. The critics are right that there isn’t a “die” button built into our DNA. But that doesn’t mean that there isn’t a button which puts us into a “stop maintenance and let the body slowly decay and break down” mode. That, I believe, does exist. And I think we can prove it fairly easily.

Simply put, the body has growth phases. We have growth spurts, we have puberty, some of us have menopause, and we have old age. As we transition from and to these different stages, our bodies develop in different ways, based on differing levels of hormones and genetic instructions. Levers are pulled and pushed, and they do so in a fairly consistent, timed manner. The Cellular Theory of Aging does not explain this sort of progression. The Cellular theory, as the name indicates, is concerned solely with our cells. The human body is bigger than that and, even if you think that the individuals cells could be supported indefinitely, they still are at the mercy of the whole system and the changes being made to it.

The Biologic Clock

There is, somewhere in the body, a clock. It dictates when the body transitions from one stage of life to the next, and when the clock rings, the body changes to match the next set of instructions. If you can stop the clock from progressing…maybe you could live forever?

Well, maybe. Maybe not. There might be more than one clock. And there may be no set of instructions which supports “stasis”.

Let me go into that in a bit more depth.

For the first one, how many clocks there are, let’s consider telomeres. The telomeres are a bit of extra data at the end of our DNA. When a cell splits, the DNA is cut lengthwise and each half receives a copy of the part that was lost, to create two new DNA strands that are copies of the original. The exact mechanics of this process involve some loss at the ends, so the telomeres provide some material that is safe to lose. Every time the DNA is copied, the length of the telomeres shortens with it, and eventually the cell could no longer be safely copied without loss. There is a cap on how many times we can create new cells. This is a hard limit on how long we can live – since eventually we will need to replace all of our cells. But it’s also a good clock, to tell how old we are. The shorter your telomeres, the older you are.

This feature could be a very clear-cut timer on which the body could make its decisions on when it is time to change gears. But, the evidence is mixed. Growing the length of telomeres (via the activation of telomerase) has both been shown to extend life and to do diddly-squat for extending life:

http://www.ncbi.nlm.nih.gov/pubmed/19145831

http://owndoc.com/anti-aging/ta65-revgenetics-cancer-fda-complaint/

And, from everything that I have read, I have not really found anything which seems to show a mechanism by which telomere length would actually affect the body. I haven’t seen any chemical reactions that seem to vary by length. (Though, obviously, I have not read everything that is out there and, even if I had, that doesn’t mean that we know everything there is to know about the human body.)

Within the body there are several things that change naturally over time, like this. It’s possible that it is the interaction of these different “clocks” that causes the body to change, rather than there being a single source that governs everything. The human body, after all, was not engineered to be simple and straight forward – it just evolved to be as it is through billions of years of trial and error.

And, to go a little bit off topic, if there is one thing that I have learned from all of this research it’s how complex the human body is. Generally we learn about our major organs. And yeah, we might have a few dozen of those. But within each cell, there’s hundreds of proteins, interacting with each other, DNA, and other cellular structures in thousands of processes. And these interactions are generally just small steps towards the eventual product. The human body is less like “a car” or some other simple machine, and more like the whole process of mining raw minerals to selling thousands of different products in hundreds of industries, in the global economy. At the cellular/protein/hormone level, the scope of things to track and follow is genuinely huge and it’s impressive that we have as much information as we do.

That aside done with, let’s get back to my other statement that there might not be such a thing as “stasis” in the human body. From everything we know of the human body, after all, we are either growing or we are declining. If we could stop “the clock” when we were 18, well we might end up growing and growing and growing, until we are 10 feet tall and our brains are causing our skulls to swell. At 18 we’re not growing very much. You’re basically the height that you always will be. But you are still growing just a little bit and, given eternity, that will eventually start to add up and cause problems. Halting the clock even earlier would be even worse – like if you’re in a growth spurt.

Our bodies cap out at around 25. After that, are our bodies maintaining themselves in a stable manner for a few years? I don’t know. Maybe and maybe not. Possibly, at 25, the off switch has been pushed and everything is in free fall after that point. Maybe there’s a transition sometime between 30 and 40 where we go from maintenance to free fall. I couldn’t say. But it’s likely that we’re basically in “off mode” after 25. Stopping the clock anywhere after that won’t do much, because there is nothing to be stopped. The levers have been pulled to their final position.

Menopause could be evidence against that view. Or it could be that menopause is just a side effect of the downwards spiral, and was triggered decades earlier. Again, there just isn’t enough information at the moment.

Overall, we don’t know what the biologic clock or clocks are, we don’t know how to stop them, and we don’t know that “stopping” them would actually produce a good result.

On the other hand, as I said earlier, the indication would be that once we go into decline it doesn’t mean that we are programmed to die. The evidence goes against that. It just means that the body isn’t going to naturally produce what it needs to maintain itself. That doesn’t mean that we can’t try to maintain it, despite our body’s wishes.

Some Possible Clocks

Besides the telomeres, I have identified three other “clocks”. Actually, only one is a clock and the other two would be better called “feedback mechanisms”. Together, these are telomeres, chromatin, inflammation/hypothalamus, and cortisol/adrenal gland.

Telomeres

I have already discussed this to some extent. As said before, it is a part of the body which the body could use as an internal clock. When cancer cells want to become immortal, they do almost always mutate so that they keep their telomeres growing. (Testing for heightened telomerase – the protein that reconstructs telomers – is one of the ways that doctors can test for cancer, and it is also one of the ways they target medications at cancerous cells.)

I have found two telomerase activators. One is TA-65, a purified extract (cycloastragenol) from the herb Astragalus. Based on the research that the company has published, it seems to be able to grow back telomeres at a faster rate than they shrink. On the other hand, based on their research, this does nothing to extend the lives of rats.

The man who discovered cycloastragenol recommends against trying the product unless you are pretty near the end of your life as there is a cancer risk, both in it possibly spurring on cancerous cells. Or, simply, by getting in the way of anti-cancer medications and tests. Of course, there’s some reason to believe that cells with short telomeres are more likely to become cancerous, so lengthening short telomeres (which telomerase does – it targets the shorter ones first) may help to protect against cancer…. It’s a big question mark.

If you do want to try it, it is quite expensive. The off-label brands that are supposedly 98% pure should be about half as effective (this page says that you need 50X the off-label stuff to match the effectiveness of TA-65, but whatever math they used is wrong. The area under the lines in the graphs shown indicate half-potency.)

Of course, you could just take regular astragalus supplements. These will not be anywhere near as potent, but it seems to be fairly good for the body and it lets you dabble in telomerase activation without the same fear of cancer. Plain astragalus is also quite cheap to supplement.

The other telomerase activator are tocotrienols, featured in the last article as a good anti-oxidant. Tocotrienols would seem to be a two-fer.

Chromatin

If there is a single, core biologic clock, my bet would be on chromatin.

DNA is a long string of data. Very long. A single strand, stretched out, would be taller than your average person. And yet, we have a copy in every cell in our body.

It’s thin and, more importantly, it’s in curlers. Chromatin is a structure of macromolecules that DNA winds itself around so that it can compact down in an ordered fashion, and also to help “armor” the DNA from damage.

But, importantly, it would seem that DNA is still used to produce new proteins and who knows what else on a constant basis. It’s used as instructions and as a building platform for some of the many chemicals floating around in our cells. And that can only be done if the chromatin unwinds to provide access to the correct locations.

As we age, though, we lose our chromatin. More locations for synthesis become open on the DNA, but the DNA is also more exposed to potentially harmful reactive oxygen species or other sources of damage.

But it seems like a rather simple way to set up an aging clock. If the body would build stuff, if it had access to the DNA, and the DNA slowly exposes itself, then the body will undergo changes through the simple process of DNA becoming disorganized and damaged. It would simply be a matter of making sure that the DNA becomes exposed in the right order at the right times, but that could come down entirely on evolution. Based on how the chromatin folds the DNA, certain spots will be more likely to decay first. DNA which has building points useful for growing properly in those places or useful for exposing the next correct places in the DNA, will produce creatures that are more likely to breed and propagate that set of DNA.

That may or may not be correct, but it does seem to be that it is through helping to protect our chromatin structure that the first and most studied form of life extension seems to function, that is to say, caloric restriction.

The evolution behind caloric restriction and life extension – a question I had pondered in the last article – would seem to be that the body is smart enough to understand that the natural life cycle of growth and death needs to take a break during times of food shortage. It seems to do exactly what we are suggesting here and puts a halt on the biologic clock, so that we maintain our health through the time of hunger, and then resumes once we are through it. We begin aging again.

When resources are plentiful, we want to make babies and die off, to give them room. If times are hard, we need to stay alive until things are good enough to make babies again. Our bodies help us do this.

And the way the body does this is by releasing sirtuins, which fall into the category of HDAC inhibitors. These modulate the histones (helper buddies) who move things in and out of the DNA for construction and hence which bits of DNA are exposed and for how long. Some of this may be helpful, and some harmful. There are different types of inhibitors and we are still trying to figure out how they affect things. Valproic acid, for example, is known to cause autism in the children of mothers who were taking it. They are not interchangeable, and they are not all necessarily good. In the case of sirtuins, they seem to do something that allows the chromatin to stay as it is longer.

The ones which may be good are the class III inhibitors. Amongst these, the ones which seem to be the most well-supported by science are resveratol, curcumin, and sulforaphane. Both curcumin and sulforaphane seem to have more evidence behind them, for effectiveness, than resveratol. Unfortunately, I have lost the cite which allowed me to make that determination, but you are encouraged to do further research. There are a number of potential/known inhibitors, and many of them have barely been studied:

https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/1868-7083-3-4

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210916/

Inflammation, NF-κB, and the Hypothalamus

NF-κB (nuclear factor kappa B) is a protein that cells use to inform the rest of the body of damage – e.g., from ROS’s or from other forms of damage. This signals to the body that it should send things in to help fix the problem.

Theoretically, this should be a good thing.

But, as we age, the amount of NF-κB is constantly raised, and the hypothalamus seems to use the level of inflammation in the body as a clock to module GnRH, a hormone that tells the body how much of other hormones to make. As time goes on, the balance of our hormones gets thrown off, causing the body to perform worse, raising the level of damage to our cells, raising the level of NF-κB. It is a positive feedback loop that seems to shorten our lives, compared to if we inhibit NF-κB as we start to age.

(Technically, NF-κB causes IKKβ production, which causes GnRH production, which causes the hormone modulation, and all of the inhibitors are for IKKβ. But NF-κB is the start of the chain.)

There are a number of known IKKβ inhibitors, but the best source that I found of inhibitors used a programmatic model to identify possible inhibitors for future study. But the top rated ones by the progam model do seem to be positively correlated to life extension. And, I would note, they also all seem to be linked to cancer prevention.

I discovered this while researching ways to protect against cancer, due to the concerns with telomerase activators. It seemed like one might safely try astragalus, so long as he was also taking something which helped to protect against cancer.

The best protection against cancer is p53, a protein that is able to find and repair mutated DNA. Besides the worry with telomerase, anti-oxidants also tend to lower p53 activation, as they prevent DNA damage from occurring. But, it seems like it is better to have p53 around checking our DNA at a higher rate than is spurred by ROS hits, as p53 activators do seem to reduce cancer rates. Genistein – a known p53 activator – is a soy product. The Japanese, who eat a lot of soy, have 2/3rds the rate of cancer as Western societies (like the USA), despite probably having a higher rate of smoking. Not necessarily great evidence, as Argentina also has lower cancer rates. But in my research, I noticed that there was a significant overlap between IKKβ inhibitors and p53 activators. The top rated IKKβ inhibitor that the the program identified, boswellic acid, seems to do amazingly well to fight cancer. Others that I have found and checked are hesperidin and ursolic acid. They all score well against cancer, for inhibiting (or believed to inhibit) IKKβ, and are positively correlated with increased lifespan.

How much the lifespan change is due to a reduction to cancer versus achieving stasis in hormones, I couldn’t say. But the indication seems positive in either case.

Cortisol, Stress, and the Adrenal Gland

This one, I have not researched greatly. But it seems to form a similar feedback loop as NF-κB and the hypothalamus.

When we are stressed, the adrenal gland produces cortisol. Cortisol is the “stress” hormone and it puts our bodies into a fight-or-flight mode, which readies the body for physical action, turning everything up to 11, even though the system is only rated to run in the 5-6 range. Being outside of the right range adds wear and tear on the body (yes, that’s a bit vague, but that seems to be the high level description), and you live for less long.

Theoretically, stress should be a short, situation specific state, like facing off against a lion. But it’s believed that in modern day, with tight deadlines and a busy schedule, we end up with a constantly raised level of cortisol in comparison with our human ancestors.

But even outside of that, it seems to be that our cortisol rate generally rises with age and that would, probably form a feedback loop. It causes our bodies to wear out faster, which will stress us out, which will raise our cortisol level even more.

Strangely, there doesn’t seem to be a large number of cortisol blockers. But the one which seems to work is rhodiola rosea. And yes, taking it regularly does seem to extend lifespan.

A Second Menu

In the previous article, I suggested resveratol. In light of new information, I would suggest swapping this with curcumin or sulforaphane.

Atragalus root extract, and tocotrienols can be used to grow your telomeres. Tocotrienols are good anti-oxidants. Be careful using TA-65 or cycloastragenol.

Boswellic acid seems to be the best IKKβ inhibitor / p53 promoter, but hesperidin and genistein are good alternatives.

Rhodiola rosea seems to be the only cortisol blocker.

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Gettin’ Old

Posted by publius2point0 on 2016/05/07


NOTE: I am not a doctor nor aging scientist. I’m just a guy with access to the Wikipedia and Google. Don’t take any of this as health advice, let alone good health advice.

I don’t recall where, but recently I was reading about Leonard Guarente and the business he was starting, with a number of Nobel Prize winners on the board of directors, to develop supplements and (perhaps) medications that will slow down aging. Since my Food & Diet articles (of which, a third entry is still planned), which required reading through a lot of Wikipedia articles with fun snippets of information like:

The GHRL gene produces mRNA which has four exons. Five products arise: the first is the 117-amino acid preproghrelin. (It is homologous to promotilin; both are members of the motilin family). It is cleaved to produce proghrelin which is cleaved to produce a 28-amino acid ghrelin (unacylated) and C-ghrelin(acylated). Obestatin is presumed to be cleaved from C-ghrelin.

I’ve ended up researching a few other body chemistry topics and gotten a little bit better at not getting lost in the overly-technical parts, so it seemed worth doing a review of the current state of anti-aging technology. After all, I’d like to live longer than shorter, if I have the option.

At the moment, longevity research appears to be focused on the life of cells in our bodies. This is as opposed to say, creating mechanical hearts and lungs that last forever, or using gene therapy to turn off aging, etc. And I think that’s fine. The whole body is, after all, made of cells and keeping them fit and vigorous may well do the same for the body as a whole. It isn’t an unreasonable direction of research.

Reactive Oxygen Species

Let’s review what a cell is really quickly:

 

 

 

We have a fleshy wall (the membrane) which is filled with goo (cytoplasm) with various things floating in it. An egg is a large, single cell where there’s a hard shell attached the outside of the membrane. The white is the cytoplasm and the yolk is the nucleus. I’m not sure (but suspect) that not every cell has everything listed in the above image, since I’ve never noticed a centrosome in my hard boiled egg, but the key point is that there can be a number of extra elements floating around in a cell than just the nucleus (yolk).

For our purposes, the important guy is the mitochondria.

The mitochondria is largely concerned with processing food into energy (ATP) for the cell. It has other tasks, like signalling the cell to begin apoptosis (cell death) once it decides that it’s time to go, but for our discussion these other capabilities aren’t relevant (even the apoptosis one).

Part of the process of converting everything the cell receives into ATP involves the creation of free radicals, which are molecules that are electrically unbalanced. These sorts of molecules tend to be highly reactive and, thus, react with the things around them. Chemical reactions, at any zoom level, tend to be hot, explodey messes and the result of having a lot of them around is that it tends to damage the mitochondria, destroying their productivity, and bringing on cell death more quickly.

To counter this, cells produce a number of anti-oxidants (oxygen atoms are generally the reactive atom in free radicals, hence the reference), like catalase and glutathione. These react with the reactive oxygen species (ROSs or “free radicals in doctor speak, instead of chemist speak”) before they can react with the mitochondria. You can think of it like shooting down missiles while they’re in mid-air.

And, as noted before, the general theory is that there’s a relationship between how healthy and long-lived our cells are and how healthy and long-lived we are.

And in tests, there does seem to be some truth to this. By toying with the levels of anti-oxidants in an organism’s body, for example, scientists have shown that they can extend the life of some classes of animals. It’s theorized, for example, that the longevity of the French may be due to resveratrol – an anti-oxidant found in red wine, which the French drink a lot of. Tests on resveratrol haven’t been a rip-roaring success, though, with some studies confirming and others not, the life extending capabilities of the molecule. Tocotrienols (a sub-type of Vitamin E), for example, seem to improve the mean life span of C. Elegans.

Of course, the mean life span and the maximum life span are different things. Take note of that. I’ll come back to it later.

This isn’t to say that more anti-oxidants are better. There’s a certain quantity at which a cell is the most well fine-tuned it is going to get. Beyond that, and you’re swamping out other useful chemicals that are needed with excess anti-oxidants (and some anti-oxidants can cause liver damage if ingested in doses too large). But, importantly, catalase, glutathione, and perhaps other anti-oxidants all seem to be produced in lower amounts in all (or most) of the body’s cells as we age. In our old age, our cells are – from day one – less well protected against reactive oxygen species, and they die quicker. And so, the theory goes, raising the anti-oxidant levels back up to the levels that we would want, when we’re old, might help to extend our lives.

There are two other theories, roaming around, about how to keep your cells healthy.

The Electron Transport Chain

The mitochondria, as we have said, creates ATP (energy) for the cell to use. At the level of your average cell, this really comes down to chemistry: Hard, atomic chemistry. For everything to get processed correctly, the right mixture of compounds, with the right number of electrons need to exist, and the ability to move those electrons down the chain is a big part of efficiently creating ATP, and thus keeping the rest of the cell well-fed and able to do the things it does.

And similar to how our anti-oxidant levels deplete as we age, scientists have noted that a few key ingredients of the chemistry chain – you might view them as engine lubricant – also are produced in lower doses when we are old, than when we are young: NAD+ and CoQ10.

In this case, where scientists have tried to boost the levels of these chemicals, they have seen extensions to the max lifespan of the animals hosting those cells.

There has also been research into resveratrol on this line as well. One early discovery, in aging science, was that animals who are given lower levels of food (while still getting enough calories and nutrients to survive) live longer than animals that are able to eat (or overeat) more freely. The research seemed to lead to a class of chemicals, sirtuins, which were produced by the body in lower-calorie conditions, that seemed to improve the ability of mitochondria to make energy. Basically, when there’s less food, our body configures itself to run more optimally and lasts longer. (Whatever evolutionary pathway produced that result, I don’t know, but it’s rather interesting). Unfortunately, sirtuins are proteins. If you eat a handful of sirtuins, they’ll just be dissolved by the stomach and become food, not bonus sirtuins. (This is also true for the anti-oxidant, catalase.)

But, somewhere in your body, sirtuins are made. It was thought that it may be possible to signal your body to make more by hitting the SIRT1  receptor (e.g., the ‘on’ button), and it was thought that resveratrol may be a SIRT1 signalling chemical.

Again, the results of that specific study seem to be a bit iffy.

Human Growth Hormone

While more complex than this, it could be said that growth hormone…well, makes you grow. Specifically, it makes you make new cells.

As we age, the amount of growth hormone in our bodies diminishes. It might make sense then that, if we want to be like our younger selves, we need to be able to replace our dying cells with new ones, and we won’t be able to do that if we lack growth hormone.

BUT, unlike previous tests, when the hormone was boosted in animals, their lives were shortened. The theory would seem to be that, as we age, we end up accumulating cancerous cells. When you apply growth hormone to cancerous cells, you get a lot more cancerous cells. So, whereas it’s bad when other chemicals are reduced as we age, this one seems to be better reduced. In fact, those with less growth hormone tend to live longer.

Ruminations

I’ll liken everything to the following:

You own a farm, growing plants. To effectively grow plants at peak, you need to:

  1. Protect from weeds and invasive species.
  2. Provide fertilizer.
  3. Provide water.

Over time, if these three all decrease – you stop weeding, you don’t stock up on fertilizer, and your watering pipeline breaks – your farm is going to get overrun, whither, and go defunct.

If, over time, 1 and 2 decrease – you stop weeding and you stop buying fertilizer, but you do continue to water your farm – your farm will last longer than if you hadn’t. There will be a lot of weeds, but your own plants will still be in there fighting alongside them, since there’s at least some (though incomplete) nutrition still coming in. No new plants will be able to grow, though.

If, over time, 2 and 3 decrease – you stop buying fertilizer and your watering pipeline breaks, but you keep weeding – Your plants won’t be competing for the limited resources with the weeds, so they’ll do pretty good at first. But they’re still on a pretty definite timetable. Once the land dries out, they’re going to be gone.

These seem to be, relatively, the effects of improving the electron transport chain in an aging body or, instead, increasing anti-oxidants. In the former case, you get a little bit more life (max life) out of your plants. They’re not necessarily healthy, but they keep ticking. In the latter, we’re clearing out the weeds, so everything seems healthy and happy, right up to the point where reality kicks in. We achieve a healthier life, but it’s not really extended.

And if we then think about just #2. We feed the plants. There’s a bunch of weeds out there and, being more hardy than what we grow, with even a little bit of fertilizer are going to perform a lot better than the non-weeds. My plants will do pretty well, at first, as well. But in the long run, they’re getting a 1-2 punch. Weeds are choking them out, and the land is drying out. Adding the fertilizer, in the end, just kills my farm quicker.

Now if this illustration was correct, it’s safe to add fertilizer (growth hormone) so long as we keep weeding (anti-oxidants) and keep watering (electron chain). And, really, the only way to keep the farm running endlessly, rather than just extending it to a later death, is to do all three in the proper ratio. It just seems that it is dangerous to fertilize, when you test that one variable, without including the others.

And we know, since we can look at our bodies’ chemistry before 25, that higher levels of growth hormone don’t necessarily lead to cancer. Most 19 year olds, for example, do not have cancer, despite a significantly higher level of growth hormone than your average 70 year old.

This is assuming that the analogy isn’t a false analogy, though.

Cancer

Everything causes cancer. You’re out of luck on that one.

For our discussion, the important thing to note is that all of the previous discussion of the cell, our main target was the mitochondria. But here, I believe, we need to move to the nucleus.

I would like to liken the nucleus of a cell to the brain (where the mitochondria could be compared to the gut), but really the human body doesn’t seem to have quite the same organ – or not one that I know the name of off the top of my head. It stores DNA and other bits of data that provide the cell the ability to produce the other parts of itself (like ribosomes) or to create new cells with the same DNA.

And, it is changes to that DNA – mutations of the cell’s genes – which can create cancerous cells. And, as noted, everything causes cancer. DNA mutates. That’s, really, part of its purpose. When two people mate, their DNA are mixed, a little bit of random mutation (I think I recall that about 2% of the DNA is random) is inserted, and you end up with something for evolution to test out for fitness. The problem is when a cell’s child gains a mutation that allows it to out-compete all of its neighbors, and it begins to grow and spread, out of control.

Our bodies, in fact, always have a few cells that are trying to become cancerous. It’s just a side effect of life. But, when we are young, generally our bodies recognize and shut down these cells before the genetic progression of they and their progeny can continue on to genuine cancer.

So…do free radical explosions make it more likely for a cell’s DNA to mutate? If not, then pumping anti-oxidants wouldn’t help to protect against the risk of increasing your growth hormone levels. But it does seem to be that ROSs do cause increased rates of cancer. And that makes some sense. While, I assume, most ROS explosions occur near the mitochondria – since that’s where the free radicals are being produced as a waste product – the more ROSs floating around in general and the more explosions that occur in the cell, the higher the probability of the nucleus being affected.

But, that doesn’t mean that free radicals are the only or principal cause of cancerous cells. Saying that anti-oxidants can reduce incidences of cancer doesn’t mean that they reduce most incidences of cancer.

After all, the human body doesn’t fight dangerous-looking cells with anti-oxidants when we’re young. Instead it sends things like P-53, a protein that can repair DNA or command a cell to die without making children. If P-53 does 90% of the work of protecting us from cancer when we’re young, but we stop producing it later in life, then start pumping up growth hormone, it might not matter much that we’re taking anti-oxidants. It’s better than nothing, but still can only be 10% of what we need.

So…does P-53 decrease with age? So far, I do not see any information saying that it does. Which would seem to imply that the main protection is and will always be there (as seems BRCA1, another tumor suppressor), so it may just be the decreased level of anti-oxidants that accounts for the diminished protection against cancers in the elderly.

But, two more hypotheses that I could offer are:

  1. Regardless of all protective measures, some things will slip through the cracks. Eventually, mutations will build up in the human body, and eventually some of those mutations will become cancerous. The longer you live, the higher the probability of cancer, period.
  2. As the body ages, and the health of cells declines, it is easier for strange cells to co-opt resources and begin taking over. Besides anti-oxidants and tumor suppressors, the competition with normal, evolutionarily successful cells provides a strong defense against weird, malformed cells.

In the case of the first, you would want to keep away from growth hormone. In the case of the second, if you can keep your cells healthy, you’re taking anti-oxidants, your body is producing p-53 as always, then growth hormone becomes safe.

Unfortunately, I’m pretty sure that the first one is true. But I would bet on the second also being true as well. So the end result, per individual, is probably just up to the luck of the draw.

Supplementation

There are, in general, four ways of supplementing a missing or reduced chemical in your body:

  1. Inject the chemical.
  2. Ingest the chemical.
  3. Ingest the precursors of the chemical.
  4. Ingest a signal for the chemical.

The first is the most straightforward. For example, if you want to boost your HGH, you could inject HGH right into your body. But, practically speaking, it’s not feasible for most of us to receive regular injections of strange substances that aren’t mass-produced for general consumption. And then, who knows where it came from and what it was cut with? (HGH possession is illegal as well.)

Most of us choose to go for option 2. And for most supplements that works, since most supplements are vitamins. Our digestive system was built to take vitamins in, so that makes sense. (Whether they’re still those same chemicals in your blood stream, I couldn’t say though.)

As noted before, though, some things can’t make it through your digestive system. Or, later, they might not be able to make it through the blood-brain barrier or otherwise get to where they are needed from the digestive system. For example, there was a company selling catalase as “Go Away Grey“, saying that it would help to reduce hydrogen peroxide in your body, which was killing hair cells and causing grey hairs. The FTC was rather displeased with this since catalase is a protein and will not become catalase in the body, being mulched by the digestive system instead.

So that leaves us with options 3 and 4. In both cases, the idea is that your body can and wants to produce the chemical, it just needs some help doing it. In the first case, we’re assuming that the appropriate input chemicals for production are missing, so the body isn’t producing them like it should. But if those chemicals can be digested, then eating them will result in the target chemical being raised.

Similarly, with #4, the body is able to produce the chemical, but requires some sort of stimulus to do so. Sirtuins, for example, are released when the body detects that we’re just barely getting by. If you can ingest something that makes the body think that, then you’ll get more sirtuins.

Of course, all of this depends on the company in question actually providing what they say they will. Supplement vendors aren’t well-policed to provide the exact compounds that they say they are providing, in the exact dosage indicated on the box. As of yet, I’ve found no good way to ascertain which companies are honest. I can only recommend brand recognition. A bigger company has more to lose by being caught out, and more opportunity to have that happen. (But they may have gotten big by cutting more corners so….)

In all cases, beware dosages. Unfortunately, there’s no standardised test for cell health. Testing cell proteins/hormones/etc. require scientists taking brain, liver, and other biopsies to determine the current status. Too high on some supplements and you’ll be looking at liver damage, poisoned cells, etc.

A Menu

A simple cell functions on the basis of dozens, hundreds, or some otherwise middle-large number of independent chemical reactions. Catalase is a major anti-oxidant, for example, but there are a number of them, each service different purposes. Similarly, there are a lot of components in the electron transport chain or cell growth. While I wouldn’t historically be considered a ‘pill popper’, I would say that if you want to try supplementing your aging cellular system, a ‘cocktail’ may be the right answer.

Personally, I have decided to make a go of it (as I can afford it), and have purchased:

  1. Powdered colostrum  – precursor for growth hormone, IGF-1, and (probably, since whey protein is) a precursor for glutathione (a core anti-oxidant)
  2. CoQ10 – Part of the electron transport chain
  3. Resveratrol – Possible low-level anti-oxidant. Possible low-level sirtuin activator
  4. Tocotrienols (Red Palm Oil) – Alternative hydrogen peroxide antioxidant to catalase
  5. Nicotinamide Ribosone – Precursor to NAD+

As you might note, I have gone the pro-growth hormone route. My logic is that 1) I drink a ton of milk, which is apparently the only way to really stimulate growth hormone in a human, short of injecting it, so I’m already up a creek, 2) despite the science, if you plot out cancer rates by country and milk consumption for those same countries, there’s either no or negative correlation, so I’m a bit skeptical of the hormone producing capabilities of milk (and, thus, colostrum) or the cancer-causing effect that it is supposed to have. The non-quack studies that I read do indicate a genuine increase in hormone levels though, so…buyer be warned.

And despite all of the tepid recommendations for resveratrol, it seems more likely that it’s simply a relatively small-time contributor in both of the categories it competes in. It provides a backup in two fields.

I will make no note of the dosages I have chosen as I am not satisfied with the data I have been able to find and do not want to recommend something dangerous to others.

I’ll let you know how it works in 80 years!

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Pinochet, Putin, and the Bushes

Posted by publius2point0 on 2012/09/09


On a set of forums that I frequent, one of the posters who had spent several years living abroad in Africa and China made the following comment on her experience of Africa:

It is true that in the past Africa was not that different than the rest of the world- The average person scratched out a living on a farm, birthed and buried a pile of kids, and paid tributes to the local warlord/chief/lord/whatever. A smaller portion of people lived in crowded disease-ridden cities where they engaged in trade and light manufacturing. The elites had lots of shiny stuff and occasionally put on a war. After a certain point the big evangelical religions began to overpower and get mixed up with local beliefs. People were really into believing in witches. 

You seem to forget that even individual European countries have not been unified that long. Not long ago places like Germany and Italy were just loose alliances of local warlords. We call the “Ibo” a tribe, and we call the “Catalonians” something else, but it boils down to the same thing. Feudalism ruled- and Africa had pretty much the exact same feudal system. Huge areas- like much of what is now Russia- remained sparsely populated and poorly explored because the climate sucked…kind of like a lot of Africa. Perhaps these moments of development were not perfectly lined up across the continents, but if you brought a Russian serf from 1400 and had him trade place with an African serf from 1400, I don’t think it’d be that big of a downgrade in standard of living.

I do not believe that without colonialism Africa would have developed exactly the same as Europe and have never said that. Africa has some massive climate challenges that would make that nearly impossible. Europe developed technology that probably would not have developed in Africa for a number of reasons. 

I don’t think it’s accurate to say that Africa degraded into a uniquely wretched state. For the average person, things didn’t really go downhill as much as they just didn’t move forward. For most of history famine, ignorance and disease was the norm. Life, historically, is tough. It just never stopped being tough in much of Africa. Many places are in a bit of a middle-ages time warp. 

I gravitate towards the middle ages because that is what it felt like to me. Living in Cameroon felt oddly familiar, and it took me a bit to realize that it was because it felt like a fairly tale. I was friends with the baker, the tailor and the brewer. I knew bored princes that would pose as commoners for a bit of fun, and princess who hated being locked up in seclusion. People worried about witches and poisoned wells. The rich guy down the street got all his money from an enchanted parrot who guarded a magic ring. It was right out of the pages of Grimm’s. 

Anyway, where colonialism and the Cold War come in is that they took the already difficult situation of this level of development and gave it bigger guns and higher stakes. What would normally be a family feud could become a genocide. The greedy kings suddenly got oil and diamonds to plunder.

The original President Bush was, for about a year, the director of the CIA with the task being to reorganize and restructure the agency. While there is a general dearth of information on his actions other than this, one can presume that reviewing the effects of the CIA’s attempts at nation-making in the Americas, and elsewhere, through the 60s and 70s as a response to the Red Threat.

I make that assumption due to the unexpected and unforeseen conclusion of the Gulf War, where President Bush decided to leave a genocidal narcissist who hated the United States in his position as the ruler of a nation of about 18 million people. Why do that?

The hard truth, learned by our nation during the 70s and 80s, is that in a nation ruled by tyrants, kicking out the tyrant and instituting a modern government merely results in a new tyrant who has to point guns every few years to get himself re-elected. Between each tyrant is a period of chaos and death. When a new one comes into power, his first job is to slaughter all of his political enemies and everyone related to them. If it was a clash between different races or sects, then genocide becomes part of it.

To explain this, let’s take for example a dog. If you get a young puppy and are cruel to it, training it to attack and kill all other dogs and people who come near it until it is an adult, then you’ve created what is and will almost certainly always be a risky creature. The only solution is to put it down. While we like to think that humans are different from this, because we can learn new things and reason, in reality only a small percentage of people are disciplined enough to make such a change, if any at all.

If I’m a peasant farmer and the local warlord dies, leaving a power vacuum, and some white guy from another continent tells me that I can become the new warlord if I convince enough people to vote for me, my thought isn’t, “I’d love to serve my fellow farmers and make their world a better place.” It’s, “Wow, I can have ten wives and not be hungry any more!” He has no understanding of a world outside that which he knows. He doesn’t view the position of warlord – under whatever title the Americans might call it – anything other than the position which he has always known it. He doesn’t have the benefit of an outside viewpoint or any knowledge of how to get it there.

More importantly, even if you look at dictators who did have a foreign education in the US, the UK, France, or elsewhere, you’ll notice that they don’t behave much differently from anyone else who is able to take over the old dictator’s job. Simply put, he’d die if he was any less harsh or ruthless than his predecessor.

Everything about wielding power comes down to respect. If you can’t get the respect of any of the people who are under you, then you’re not going to accomplish a thing. If their vision of what it takes to be respectable is to be a fierce, scary murderer, then going about talking about saving the rain forest and being “the servant of the people” is just going to leave you as a worthless lame duck who’s filling a position of power and luxury that someone else would be quite happy to take from you.

There is a reason that Putin is, for all intents and purposes, a mafia boss running a nation and that’s because for the last 80 years, it has taken that sort of person to run the nation. If he didn’t, he would be ousted, either by his people for being useless, or by someone else who is willing to be the psychopath that it takes to get the job done.

Now, none of this means that a nation can’t be transformed into a modern nation with a republican form of government and a free market. But in order for it to  happen in anything less than some form of natural evolution, at least one or two generations will have to pass, with a concerted effort on the part of the leadership to remove corruption, hire only idealist pansies in any government or professional positions, all while teaching modern philosophies of human rights and the free market to toddlers. No outsider could ever impose such a level of reform except through complete ownership and direct control of every level of government, the economy, and the educational system.

Subsequently, the only two places to succeed (that I can think of) are Chile, under Pinochet, and Japan during the Meiji reconstruction.

And you’ll note that Pinochet was by all accounts an evil, domineering tyrant. He tortured and killed all political enemies, real or imagined. Had he not been, though, it is likely that he never would have been able to accomplish what he did and created a nation capable of joining the modern world.

The point of the opening quote about Africa – besides being generally educational – is that the big gulf between the US and Africa, South America, or the Middle East isn’t to do with the structure of government or economic freedoms, it’s to do with world views. Sticking a gun in Lancelot’s hand doesn’t make him a modern man, it makes him a feudal knight with a gun. He’s going to go out riding, shooting people to death who don’t tell him where to find the Holy Grail because that’s what his Lord told him to do. He’s not going to rise up and start fighting for peasants. Why in the world would he ever do that?

And subsequently, this is where the younger Bush showed himself to be one of the larger idiots in the history of man. I could forgive any other American for not realizing what it means to stick your nose into the political realities of a backwards nation, but the son of a man whose career dealt almost exclusively with that issue to not have learned a thing about it is astounding.

If the younger Bush had rode in, individually hunted down and assassinated each member of the Taliban plus Saddam Hussein, fine. But if you decide to occupy a nation, with the intent of restructuring its government and way of life, then you are effectively stating your desire to be or elect a tyrannical dictator with full force to commit murder at will, suppress freedom of speech, and go on without popular support for the next 20 to 40 years. If you can’t, politically, financially, or morally commit to such an action, then you will be a failure.

In closing, though I am mildly doubtful that Putin reads my blog, I’ll just make a note that while he can feel satisfied about having his picture posted on every wall in Russia today, if he wants to be remembered in History, then he is going to need to start down the same path as Pinochet and rebuilding the world view of his government and people. Otherwise, he is just one more dictator in the bucket.

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