Exercise and cancer- why it helps and how much is enough? (part 1)

Posted on May 2, 2016

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This is a four part series-

Why exercise helps

The way cancer is referenced in pop culture it’s easy to think it’s like Ebola. That it’s some other species we happened to encounter one day, which has found it’s way into our body, that we need to “fight.”

So and so was recently diagnosed with X type of cancer:

  • “I intend to fight this disease.”
  • “I will beat this.”
  • “I will not let the cancer win.”
  • “Fuck cancer.”

We’ve even been at war with cancer!

War drives up connotations of destroying the enemy, using brute force, violence. It’s important to understand cancer is largely something gone wrong from within you. It’s not some foreign species entered our cells causing our cells to go wrong; it’s our cells went wrong. While it could be random or due to something completely out of your control, the cancer could very well be caused by something you did. You beating the crap out of a particular part of your body may be why you got the cancer to begin with. Excessive smoking or drinking being the most common examples. Those tissues may be at war with your own behavior. You saying “Eff cancer” could be like saying “Eff myself for the things I did.”

A less common example increasing the odds of getting cancer is a lack of physical activity.

But why?

A little appreciation for why exercise helps mitigate cancer risk can be helpful. Sure, we all know exercise is something we should be doing, just like we all know we shouldn’t smoke, but a little understanding behind it may be more influential. It doesn’t seem the connection between exercise and cancer is as well known either.

“Don’t smoke.”

“Why?”

“Cause it’s bad”

[goes off and smokes]

Compared to-

“Don’t smoke.

“Why?”

“Cause this:

[son of a bitch I’m never smoking]

This won’t be a heavy lecture on molecular genetics. A few points and a few minutes is all. (If someone with a stronger background on the molecular side feels something could be more accurate, please let me know.)

Many are familiar with DNA.

It’s made up of these forever and ever string of letters. Our genetic code.

dna sequence genetic code

As this is what makes us who we are, much has been written about this code. Much has been fantasized about it. Craig Venter’s group first sequenced the full human genome in 2000. Yet in 2010 he mentioned a whole lot of not much has happened since then. The fantasy is ongoing.

Perhaps you’ve known identical twins. I actually train a pair, who are almost 60 years old. Once around twins for a while, inevitably you notice many differences, to where distinguishing them becomes easier and easier. If you’ve been around twins older in age, this will be even easier as the differences will be more pronounced. Because I exercise these twins, I can tell you there are many more differences than appearance. One has a knack for running, while the other a knack for lifting. Well actually, one is quite good at upper body lifting, but the other at lower body lifting. Furthermore, one is much more relaxed about their training, happy to have a light day, while the other would go 100% everyday if they could.

These are people with identical DNA, right? What’s up?

Identical DNA isn’t really accurate. Identical DNA sequences is. But what’s on that DNA, how it’s coiled, is all but identical.

DNA is not by itself. It’s wrapped around these objects called histones. These little balls.

dna to nucleosome to chromatin

DNA is negatively charged, while histones are positively. They’re attracted to one another.

These balls come in packages of other balls, and have tails:

closer up histone and dna with tails

DNA is in black. There are eight balls, four on each side in this picture, in each ball. (Credit: http://www.nature.com/nrc/journal/v1/n3/fig_tab/nrc1201-194a_F1.html )

Precursor to main point

These tails of the balls, and DNA which wraps them, can all acquire or unacquire other molecules. Methyl groups, acetyl groups, phosphoryl groups. These groups modify the histone and or DNA. (There are at least 100 ways to modify just the histone.) They don’t change the sequence of letters, but they can change how the letters are read.

These other groups are also negatively or positively charged. By attaching to the tails or DNA, they can change how tightly wrapped the two are. For instance, keep the DNA at its same negative charge, but make the ball more negative when it was positive, and the two won’t be as close together.

Based on how tightly things are put together, other objects can more or less easily get in to read the letters.

43 second video:

These groups can also block certain areas from being read just by being in the way. (Longer video.)

We have a book which can be dictated as to which pages are stuck together and which aren’t, as well as if a page is open, how open is it? It might be open, but is something in front of it blocking the view of certain sentences? We can’t seem to preferentially change the letters of the book, but we can change how it’s read. (We’re ignoring genetic engineering right now.)

Think back to cancer. Most of the cancer everyday people encounter is not someone is born with a tumor. It’s not that someone is born with a malignant sequence. It’s later in life something pops up on a routine physical, you feel a lump out of nowhere. This is the more familiar case.

The letters of your DNA may not have been changed. The change may be in how the DNA is being read. In cancer caused by HPV, it’s not as if once you get the virus you get the cancer. Something goes awry. Identical twins don’t get identical cancers at identical times in their lives. This is at least one reason why.

For example, one day, or over the course of many years, maybe some genes -pages of the book we read- which help make sure cells don’t grow out of control,  maybe these pages of the book get closed for some reason. Next thing you know, we don’t as easily control certain cells, they grow out of control, and cancer results.

We also have machinery telling cells to grow. One day, maybe their pages start getting read over and over, too easily. Like someone using the same joke too many times. Things affiliated with that gene grow more than they should, and cancer results.

Even in those with the BRCA mutation, which has been highly correlated with breast cancer risk, it’s not as if the person is born with breast cancer. It still often takes a few decades, at least, for it to happen, if ever. The mutation is not a guarantee of cancer, it’s instead a huge increase in probability of cell growth gone awry.

Main point

These groups we’ve gone over which change expression, these genes which regulate how much things grow or don’t, ideally we’d be able to go one by one and go, and know where to say “turn on this amount, eh, you turn off, ok maybe you be on for half the time.” That’s the panacea. While people are hard at work on that, DNA has six billion lettersIf not wrapped around histones (the balls), it can stretch to be six feet in length. That’s from one cell. Add it all up and we’re talking a trip to the sun and back. 70 times.

There is so much wrapping and so many balls, this six feet can be condensed down to 90 micrometers. Six feet can be brought down to 0.0003 feet.

This is no ordinary book!

Each ball is really eight balls though. And each ball has a tail. Eight tails total.

By the way, we have ~70 trillion cells in the body. So 70 trillion multiplied by something like 6 feet of DNA can add or subtract these methyl, acetyl, phosporyl groups. An ungodly amount of balls can do the same thing.

1) Other modifications can happen not mentioned.

-> We have these things called microRNAs. Rather than manipulate how open or closed the DNA and balls are, they appear to work by getting messages out of DNA, but then not translating them. They’ll read the page to themselves, but not to someone else. There are at least hundreds of microRNAs. We know for 87 of them, each one has 400 targets. Each target has 4-5 sites….Let’s put this another way, in the last decade there have been more than twenty five thousand papers published on microRNAs alone! (More details on microRNA.)

-> 85 proteins can be involved in the process of manipulating the expression of one gene. These 85 proteins have more than one combination in which they can work. (Meaning a lot of combinations.) Depending on where the cell is during development, more combinations can occur. So all the combinations multiplied by all the different stages of development. When manipulating one gene, you can end up also manipulating a gene one million base pairs away. (This is a hot topic in molecular biology, but I like to think of it as you can’t pull on one part of a rope (DNA) without influencing every other part.) (More here.) For instance, we recently discovered a gene thought to suppress certain cancers, may assist the development of another! 

2) We’re in the process of discovering more ways which things can be modified. In the midst of writing this, there was a new finding. We’re just getting started in this world.

3) Many of the diseases we worry about nowadays happen later in life. It seems we’re not born with a negative sequence defect so much as the expression of the sequence gets messed up at some point. The expression element has all the variables of the sequence, plus A LOT more.

In other words, good luck with the engineering approach. It’s commendable, just good luck.

-> In some sense, trying to combat certain diseases with genetic engineering is like trying to genetically combat diabetes. Some may have an elevated risk, but you can address that genetic component all you want; if you don’t address someone’s behavior through their lifespan, it’s probably all for nought.

However, we know we have some power over expression. We know what excessive smoking and drinking can do to us. What if we could step back and say alright, look, going gene by gene, turning up and down what we want isn’t practical, at least right now. But are there behaviors which happen to correlate to genes turning down and up, and can these behaviors manipulate the genes we want? Where we can hit a ton of them at once? Besides not doing certain behaviors, are there things we can do to help?

Why yes there is! Exercise!

Stopping the why

We’re not going to go into why exercise does what it does anymore than the above. For whatever reason, we will see it has beneficial influences on cancer, and epigenetics -expression of genes- is partly, if not significantly, responsible. If you want a more in depth look at this, such as specific genes and more, see here.

When we consider how many things happen when we exercise: increase in heat, increase in circulation, increase in perfusion, intervals of compression and decompression, psychological highs, increase in lactic acid, hormonal changes, inflammatory responses. It is an endless list. Why these things help, which ones help more than others, it’s never ending, and one has to wonder how deductive you can, or want to, get. (Maybe it’s the confluence, not only one factor!)

The rationale for the above is we don’t need to wait for gene therapy, or genetic engineering, to influence our genetics. Exercise can manipulate how our book is read. It can add groups, subtract groups, open pages, close pages. Exercise IS (epi)gene therapy!

Part two- 

On why- a more serious look by Richard Feynman; a humorous one by Louis C.K:

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