Exercise and Caffeine May Activate Metabolic Genes 148
ananyo writes "A trip to the gym could mean not just losing pounds — but also chemical modifications from DNA in the form of methyl groups. The presence (or absence) of methyl groups at certain positions on DNA can affect gene expression. Researchers at the Karolinska Institute in Stockholm looked at the methylation status of genes in small biopsies taken from the thigh muscles of healthy young adults before and after a stint on an exercise bike. They found that, for some genes involved in energy metabolism, the workout demethylated the promoter regions (stretches of DNA that facilitate the transcription of particular genes). Genes unrelated to metabolism remained methylated. Furthermore, similar demethylation could be seen when cultured muscle cells were given a massive (probably lethal) dose of caffeine."
Re:OK, but.... (Score:4, Interesting)
Or if that's still unreadable, exercise changes how much some genes are active in muscle cells.
So what? (Score:5, Interesting)
We've known for decades that there are many mechanisms for regulating what cells produce. This regulation happens at all stages of protein synthesis, from unwinding the DNA from the chromatin to excreting it outside the cell. Methylation of the promoters is merely an example of this regulation. It is not changing your genetic code and making you a mutant. It is a simple "on/off" switch, no different from having a protein recognize a particular sequence on the promoter and sticking to it. And, of course, no one should be surprized at the blindingly obvious finding that exercise regulates expression of genes related to metabolism.
All this research is "exciting" only because it identifies the regulation pathway and thereby opens the possibility of direct intervention in it. Soon there might be drugs that let you sloth around on the couch watching TV all day long, while making the body think it has been working out eight hours a day. And maybe these (very expensive) drugs may even succeed at intervening in all the places regular exercise does, from growing your muscles, to reducing fat deposits, to increasing blood supply throughout the body. Then all those slobs that are dying in droves today would suddenly become healthy (and broke) hardbodies, who will delight in stuffing lockers with the laid off nerds who created those drugs (and were no longer needed thereafter). Yes, nerds like you, dear Slashdot reader. And oh, how you'll cry! And oh, how I'll say I told you so.
Re:Exercising easier? Really? (Score:4, Interesting)
First off, sugar's affect on metabolism is not linear. Ingesting a little sugar may increase the body's caloric need above the sugar's caloric content. Ingesting a lot of sugar definitely does not. Otherwise a mountain dew would be some unbelievable drug with lethal consequences.
Secondly, sugar comes in many forms, and those forms are packaged in various substances. No substances will have exactly the same affect on the body as another. Getting to the sugar in a sugar pill may be the cause of the increased caloric need while getting to the sugar in a mountain dew requires almost no change in caloric need.
Thirdly, bodies digest substances differently based on state. If I've been to the gym for an hour everyday for a year, my body won't notice much difference between the sugar pill and nothing at all. If my metabolic rate is effectively zero though, the sugar pill can have notice effects, as any ingested substance can.
Re:How can this be possible? (Score:4, Interesting)
As far as I know, there is nothing specific you can eat that is proven to boost your metabolism.
Nonsense. A dose of something like, say, 2,4-Dinitrophenol will absolutely increase your metabolic rate. Quite dramatically, and potentially to the point of lethal hyperthermia. On a side note, given DNP's effect on muscular intracellular Ca++ levels, I suspect it could have a demethylating effect similar to that obtained with caffeine used.
Re:Translation? (Score:4, Interesting)
As requested, I put a car-related analogy here [slashdot.org]. Since you technically asked a slightly different question, though, I'll give you a computer analogy to round things out.
Imagine you had an incredibly weird job scheduler that evaluated a huge probabilistic boolean expression, and then ran a given program afterwards if the expression evaluated to true. Then imagine that it ran this check several million times per second, and that all of the programs currently running had access to all of the variables used by all of the conditions, and could change them at any time. This is, essentially, how the cell decides what genes to express normally. No gene is ever expressed with 0% probability or 100% efficiency.
Methylation is like commenting out individual lines of code. An effect similar to block comments—with the same hilarious consequences if you make a typo in the end tag—is produced by another mechanism called an intron. We don't have to worry about this for the time being. Typically methylation applies to the header of a gene to prevent it from ever getting expressed (and to save on methyl groups) and the whole gene isn't methylated out.
The other thing you need to know about biology is that 'running' a program actually consists of copying a sequence of 6-bit numbers and then sending that copy to a synthesizer, which maps those 6-bit numbers onto a list of 20 small nanobot parts, and produces a string of these parts glued together. (3 of the 64 numbers are reserved for a special fake robot part adapter that causes the synthesizer to break apart, effectively stopping the synthesis.) The copy of the sequence used by the synthesizer also has a special header tag and a magic number, and most of the time the synthesizer is so lousy that it skips over it and just ejects the transcript completely. Some really strong header tags use sticky numbers to try and counteract this by slowing it down. Finally, the string of parts assembles itself by exploiting quantum electric effects that we still don't fully understand.
This, for fairly obscure reasons, is called the Central Dogma. The only actual part of the above that's metaphorical is the claim that there are variables—in fact, it's actually nanobots that physically attach themselves to the DNA. They're not very good at sticking, though, so it's a fair gamble as to whether or not they'll apply at a given moment. (Also, the nanobots are really called proteins, the synthesizer is called a ribosome, the 6-bit numbers are called codons, the robot parts are called amino acids, synthesis is called translation, the 'sticky numbers' are called Kozak sequences, and the magic number is "AUG".)
In this case, the body is uncommenting a handful of specialized genes that it only wants turned on when lots of resources are available. We believe that the caffeine tells the body to speed up usage of one particular common resource, called ATP. You don't want every gene in the body to be unmethylated, though: most of them only work properly in one type of cell in one part of the body, and many of them don't even work properly because they've fallen into severe disrepair, or even been corrupted. Even these genes could be harmful under the wrong conditions—giving caffeine to someone who's starving to death will only make him or her starve faster.
I hope that helps!
(One question I used to get a lot from students doing work in single-celled organisms was how the body can tell which tissue is which. The answer is very elegant to a computer scientist, but baffling to a biologist who hasn't done specialized research: different arguments passed in recursive calls. When the parent stem cell splits in two, it's programmed to turn variables on and off depending on which half the chromosomes are in.)