Running Science

by Owen Anderson

  Similarly, research reveals that deactivation of a gene that produces myostatin, a chemical that thwarts muscle growth, results in the appearance of so-called super mice with about twice the normal amount of muscle mass. Another strip of DNA, the PPAR-delta gene, has a profound impact on mitochondrial production inside muscle cells (mitochondria are intracellular sites of energy creation, and research has linked heightened mitochondrial density with increased resistance to fatigue). Manipulation of the PPAR-delta gene in scientific inquiries has resulted in the creation of what are called marathon mice that can run about 70 percent longer and 90 percent farther than unaltered mice. Though the same results may or may not occur in humans, the theory of a gene as a magic bullet is advanced by such investigations.

  Testing the Nature-Versus-Nurture Hypotheses

  Concluding that genetic differences are the paramount factor underlying endurance-performance success is premature, however. In many cases, further analysis of the actions of specific genes reveals that the effects are not always consistent or that the genes that seem to have the biggest impact on performance are not necessarily monopolized by—or even present in—groups of high-performing endurance runners. Many other possibilities for the determination of performance are apparent. Training, or nurture, is certainly one of those elements; even the biggest advocate of nature over nurture must admit that training plays a large role in determining what the race clock reveals when a runner crosses the finish line. In the East African case, there is considerable evidence that Kenyan training differs dramatically from the training carried out by endurance runners in other parts of the world.14

  In fact, training is commonly considered to be the most important extrinsic, or environmental, factor affecting performance. Scientists use two techniques in their attempts to disentangle environmental and genetic effects and thus provide answers to the debate over nature versus nurture. One method is to look for evidence of patterns of variation in performance variables (for example, O2max or responsiveness to training) in a population. As long as there is variation for a given performance-related trait, estimating the relative contributions of environmental and heritable (genetic) factors to this variation is possible.

  This kind of work can be carried out with families. For example, maximal aerobic capacity (O2max), a physiological variable linked with exercise capacity, can be studied in large populations containing family groups. If O2max varies considerably between families but very little among family members, there is evidence that O2max is strongly determined by genetic factors because individuals in the same family tend to have nearly identical O2max values and are very similar genetically. If O2max varies just as much within families as it does between families, then genetic factors would appear to play a small role in determining O2max. The O2max of one’s father, mother, or sibling is not necessarily closer to one’s own maximal aerobic capacity than the O2max of the unrelated stranger living across town.

  Geneticists interested in performance try to establish in their studies what is called heritability of a trait, or H2. Without delving deeply into the math, it is possible to say that H2 is nothing more than the ratio of genetic variance to total phenotypic variance for a specific performance variable. Genetic variance refers to the diversity in a variable, such as O2max, that is produced by actual genetic differences, while phenotypic variance is the total measured heterogeneity (maximal amount of the variable possible) in a variable. For math buffs, the equation for heritability follows:

  H2 = Vg/Vp

  with Vg being the variance due to genetic factors and Vp the total phenotypic variance.

  If research reveals that H2 is something small, for example .1, then one can conclude that genes are playing a small role in setting up the variance—the array of characteristics such as aerobic capacity—that one observes in a population. On the other hand, if H2 is close to 1.0, then genes are playing a huge role.

  The rest of the variation above and beyond H2 (what geneticists call Ve/Vp, which is environmental variance divided by phenotypic variance) can be attributed to environmental factors, including training. Training can be subdivided into willingness to train, ability to train, opportunity to train, and quality of the overall training program. Additional environmental factors can be cultural in nature (e.g., diet, attitude toward running) or geographic (e.g., altitude, temperature, humidity, wind, running surface).

  Research using the heritability model has revealed that heritable, or genetic, factors are important but not exclusive determinants of several physiological variables that contribute to success in endurance running. One investigation found that 48 to 74 percent of baseline submaximal aerobic performance—the ability to sustain continuous exercise without previous training—could be attributed to genetic factors. The same inquiry discovered that responsiveness to training—the degree to which aerobic capacity improved as a result of a specific training stimulus—had an H2 of 23 to 57 percent.15

  An additional scientific study detected an H2 of 38 to 87 percent for maximal aerobic capacity, O2max, a traditional measure of running fitness.16 Another inquiry estimated that the degree to which O2max increases in response to exercise has a heritability of about 47 percent, and that anaerobic, or lactate, threshold has a heritability of 55 to 80 percent.17

  In an important investigation, the performance of mothers, fathers, daughters, and sons on exercise bikes was measured in 86 nuclear families. O2max turned out to have a heritability of about 51 percent in these individuals. The other 49 percent of the variation might be accounted for by diet, attitude toward exercise, daily activity pattern, or other factors.18

  Taken together, these wide-ranging values for heritability tell runners and their coaches that genetics do play a role in performance; after all, heritability does not drop below 23 percent and can be as high as 87 percent. This is hardly a shocking discovery, however, and it contains no practical information for a runner or coach. It is impossible for an individual to tell to what extent his or her performance is based on genes rather than environment, nor would such knowledge have a significant impact on training, which should always be formulated to be the best, most up-to-date, and most scientifically based regardless of underlying genetic constitution.

  Note also that heritability studies have trouble truly differentiating between genetic and environmental factors. Family members share not only their genes but also their environments, which undoubtedly include important dietary and psychological factors. Thus, some unknown portion of the genetic variance H2 is probably environmental in nature.

  How to Determine O2max

  O2max, or maximal aerobic capacity, is a traditional measure of endurance fitness. Usually expressed in milliliters of oxygen per kilogram of body weight per minute (ml·kg-1·min-1 as expressed in scientific terms), O2max reflects the heart’s ability to pump oxygen to the muscles and the muscles’ capacities to use oxygen to provide the energy required for running. O2max is usually measured on a treadmill in an exercise laboratory, with a subject warming up and then progressing to increasingly quicker treadmill speeds or higher treadmill inclinations until a plateau or near plateau in oxygen consumption rate is reached, reflecting underlying heart, muscle, or neuromuscular limitations. This plateau is then termed O2max. Table 1.2 provides varying fitness levels for aerobic capacity in females and males.

  Conclusion

  The heritability studies referred to in this chapter suggest that an individual’s capability for distance running is determined by both genetic and environmental factors, and the exact proportion of influence is unknown. This is certainly logical, because it is unlikely that a runner’s performance characteristics would be completely unmarked by either genetic or environmental elements. However, the heritability research has not been carried out with elite athletes, and it does not answer the basic question of whether Kenyan and other African runners enjoy a genetic superiority that causes Vg (i.e., the genetic contribution to performance) to be maximized. To explore these ideas f
urther, chapter 2 discusses a second approach to the genetics of running: an analysis linking specific genes with improvements in performance. Chapter 3 then takes a close look at whether a unique genotype is necessary for achieving elite status as a runner.

  Chapter 2

  Genes That Influence Performance

  Most runners and coaches realize that genetic factors affect performance. What is less commonly realized is that heredity can act in two completely different ways. First, specific genes or gene combinations can make certain individuals inherently more fit than others, even in situations in which no training has been carried out. Two sedentary individuals plucked at random from the street would be unlikely to have the same fitness level: One might have a stronger heart, a higher O2max, or reduced perceptions of fatigue during exercise, and these differences could be related to genetic makeup. If the non-trained duo agreed to engage in a 5K run, actual performance would hinge on the inherent physiological variations.

  Second, some genes or combinations of genes control the way in which individuals respond to training.1 Some novice runners adapt dramatically to their training protocols, improving maximal aerobic capacity (O2max) by as much as 80 percent over an 8-week period of serious training. Other, less-fortunate individuals might inch O2max up by just 5 to 10 percent as a result of the same strenuous training. Finally, some individuals do not seem to respond to training at all; their physiological variables related to performance remain stagnant, even after weeks of hard work.2 Thus, in a group of untrained individuals, variable responses to training can create situations where individuals who are inherently less fit than others can move far ahead of those who were originally more fit.

  Both gene-related inherent fitness and gene-related responsiveness to training play roles in determining ultimate performance potential. Of course, quality of training is also important, but it is a nongenetic factor—unless a gene exists that codes for the ability to set up smart training!

  Gene-Related Responsiveness

  Researchers have identified a gene that influences how runners respond to training; it is a particular variant of the human angiotensin-converting enzyme (ACE) gene. Having the I variant, or I allele (an allele is simply one possible form of a gene), of the ACE gene tends to improve an individual’s ability to adapt to endurance training,3 perhaps by enhancing economy of movement.

  Every runner has two ACE genes: Roughly 50 percent of runners have the I allele along with another variant of the ACE gene called the D, or short, allele; 25 percent have two I alleles, and the other 25 percent have two shorts in their ACE chromosomal slots. In one investigation, individuals with two copies of the I allele gained more muscle mass and lost more body fat during 10 weeks of intensive physical training than subjects who had two copies of the short allele or one copy of each.4

  In a separate study, 58 men underwent an 11-week program that involved interval training on an exercise bike; 35 of these men had two I alleles, while 23 had two short alleles.5 Prior to and after the training period, the researchers calculated the delta efficiency of exercise for each subject. This variable represents the efficiency with which muscles are working; it is the ratio of the change in work performed per minute to the change in energy expended in the same amount of time expressed as a percentage. Delta efficiency reflects the fact that if a runner can increase rate of work per minute (i.e., muscular power output and thus running velocity) without a large upswing in energy expenditure, the runner is operating efficiently. In contrast, a runner will have a low delta efficiency if energy consumption soars when running speed is increased.

  Before the 11 weeks of training began, delta efficiency was the same for both groups of men: about 25 percent, which is average. At the end of the training period, delta efficiency had improved by almost 9 percent for the men with two copies of the I allele but had remained stagnant for the subjects with two short alleles.

  Gene-Related Inherent Fitness

  One of the key—but often overlooked—adaptations that runners’ bodies make to training involves the responsiveness of blood vessels. When a previously sedentary individual runs regularly for a couple of months, many arteries, arterioles, and capillaries relax more easily during exercise, increasing the rate of blood flow—and thus oxygen and fuel—to the muscles. At least some of this arterial expansiveness is mediated by the chemical nitric oxide, which is released by cells lining the arteries. Nitric oxide does not just dilate arteries; it can also prolong vasodilation, helping to ensure that large amounts of blood will flow toward the muscles during extended exertion.

  Exercise training increases the production of nitric oxide within arteries, and the presence of two I alleles seems to spike this nitric oxide synthesis even more. In effect, the presence of two I alleles permits the muscles of endurance-trained runners to have more blood. Dr. Hugh Montgomery, the lead scientist in the 11-week study discussed previously, also believes that I alleles may have profound metabolic influences within muscle cells, perhaps improving the efficiency of fuel selection, uptake, and use during exercise.6

  Scientific studies reveal that runners with two copies of the I allele tend to gravitate toward longer-distance running rather than sprints and middle-distance events. I allele frequency actually increases with the distance run: For example, a genetic survey of Olympic-standard runners detected a higher frequency of the I allele among those athletes competing at 5K or longer compared with runners competing at 3K, 1500 meters, and other shorter distances.7 Exactly the same situation prevails with competitive swimmers: Long-distance swimmers have higher frequencies of the I allele and short-distance competitors have higher frequencies of the short allele.7

  Testing the Hypothesis of Kenyans’ Superior Adaptation

  As a group, Kenyan distance runners are superior to competitors from the rest of the world. One theory attempting to explain this phenomenon has suggested that Kenyan runners have genetic constitutions that make them better responders; that is, they respond to a specific level of training with a greater extent of adaptation compared with runners from other countries. In line with this hypothesis, one study found that physically active adolescent Kenyan boys had maximal oxygen uptakes that were 30 percent higher than others of a similar-age cohort who were inactive, even though the active boys were not carrying out any systematic running training; their activities consisted of farm work, jogging back and forth to school, and walking, among others.8 A 30 percent response to general activity is considered extremely large. It is assumed that the adaptation would be even greater if serious training were undertaken since it is typical for maximal aerobic capacity to advance by 15 to 25 percent as a normal response to structured training.

  Although Kenyan runners dominate the world of distance running today, they do not have a monopoly on genes linked with high performance.

  Bennett Cohen/Icon SMI

  To find out if Kenyans are programmed to be better responders, Henrik Larsen and his colleagues from the Copenhagen Muscle Research Centre and the University of Copenhagen traveled to Kenya to work with 24 teenage Kenyan males.9 All these young men (average age = 16.5 years) belonged to the Nandi subtribe of the Kalenjin tribal group within Kenya; none had been engaged in systematic endurance training prior to beginning the study. The young Kenyans were classified as “town boys” or “village boys” by Larsen and his cohorts. The town runners were recruited from the city of Eldoret in the western part of Kenya. In contrast, the village runners were found at the Kamobo Secondary School located about 50 kilometers southwest of Eldoret; these subjects lived in a highly rural area within a 4-kilometer radius of the school. In total, there were 10 town runners and 14 village runners.

  When the research began, the village runners had an average O2max of 56 ml kg-1 min-1, which was significantly higher than the 50.3 ml • kg-1 • min-1 registered by the town runners; this difference was probably due to the higher natural activity levels of the villagers. All 24 young men subsequently completed 12 weeks of endurance training. D
uring the first 5 weeks, training frequency advanced from two to four workouts per week, weekly training distance moved from 8 to 28 kilometers, and actual running intensity increased from 70 to 80 percent of O2max. Over the last 7 weeks, the weekly training consisted of four workouts, 28 kilometers of total running, and a constant intensity of 80 percent of O2max (about 87 to 88 percent of maximal heart rate). Since the village runners were fitter than the town runners, 80 percent of O2max for the villagers corresponded with a faster training pace. Indeed, the village runners trained at an average speed of 13.8 kilometers per hour (about 7 min per mi), compared with 12.4 kilometers per hour (approximately 7:47 min per mi) for the town runners.

  Both the town and village runners benefited significantly from the training, and their responses were remarkably similar. For example, after the 12 weeks of training, mean heart rate at a submaximal running speed of 9.9 kilometers per hour declined from 170 to 159 beats per minute in the village runners and from 172 to 160 beats per minute for the town runners. Additionally, blood lactate concentration and plasma ammonia levels (an indicator of protein breakdown during exercise) dropped similarly for both groups, and running economy improved by a similar amount for both the village and town runners.

  The only real difference in training response between the two groups concerned O2max, which tended to increase more for the town runners compared with the village runners. For the town runners, the increase in O2max was 10 percent compared with a 5 percent increase for the villagers. This difference was just shy of being statistically significant, but there is nothing particularly notable about it. The gain in O2max that is made during training is related to the magnitude of O2max at the beginning of the training period: Individuals with low O2max values tend to achieve robust expansions of maximal aerobic capacities, while those with higher O2maxs tend to make smaller improvements.10, 11 Over the 12 weeks, the town runners increased O2max from 50 to 56 ml • kg-1 • min-1; the village runners increased O2max from 56 to 59 ml • kg-1 • min-1. Although the villagers increased O2max by a smaller amount, they were still aerobically fitter than the Eldoret runners, and so they performed better during a final 5K, achieving an average time of 18:25 minutes (best time was 16:16) versus 20:15 minutes for the town runners (best was 18:40).