Friday, October 14, 2016

Use it or lose it: the economics of exercise adaptation

Have you ever wondered why fitness is so hard to get? Why you have to run so many miles and lift so many things to gain endurance, speed or strength? And why these fitness gains diminish so quickly after even just a few days away from training? To extend the question to all animals: Why aren't creatures simply endowed, genetically, with the physical abilities they'll need in life?

Exercise capacity in animals is not simply programmed by genes.  Like all other genetically influenced traits, the physiological components of fitness-- things like muscle size, mitochondrial density, stroke volume of the heart, etc etc etc-- are encoded by genes but these genes are only expressed in the right environment.  Without an exercise stimulus, these genes are not expressed.  To a biologist, this is a classic illustration of the principle that genes don't work in a vacuum.  (Genes evolve as part of an entire organism, and the organism is part of a complex ecosystem.)

Evolutionary biology has a pretty good explanation for the Use It Or Lose It nature of fitness: it's a matter of energetic economics.  Remember that natural selection is blind to everything other than reproductive success.  In other words, only genes and traits that contribute to increased reproduction, directly or indirectly, should evolve to become more common.  This is evolutionary biology dogma and I'm not suggesting anything new here (or at any point yet in this post).  It makes sense that animals have genes that can, in the right conditions, make them fast, strong, and have great endurance-- being strong and fast can help get food or avoid being food, and this will help you have more offspring.  But because the physiological components of fitness require energy to produce and maintain, it also makes sense that animals have evolved highly-sensitive mechanisms for producing these adaptations, and that they are no longer maintained when you become sedentary again.  An antelope's aerobic capacity will develop as it runs more, much as yours will too; but if the environment doesn't require much running, it makes sense to spend that metabolic currency elsewhere, on things that will more directly lead to increased reproduction, such as a stronger immune system (and indeed intense exercise does compromise the human immune system).  In short: There's only so much energy to go around and your body will only spend it on exercise adaptations if it's apparent that they're necessary.

Some adaptations to endurance exercise, off the top of my head, that all incur a metabolic cost to produce and maintain:
  • Increased muscle mitochondrial number and size
  • Increased muscle oxidative enzymes
  • New blood capillaries to feed muscle
  • Bone formation- thicker cortical bone, increased thickness of trabecular bone
  • Increased thickness of heart muscle, heart overall grows in size
  • Increase in lung capacity
  • Increased production of red blood cells
Adaptations to shorter, more intense exercise, such as strength and sprint training:
  • Increased muscle size (muscle is a very expensive tissue!)
  • Increased muscle recruitment by the nervous system (ability to engage more muscle tissue)
...and, endurance and strength adaptations will often diminish each other.  Endurance training limits the muscle growth response triggered by strength training.  Muscle fibers change which proteins they express and take on characteristics useful to only strength or endurance, not both.  This seems to be true for mammals in general and not unique to humans.

To me, the observation that humans have the capacity to be great endurance athletes, but that our bodies will only realize this capacity with a sustained exercise stimulus, is evidence for two profound truths about our evolution.  First, our ancestors lived on the margins of energy balance, at least at key points in our evolution; that is, they barely scraped by, energetically speaking.  Second, endurance was part of our ecological niche, our survival strategy. Natural selection favored those who could develop endurance when they needed it and conserve every pithy calorie otherwise.  Further evidence for this lies in our body fat: we can stores prodigious amounts, more than any other primate, and it's both a great starvation buffer (energy saved for lean times) and great endurance fuel.  Of course, being energetically thrifty and only producing exercise adaptations when necessary is not unique to humans- these genetic traits evolved in earlier animal groups-- but humans seem to have elaborated on this trait.  And, I'd like to say that non-running animals don't respond as robustly to exercise as running animals do (we do know they have lower aerobic capacity relative to body mass), but I'm not sure this research has been done.  If you see any, please send that along!

The fairly recent discovery that some people respond more vigorously to exercise than others can inform this topic.  (NYT article here , though the Wellness/Phys Ed section of the Time really chafes me.)  About 35% of people fall outside of the normal curve for exercise adaptation-- 15-20% are "non responders", getting little or no gain in aerobic capacity, and 15-20% are "super-responders", reaping greater aerobic awards than others.  As with other genetic traits that have a bell-curve like distribution, this is evidence that natural selection has worked against both extremes-- the non-responders and the super-responders alike.   In evolutionary biology this is called "stabilizing selection"-- the middle phenotype (physical trait) is most common as the extremes are selected against.  So even though being a super-responder might be great now, as a person trying to get fit or as a competitive athlete (and I suspect that many elite athletes are super-responders), it clearly wasn't so great in our past, or this phenotype would be way more common.

My attempt at visualizing the stabilizing selection that has acted on the 11 genes influencing aerobic exercise response.

This makes sense given what we discussed above.  Early humans who thanks to the genetic lottery were unable to increase their aerobic capacity would have had less reproductive success-- why, exactly, we're not sure, because this brings us back to the big unanswered question of "what exactly did humans need endurance for?", a question that drives me and will for many years.  (The answer surely has to do with covering ground to find food.)  Genes influencing super-responding, too, have been selected against and are now fairly uncommon because adapting too vigorously, or producing adaptations at too low a stimulus threshold, would expend more metabolic energy than is necessary, pushing these folks closer to the business-end of energy balance and therefore compromising their immune systems and generally putting them at all sorts of disadvantages.

Evolution does not have the benefit of limitless traits upon which to act and select.  Instead, it is a ceaseless process of selection between only a handful of available genes; and then the next handful; and then the next.  But this process does favor traits that are even 1% more advantageous than the alternatives, until at some point you end up with a pretty good solution, with continued selection against the other alternatives (above, the super- and non-responders).  But of course, given our modern lifestyle, selection for the ideal exercise response is surely relaxed, and who knows what this nice bell curve graph would look like in 10,000 years?....


Tuesday, July 19, 2016

Of Mice and Men: How does the biology of running evolve?

Mobility as an Emergent Property of Biological Organization: Insights from Experimental Evolution

Evolutionary Anthropology just published a fantastic article (linked above, full text) summarizing 20 years of research with mice selectively bred to run.  That is, mice that voluntarily run more distance per day have been bred together for generations, producing mice that are biologically better at running, and willingly run longer each day, than other mice.  If you're wondering how this is informative or productive: selective breeding is used by scientists all the time to understand how real evolution occurs and how biology changes as particular traits become more common.  Selective breeding is a lab-controlled simulation of real selection-- natural selection-- that occurs in nature.  In this case, these studies have produced some fascinating insights into how evolution produces a biologically-equipped mammalian runner.  As we are also mammals, these mice studies raise all kinds of testable questions regarding the evolution of human running. 

For anyone not wishing to chew on the review article above (though it is very digestible, I think, perhaps even for non-science folks), here I'll summarize the significant differences that have been observed in running-bred vs. non-running mice. (Note that these closely, but do not entirely, follow the bullet points in the article.)

Mice bred to voluntary run more have led to generations of mice that, well, run more.  (Mostly because they run faster, actually.)

What mice tell us about the evolution of running

1. Running is compelled by biology.  You and I might consciously decide to head out the door for a run because we know it will make us feel good.  Or lose weight. Or whatever.  Other cursorial (running) animals aren't motivated by this foresight but rather by unconscious drives.  These drives (which we have too! Check out "Wired to Run"-- your brain makes pot-like chemicals when you run) directly motivate animals to move.  They have likely evolved because running serves some survival purpose.  In mice, I have no idea what that could be, but in dogs and wolves, it's food acquisition: an animal that is motivated to run covers more territory and finds more food.  Hence, those genes are passed on more successfully than couch-potato dogs, and so evolution goes.  We know that the drive to run in the running-bred mice is genetic and biological, and not learned, because it is present early in a running-bred mouse's little life, before they have had a chance to get used to a running wheel.  In short: the urge to run can be genetic and biological, and therefore it can evolve through natural selection.

What are some of the mechanisms of this biology that motivates animals to run?  Well, in humans and dogs, it's the aforementioned endocannabinoids (see link above).  In mice it seems to be a change in how the brain chemical dopamine functions.  Here's an example of "convergent evolution"-- similar solutions arising independently in different animal species to solve the same problem. 

2. Selection for increased motivation to run, and running ability, comes with lots of biological changes.  Some are mentioned above-- changes in reward pathways in the brain which encourage animals to run.  In wolves and dogs--who clearly have an excellent evolved running capability- certain biological traits have an obvious positive effect on running performance: muscle composition, leg length, etc.  But the selective breeding experiments with mice demonstrate how some of these characteristics can evolve, or change, from a baseline population of non-running-adapted animals.  Running mice, over generations, developed a higher VO2-max (oxygen carrying capacity) than non running mice; decreased body size, leading to more efficient running; decreased calf muscle size, which is good for endurance running because it reduces the weight lifted with each stride; increased midbrain size (possibly to increase the reward pathways discussed earlier, or to aid in coordination); increased surface area in the leg joints, good for shock absorption; and intriguingly, differently-shaped semicircular canals, which are structures in the head important for balance and thought to be essential for frequent and effective endurance running.  I say "intriguing" because this last observation is also seen in the fossil record early in our genus, as are many of the other evolved traits of the running-bred mice.  It would be rash to directly apply observations of artificial selection in mice to human evolution, but these results (to me) point to things we should look for in human evolutionary history when testing hypotheses about whether, when and how humans evolved to run.  And the fact that we see similar traits in humans is tantalizing. The takeaway: selection for increased running performance does indeed lead to genetic, biological changes that improve running ability.

3. Evolved running ability comes at a cost, and is constrained by evolutionary "trade offs".
I often joke that the better I get at running, the worse I get at everything else.  There is truth in this at an evolutionary level: traits that enhance one thing will likely have a negative (or sometimes positive) impact on other things.  A great example is Herman Ponzter's observation that, in cursorial mammals, hind limb length has evolved for running efficiency, but only to a point: super long limbs would cost a lot to grow during development and would decrease sprinting speed far too much.  When evolutionary costs outweigh benefits, a trait will cease to become more pronounced over time- it will have reached an equilibrium of sorts, a compromise.  Similar constraints are observed in the "evolution" of our running mice.  Their reduced calf musculature makes them slower sprinters, and in a natural setting with predators, natural selection would likely work to reduce this calf-shrinking trend, despite any advantages it might convey for endurance running, which for mice would be almost nothing-- they are not endurance runners, let's remember.  (Interestingly, as an aside, this trait is caused by a single allele for a single gene. Also interesting is that the size and location of calf musculature in human runners has a significant effect on running economy.) This trade-off between endurance and speed surely limits the endurance-running adaptations that any cursorial animal develops.  Perhaps humans too, though sprinting can't have been especially helpful to us in my opinion, because even Usain Bolt would have trouble outsprinting an African carnivore.  

Anther tradeoff observed in mice: increased corticosterone levels in the running-adapted mice is helpful in that it increases fuel availability for muscles and encourages running behavior, but decreases immune function, inhibits growth, and may lead to depression (sad little mice). The first two effects, if at play in the evolution of any running species in a real setting, would incur significant fitness penalties and would therefore be highly constrained. 

Finally, like any other complex trait, endurance running motivation and ability is influenced by many genes, some of which have many different jobs and effects.  (This is called "pleiotropy".) This helps explain the trade-offs mentioned above, but it also explains some of the stranger results found in the mice study, like the observation that running mice "build smaller nests in their home cages, display greater predatory aggression towards crickets, and have a slightly altered finger-digit ratio".  The latter is also found in humans to predict athletic and running ability.  Like the other weird observations, finger ratios have no direct effect on running performance, in humans or mice.  Rather, they are influenced by similar genes, like the ones encoding the hormone testosterone.  Genetic changes that evolve to enhance running ability also have other weird side effects that will simply come along for the ride, and won't be selected against unless they are super deleterious.

Unfortunately (or maybe fortunately for me) there are still very few researchers asking evolutionary questions about human running, so it will be years before some of these insights are applied to humans. 

Wednesday, July 13, 2016

1.5 million year old footprints.... Ileret Kenya demonstrate a modern human foot in Homo erectus.

Figure 1

I met the lead researcher in San Francisco in 2015 and I am floored by the methods he uses to infer so much from these amazing prints.  A modern foot with a longitudinal arch is also a foot capable of efficient running...