Reason for a New Age

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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