Muscle,Genesand Athletic Performance

The cellular biology of muscle helps to explain why a particular athlete winsand suggests what future athletes might do to better their odds

by Jesper L. Andersen, Peter Schjerling and Bengt Saltin

Copyright 2000 Scientific American, Inc.

On your marks!” Ahush falls as 60,000pairs of eyes are fixedon eight of the fastestmen on earth. Thedate is August 22,1999, and the run-

ners are crouched at the starting line ofthe 100-meter final at the track-and-fieldworld championships in Seville, Spain.

“Get set!” The crack of the gun echoesin the warm evening air, and the crowdroars as the competitors leap from theirblocks. Just 9.80 seconds later the win-ner streaks past the finish line. On thisparticular day, it is Maurice Greene, a25-year-old athlete from Los Angeles.

Why, we might ask, is MauriceGreene, and not Bruny Surin of Canada,who finished second, the fastest man onearth? After all, both men have trainedincessantly for this moment for years,maintaining an ascetic regimen basedon exercise, rest, a strict diet and littleelse. The answer, of course, is a complexone, touching on myriad small detailssuch as the athletes’ mental outlook onrace day and even the design of theirrunning shoes. But in a sprint, depend-ent as it is on raw power, one of thebiggest single contributors to victory is physiological: the muscle fibers inGreene’s legs, particularly his thighs,are able to generate slightly more pow-er for the brief duration of the sprintthan can those of his competitors.

Recent findings in our laboratories andelsewhere have expanded our knowledgeof how human muscle adapts to exerciseor the lack of it and the extent to whichan individual’s muscle can alter itself tomeet different challenges—such as thelong struggle of a marathon or the ex-plosive burst of a sprint. The informa-tion helps us understand why an athletelike Greene triumphs and also gives usinsights into the range of capabilities ofordinary people. It even sheds light onthe perennial issue of whether elite run-ners, swimmers, cyclists and cross-coun-try skiers are born different from therest of us or whether proper trainingand determination could turn almostanyone into a champion.

Skeletal muscle is the most abundanttissue in the human body and also one ofthe most adaptable. Vigorous trainingwith weights can double or triple amuscle’s size, whereas disuse, as in spacetravel, can shrink it by 20 percent in twoweeks. The many biomechanical andbiochemical phenomena behind theseadaptations are enormously complex,

but decades of research have built up areasonably complete picture of howmuscles respond to athletic training.

What most people think of as a mus-cle is actually a bundle of cells, alsoknown as fibers, kept together by colla-gen tissue [see illustration on pages 50and 51]. A single fiber of skeletal muscleconsists of a membrane, many scatterednuclei that contain the genes and lie justunder the membrane along the length ofthe fiber, and thousands of inner strandscalled myofibrils that constitute the cy-toplasm of the cell. The largest andlongest human muscle fibers are up to30 centimeters long and 0.05 to 0.15millimeter wide and contain severalthousand nuclei.

Filling the inside of a muscle fiber, themyofibrils are the same length as thefiber and are the part that causes the cellto contract forcefully in response tonerve impulses. Motor nerve cells, orneurons, extend from the spinal cord toa group of fibers, making up a motorunit. In leg muscles, a motor neuron con-trols, or “innervates,” several hundredto 1,000 or more muscle fibers. Where

extreme precision is needed, for exam-ple, to control a finger, an eyeball or thelarynx, one motor neuron controls onlyone or at most a few muscle fibers.

The actual contraction of a myofibrilis accomplished by its tiny componentunits, which are called sarcomeres andare linked end to end to make up a my-ofibril. Within each sarcomere are twofilamentary proteins, known as myosinand actin, whose interaction causes thecontraction. Basically, during contrac-

tion a sarcomere shortens like a collaps-ing telescope, as the actin filaments ateach end of a central myosin filamentslide toward the myosin’s center.

One component of the myosin mole-cule, the so-called heavy chain, deter-mines the functional characteristics ofthe muscle fiber. In an adult, this heavychain exists in three different varieties,known as isoforms. These isoforms aredesignated I, IIa and IIx, as are the fibersthat contain them. Type I fibers are alsoknown as slow fibers; type IIa and IIxare referred to as fast fibers. The fibersare called slow and fast for good reason:the maximum contraction velocity of asingle type I fiber is approximately onetenth that of a type IIx fiber. The veloci-ty of type IIa fibers is somewhere be-tween those of type I and type IIx.

The Stuff of Muscle

The differing contraction speeds ofthe fibers is a result of differences in

the way the fibers break down a mole-cule called adenosine triphosphate in themyosin heavy chain region to derive the

energy needed for contraction. Slowfibers rely more on relatively efficientaerobic metabolism, whereas the fastfibers depend more on anaerobic metab-olism. Thus, slow fibers are importantfor endurance activities and sports suchas long-distance running, cycling andswimming, whereas fast fibers are key topower pursuits such as weight liftingand sprinting.

The “average” healthy adult hasroughly equal numbers of slow and fast

Scientific American September 2000 49Muscle, Genes and Athletic Performance

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WORLD-CLASS SPRINTER BRIAN LEWIS of the U.S. (opposite page) has a largerproportion of so-called fast muscle fibers in his legs than a marathoner or an extremeendurance athlete does. Fast IIx fiber contracts 10 times faster than slow type I fiber,and type IIa lies somewhere in between.

Copyright 2000 Scientific American, Inc.

fibers in, say, the quadriceps muscle inthe thigh. But as a species, humansshow great variation in this regard; wehave encountered people with a slow-fiber percentage as low as 19 percentand as high as 95 percent in the quadri-ceps muscle. A person with 95 percentslow fibers could probably become anaccomplished marathoner but wouldnever get anywhere as a sprinter; the op-posite would be true of a person with19 percent slow fibers.

Besides the three distinct fiber types,there are hybrids containing two differ-ent myosin isoforms. The hybrid fibersfall in a continuum ranging from thosealmost totally dominated by, say, theslow isoform to fibers almost totallydominated by a fast one. In either case,as might be expected, the functionalcharacteristics of the fiber are close tothose of the dominant fiber type.

Myosin is an unusual and intriguingprotein. Comparing myosin isoformsfrom different mammals, researchershave found remarkably little variationfrom species to species. The slow (type I)myosin found in a rat is much more sim-ilar to the slow isoform found in hu-mans than it is to the rat’s own fast myo-sins. This fact suggests that selective evo-

lutionary pressure has maintained func-tionally distinct myosin isoforms andthat this pressure has basically preservedparticular isoforms that came aboutover millions of years of evolution.These myosin types arose quite early inevolution—even the most ancient andprimitive creatures had myosin isoformsnot terribly different from ours.

Bulking Up

Muscle fibers cannot split them-selves to form completely new

fibers. As people age, they lose musclefibers, but they never gain new ones [seebox on page 54]. So a muscle can be-come more massive only when its indi-vidual fibers become thicker.

What causes this thickening is the cre-ation of additional myofibrils. The me-chanical stresses that exercise exerts ontendons and other structures connectedto the muscle trigger signaling proteinsthat activate genes that cause the musclefibers to make more contractile pro-teins. These proteins, chiefly myosin andactin, are needed as the fiber producesgreat amounts of additional myofibrils.

More nuclei are required to produceand support the making of additional

protein and to keep up a certain ratio ofcell volume to nuclei. As mentioned,muscle fibers have multiple nuclei, butthe nuclei within the muscle fiber cannotdivide, so the new nuclei are donated byso-called satellite cells (also known asstem cells). Scattered among the manynuclei on the surface of a skeletal musclefiber, satellite cells are largely separatefrom the muscle cell. The satellite cellshave only one nucleus apiece and canreplicate by dividing. After fusion withthe muscle fiber, they serve as a source ofnew nuclei to supplement the growingfiber.

Satellite cells proliferate in response tothe wear and tear of exercise. One theo-ry holds that rigorous exercise inflictstiny “microtears” in muscle fibers. Thedamaged area attracts the satellite cells,which incorporate themselves into themuscle tissue and begin producing pro-teins to fill the gap. As the satellite cellsmultiply, some remain as satellites on thefiber, but others become incorporatedinto it. These nuclei become indistin-guishable from the muscle cell’s othernuclei. With these additional nuclei, thefiber is able to churn out more proteinsand create more myofibrils.

To produce a protein, a muscle cell—

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MUSCLE consists of cells full of strands called myofibrils, whichare in turn made up of contractile units called sarcomeres. Thekey components of sarcomeres are two filamentary proteins,actin and myosin. These protein molecules slide over one anothertelescopically as the sarcomere contracts and uncontracts.

50 Scientific American September 2000

CONNECTIVETISSUE

Copyright 2000 Scientific American, Inc.Copyright 2000 Scientific American, Inc.

like any cell in the body—must have a“blueprint” to specify the order in whichamino acids should be put together tomake the protein—in other words, to in-dicate which protein will be created. Thisblueprint is a gene in the cell’s nucleus,and the process by which the informa-tion gets out of the nucleus into the cyto-plasm, where the protein will be made,starts with transcription. It occurs in thenucleus when a gene’s information (en-coded in DNA) is copied into a moleculecalled messenger RNA. The mRNA thencarries this information outside the nu-cleus to the ribosomes, which assembleamino acids into the proteins—actin orone of the myosin isoforms, for ex-ample—as specified by the mRNA. Thislast process is called translation. Biolo-gists refer to the entire process of produc-ing a protein from a gene as “expres-sion” of that gene.

Two of the most fundamental areasof study in skeletal muscle research—ones that bear directly on athletic per-formance—revolve around the way inwhich exercise and other stimuli causemuscles to become enlarged (a processcalled hypertrophy) and how such activ-ity can convert muscle fibers from onetype to another. We and others havepursued these subjects intensively in re-

cent years and have made some signifi-cant observations.

The research goes back to the early1960s, when A. J. Buller and John Ca-rew Eccles of the Australian NationalUniversity in Canberra and later MichaelBárány and his co-workers at the Insti-tute for Muscle Disease in New YorkCity performed a series of animal stud-ies that converted skeletal muscle fibersfrom fast to slow and from slow to fast.The researchers used several differentmeans to convert the fibers, the mostcommon of which was cross-innervation.They switched a nerve that controlled aslow muscle with one linked to a fastmuscle, so that each controlled the op-posite type of fiber. The researchers alsoelectrically stimulated muscles for pro-longed periods or, to get the opposite ef-fect, cut the nerve leading to the muscle.

In the 1970s and 1980s muscle spe-cialists focused on demonstrating thatthe ability of a muscle fiber to changesize and type, a feature generally referredto as muscle plasticity, also applied tohumans. An extreme example of this ef-fect occurs in people who have suffereda spinal cord injury serious enough tohave paralyzed their lower body. Thelack of nerve impulses and general dis-use of the muscle cause a tremendous

loss of tissue, as might be expected. Moresurprisingly, the type of muscle changesdramatically. These paralyzed subjectsexperience a sharp decrease of the rela-tive amount of the slow myosin isoform,whereas the amount of the fast myosinisoforms actually increases.

We have shown that many of thesesubjects have almost no slow myosin intheir vastus lateralis muscle, which ispart of the quadriceps in the thigh, afterfive to 10 years of paralysis; essentiallyall myosin in this muscle is of the fasttype. Recall that in the average healthyadult the distribution is about 50–50 forslow and fast fibers. We hypothesizedthat the neural input to the muscle, byelectrical activation, is necessary formaintaining the expression of the slowmyosin isoform. Thus, electrical stimu-lation or electrically induced exercise ofthese subjects’ muscles can, to some ex-tent, reintroduce the slow myosin in theparalyzed muscles.

Converting Muscle

Conversion of muscle fibers is notlimited to the extreme case of the

reconditioning of paralyzed muscle. Infact, when healthy muscles are loadedheavily and repeatedly, as in a weight-training program, the number of fast IIxfibers declines as they convert to fast IIafibers. In those fibers the nuclei stop ex-pressing the IIx gene and begin express-ing the IIa. If the vigorous exercise con-tinues for about a month or more, theIIx muscle fibers will completely trans-form to IIa fibers. At the same time, thefibers increase their production of pro-teins, becoming thicker.

In the early 1990s Geoffrey Goldspinkof the Royal Free Hospital in Londonsuggested that the fast IIx gene consti-tutes a kind of “default” setting. Thishypothesis has held up in various stud-ies over the years that have found thatsedentary people have higher amountsof myosin IIx in their muscles than dofit, active people. Moreover, comple-mentary studies have found a positivecorrelation between myosin IIa and mus-cle activity.

What happens when exercise stops?Do the additional IIa fibers then convertback to IIx? The answer is yes, but notin the precise manner that might be ex-pected. To study this issue, we took mus-cle samples (biopsies) from the vastuslateralis muscle of nine young, sedentaryDanish men. We then had the subjectsconduct heavy resistance training, aimed

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mainly at their quadriceps muscle, forthree months, ending with another mus-cle biopsy. Then the subjects abruptlystopped the resistance training and re-turned to their sedentary lifestyle, beforebeing biopsied for a third and final timeafter a three-month period of inactivity(corresponding to their behavior prior toentering the training).

As expected, the relative amount ofthe fast myosin IIx isoform in their vas-tus lateralis muscle was reduced from anaverage of 9 percent to about 2 percentin the resistance-training period. Wethen expected that the relative amountof the IIx isoform would simply returnto the pretraining level of 9 percent dur-ing the period of inactivity. Much to oursurprise, the relative amount of myosinIIx reached an average value of 18 per-cent three months into the detraining. Wedid not continue the biopsies after thethree-month period, but we strongly sus-pect that the myosin IIx did eventuallyreturn to its initial value of about 9 per-cent some months later.

We do not yet have a good explana-tion for this “overshoot” phenomenonof the expression of the fast myosin IIxisoform. Nevertheless, we can drawsome conclusions that can have usefulapplications. For instance, if sprinterswant to boost the relative amount of thefastest fibers in their muscles, the beststrategy would be to start by removingthose that they already have and thenslow down the training and wait for thefastest fibers to return twofold! Thus,

sprinters would be well advised to pro-vide in their schedule for a period of re-duced training, or “tapering,” leadingup to a major competition. In fact, manysprinters have settled on such a regimensimply through experience, without un-derstanding the underlying physiology.

Slow to Fast?

Conversion between the two fastfiber types, IIa and IIx, is a natural

consequence of training and detraining.But what about conversion between theslow and fast fibers, types I and II? Herethe results have been somewhat murki-er. Many experiments performed overthe past couple of decades found no evi-dence that slow fibers can be convertedto fast, and vice versa. But in the early1990s we did get an indication that arigorous exercise regimen could convertslow fibers to fast IIa fibers.

Our subjects were very elite sprinters,whom we studied during a three-monthperiod in which they combined heavyresistance training with short-intervalrunning (these are the foundation exer-cises in a sprinter’s yearly training cycle).At around the same time, Mona Es-börnsson and her co-workers at theKarolinska Institute in Stockholm re-ported similar findings in a study involv-ing a dozen subjects who were not eliteathletes. These results suggest that a pro-gram of vigorous weight training sup-plemented with other forms of anaero-bic exercise converts not only type IIx

fibers to IIa but also type I fibers to IIa. If a certain type of exertion can con-

vert some type I fibers to IIa, we mightnaturally wonder if some other kind canconvert IIa to I. It may be possible, butso far no lengthy human training studyhas unambiguously demonstrated sucha shift. True, star endurance athletessuch as long-distance runners and swim-mers, cyclists and cross-country skiersgenerally have remarkably high propor-tions—up to 95 percent, as mentionedearlier—of the slow type I fibers in theirmajor muscle groups, such as the legs.Yet at present we do not know whetherthese athletes were born with such ahigh percentage of type I fibers and grav-itated toward sports that take advantageof their unusual inborn trait or whetherthey very gradually increased the pro-portion of type I fibers in their musclesas they trained over a period of manymonths or years. We do know that if fasttype IIa fibers can be converted to type I,the time required for the conversion isquite long in comparison with the timefor the shift from IIx to IIa.

It may be that great marathon runnersare literally born different from otherpeople. Sprinters, too, might be congeni-tally unusual: in contrast with long-dis-tance runners, they of course would ben-efit from a relatively small percentage oftype I fibers. Still, a would-be sprinterwith too many type I fibers need not giveup. Researchers have found that hyper-trophy from resistance training enlargestype II fibers twice as much as it doestype I fibers. Thus, weight training canincrease the cross-sectional area of themuscle covered by fast fibers withoutchanging the relative ratio between thenumber of slow and fast fibers in themuscle. Moreover, it is the relative cross-sectional area of the fast and slow fibersthat determines the functional character-istics of the entire muscle. The more areacovered by fast fibers, the faster the over-all muscle will be. So a sprinter at leasthas the option of altering the characteris-tics of his or her leg muscles by exercis-ing them with weights to increase the rel-ative cross section of fast fibers.

In a study published in 1988 MichaelSjöström and his co-workers at the Uni-versity of Umea, Sweden, disclosed theirfinding that the average cross-sectionalareas of the three main fiber types werealmost identical in the vastus lateralismuscles of a group of marathon runners.In those subjects the cross-sectional areaof type I fibers averaged 4,800 squaremicrons; type IIa was 4,500; and type

52 Scientific American September 2000 Muscle, Genes and Athletic Performance

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UNEXPECTED EXPERIMENTAL RESULTS have practical applications for the ath-lete. The fast IIx myosin declined as expected during resistance training. But when trainingstopped, rather than simply returning to the pretraining level, the relative amount of IIxroughly doubled three months into detraining. So what does this mean for the sprinter,to whom IIx is crucial? Provide for a period of reduced training before a competition.

Copyright 2000 Scientific American, Inc.

IIx was 4,600. For a group of sprinters,on the other hand, the average fiber sizesvaried considerably: the type I fibers av-eraged 5,000 square microns; type IIa,7,300; and type IIx, 5,900. We have re-sults from a group of sprinters that arevery similar.

Although certain types of fiber con-version, such as IIa to I, appear to bedifficult to bring about through exer-cise, the time is fast approaching whenresearchers will be able to accomplishsuch conversions easily enough throughgenetic techniques. Even more intrigu-ing, scientists will be able to trigger theexpression of myosin genes that exist inthe genome but are not normally ex-pressed in human muscles. These genesare like archival blueprints for myosintypes that might have endowed ancientmammalian relatives of ours with veryfast muscle tissue that helped them es-cape predators, for example.

Such genetic manipulations, most like-ly in the form of vaccines that insert arti-ficial genes into the nuclei of muscle cells,

will almost certainly be the performance-enhancing drugs of the future. Through-out the recorded history of sports a per-sistent minority of athletes have abusedperformance-enhancing substances. Or-ganizations such as the InternationalOlympic Committee have for decadestried to suppress these drugs by testingathletes and censuring those found tohave cheated. But as soon as new drugsare invented, they are co-opted by dis-honest athletes, forcing officials to de-velop new tests. The result has been anexpensive race pitting the athletes andtheir “doctors” against the various ath-letic organizations and the scientists de-veloping new antidoping tests.

This contest is ongoing even now inSydney, but within the near future,when athletes can avail themselves ofgene therapy techniques, they will havetaken the game to a whole new level.The tiny snippets of genetic materialand the proteins that gene therapy willleave behind in the athletes’ muscle cellsmay be impossible to identify as foreign.

Gene therapy is now being researchedintensively in most developed countries—for a host of very good reasons. Insteadof treating deficiencies by injecting drugs,doctors will be able to prescribe genetictreatments that will induce the body’sown protein-making machinery to pro-duce the proteins needed to combat ill-ness. Such strategies became possible,at least in theory, in recent years as re-searchers succeeded in making artificialcopies of the human genes that could bemanipulated to produce large amountsof specific proteins. Such genes can beintroduced into the human body where,in many cases, they substitute for a de-fective gene.

Like ordinary genes, the artificialgene consists of DNA. It can be deliv-ered to the body in several ways. Sup-pose the gene encodes for one of themany signaling proteins or hormonesthat stimulate muscle growth. The di-rect approach would be to inject theDNA into the muscle. The musclefibers would then take up the DNA and

Muscle, Genes and Athletic Performance Scientific American September 2000 53

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SPRINTER AND MARATHONER reveal obvious differences inleg musculature. Fast fibers rely on anaerobic metabolism; slowfibers depend more on relatively efficient aerobic metabolism.

Thus, slow fibers are important in endurance sports, and fastfibers are key in events such as sprinting and weight lifting. Thesprinter is Brian Lewis; the marathoner, Khalid Khannouchi.

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add it to the normal pool of genes.This method is not very efficient yet, so

researchers often use viruses to carry thegene payload into a cell’s nuclei. A virusis essentially a collection of genes packedin a protein capsule that is able to bind toa cell and inject the genes. Scientists re-place the virus’s own genes with the arti-ficial gene, which the virus will then effi-ciently deliver to cells in the body.

Unfortunately, and in contrast to thedirect injection of DNA, the artificialgene payload will be delivered not onlyto the muscle fibers but also to manyother cells, such as those of the bloodand the liver. Undesirable side effectscould very well occur when the artificialgene is expressed in cell types other thanthe targeted ones. For example, if a genecausing extended muscle hypertrophy

were injected, this would lead to the de-sired growth of the skeletal muscles. Butit would probably also lead to hypertro-phy of another kind of muscle, namelythat of the heart, giving rise to all thewell-known complications of having anenlarged heart. So researchers have ex-plored another approach, which entailsremoving specific cell types from the pa-tient, adding the artificial gene in the lab-

54 Scientific American September 2000 Muscle, Genes and Athletic Performance

E veryone knows that when we age, our muscles weak-en and our movements become slower. But why isthat so?

With aging come a number of changes to the skeletalmuscles. Most marked is the loss of mass, which begins asearly as 25 years of age.By age 50 the skeletal muscle mass isoften reduced by 10 percent, and by age 80 approximately50 percent of the muscle mass is gone.

This age-related reduction is caused mainly by a loss ofmuscle fibers. By greatly thickening the individual fibers,weight lifting can stave off the loss of mass from the muscleas a whole, but it appears to have no major effect on the lossof fibers.

Before individual fibers are lost to atrophy, they changeshape and appearance.In young people,muscle fibers are dis-tinctively angular, whereas in the elderly they often appearmore rounded and in extreme cases banana-shaped.Further-more, aging seems to induce “type grouping”: in young andmiddle-aged skeletal muscle the fast and slow fibers are dis-tributed in a chessboard fashion,whereas in aged muscle thefibers cluster in groups of either slow or fast cells (this phe-

nomenon also appears in younger people suffering from cer-tain motor nerve–related diseases).

The findings have prompted some researchers to hypothe-size that fiber types cluster in elderly muscle as a consequenceof a complex process in which the muscle-controlling nervesswitch from one muscle fiber to another. Consider the motorunit,defined as all the muscle fibers controlled,or “innervated,”by a single motor nerve originating from the spinal cord. As we

age, some of these motor nerves “die.” The nerve’s musclefibers are then left without any input,so they,too,atrophy anddie—unless they are reinnervated by another motor nerve.

Intriguingly, if a muscle fiber is reinnervated by a nerve froma different motor unit type—for example, if a fast muscle fiberis reinnervated by a nerve from slow fibers—the fiber will beleft with conflicting signals. Developmentally it is a fast fiber,but it receives stimulation that leads to an activation patternthat fits a slow fiber.Ultimately, this change in stimulation ap-pears to transform the fast fiber to a slow fiber (or vice versa, inthe opposite case).

Aging appears to be harder on the fast fibers, which atro-phy at a higher rate than the slow ones do. So some re-searchers have long suspected that the distribution of fastand slow fibers gradually shifts as we age to favor the slowfibers.This, they reasoned, could help explain why a 10-year-old boy will outrun his 70-year-old grandfather in a 100-meterrace,whereas Grandpa might still defeat Junior in a 10K.

The hypothesis is somewhat controversial because it hasbeen difficult to prove that aging leads to an increase in

the relative amount of slow fibers. In a recent study, we setout to approach the problem a little differently.We persuad-ed a group of 12 elderly and frail subjects with an averageage of 88 years to submit to a muscle biopsy from their vas-tus lateralis muscle (which is located on the front side of thethigh and is one of the most well examined of human skele-tal muscles).Then, working with thin needles under a micro-scope, we dissected out single muscle fibers from the tissuesamples.We determined the myosin isoform composition ofeach of 2,300 single fibers.

We know that all humans have not only pure slow and fastfibers but also fibers that contain both the slow and the IIa(fast) myosin isoforms or both fast isoforms (IIa and IIx). In theyoung vastus lateralis muscle these hybrid fibers are scarce:fewer than 5 percent of the fibers contain both the slowmyosin I and fast myosin IIa isoform. In our elderly subjectswe found that a third of all the examined fibers containedthese two myosin isoforms. Astonishingly, this hybrid fiberwas the predominant type in the very aged muscle.

We concluded that the question of whether aging musclehas more slow fibers cannot be answered with a simple yesor no. What seems to happen is not a change in ratio be-tween slow and fast fibers but more an obfuscation of theborder between slow and fast fibers, so that in very elderlymuscle one third of the fibers are neither strictly slow nor fastbut rather somewhere in between. —J.L.A., P.S.and B.S.

MUSCLE AND THE ELDERLY

WEIGHT LIFTING can prevent some loss of muscle mass.But nothing can prevent changes in the shape and distribu-tion of different types of muscle fiber as we age (young mus-cle, top; elderly muscle, bottom).

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oratory and reintroducing the cells intothe body.

These techniques will be abused byathletes in the future. And sports officialswill be hard-pressed to detect the abuse,because the artificial genes will produceproteins that in many cases are identicalto the normal proteins. Furthermore,only one injection will be needed, mini-mizing the risk of disclosure. It is truethat officials will be able to detect theDNA of the artificial gene itself, but todo so they would have to know the se-quence of the artificial gene, and thetesters would have to obtain a sample ofthe tissue containing the DNA. Athletes,of course, will be quite reluctant to sur-render muscle samples before an impor-tant competition. Thus, a doping testbased on taking pieces of the athletes’muscle is not likely to become routine.For all intents and purposes, gene dop-ing will be undetectable.

Brave New World

What will athletics be like in an ageof genetic enhancements? Let us

reconsider our opening scenario, at themen’s 100-meter final. Only this time itis the year 2012. Prior to these Olymp-ics, it was hard to pick an obvious fa-vorite for the gold medal. After the pre-liminary heats, that is not so anymore.Already after the semifinals the book-makers closed the bets for the runner inlane four, John Doeson. He impressedeveryone by easing through his 1/8 finalin a time only 3⁄100 of a second from thenow eight-year-old world record. In thequarterfinal he broke the world recordby 15⁄100 of a second, but the 87,000spectators did not believe their eyeswhen in the semifinals he lowered theworld record to an unbelievable 8.94seconds, passing the finish line morethan 10 meters ahead of the second-place runner. This performance madeseveral television commentators main-

tain that the viewers had just seen “some-thing from out of this world.”

Not quite, but close. What could haveled to such an astonishing performance?By 2012 gene therapy will probably be awell-established and widely used med-ical technology. Let us say that 12months before the Olympics, a doctorapproached Doeson with a proposallikely to sorely tempt any sprinter. Whatif you could make your muscle cells ex-press the fastest myosin isoform? Undernormal conditions, this isoform is notexpressed in any of the major humanskeletal muscles, but the gene is thereand ready to work, like a dusty blueprintthat just needs a civil engineer and a con-struction crew to make it a reality.

This enticing myosin isoform wouldgive muscle fibers functional characteris-tics that correspond to those of the veryfast IIb isoform, found in the rat and inother small mammals that need bursts ofspeed to elude predators. This IIb iso-form has a much higher velocity of con-traction and so can generate more powerthan IIx or IIa fibers. Although Doesondidn’t really understand what the doctorwas talking about, he fully understoodthe words “velocity” and “power.”

The doctor enthusiastically went onexplaining his idea. The gene actuallyexpresses a kind of protein known as atranscription factor, which in turn acti-vates the gene for the very fast myosinIIb isoform. Such a transcription factorwas discovered a few years ago and wasnamed Velociphin. Holding a tiny glassvial in front of Doeson’s face, he in-toned: “This is the DNA for an artificialgene for Velociphin. Just a few injec-tions of this DNA into your quadriceps,hamstring and gluteus, and your musclefibers will start cranking out Velociphin,which will activate the myosin IIb gene.”

Within three months, he added, Doe-son’s muscles would contain a goodportion of IIb fibers, enabling him tobreak the 100-meter world record with

ease. Moreover, the doctor noted, Doe-son’s muscles would keep producing Ve-lociphin for years without further injec-tions. And without a muscle biopsyfrom the quadriceps, hamstring or glu-teus, there will be no way for officials todetect the genetic modification.

A year later, as he pulls on his tracksuit, Doeson recalls the doctor’s assur-ance that there would be no side effectsof the genetic treatment. So far, so good.After stretching and warming up, hetakes his place on the block in lane four.“On your mark. Get set. BANG!” Therunners are away.

A couple of seconds later Doeson isalready ahead by two meters. Over thenext few seconds, astonishingly, his leadgrows. In comparison with those of theother runners, his strides are visiblymore powerful and frequent. He feelsgood as he passes 30, 40 and 50 meters.But then, at 65 meters, far out in frontof the field, he feels a sudden twinge inhis hamstring. At 80 meters the twingeexplodes into overwhelming pain as hepulls his hamstring muscle. A tenth of asecond later Doeson’s patella tendongives in, because it is no match for themassive forces generated by his quadri-ceps muscle. The patella tendon pulls outpart of the tibia bone, which then snaps,and the entire quadriceps shoots upalong the femur bone. Doeson crumplesto the ground, his running career over.

That is not the scenario that generallysprings to mind in connection with thewords “genetically engineered superath-lete.” And some athletes will probablymanage to exploit engineered geneswhile avoiding catastrophe. But it is clearthat as genetic technologies begin trick-ling into the mainstream of medicine theywill change sports profoundly—and notfor the better. As a society, we will haveto ask ourselves whether new recordsand other athletic triumphs really are asimple continuation of the age-old questto show what our species can do.

Muscle, Genes and Athletic Performance Scientific American September 2000 55

The Authors

JESPER L. ANDERSEN, PETER SCHJERLING and BENGT SALTIN work to-gether at the Copenhagen Muscle Research Center, which is affiliated with the Uni-versity of Copenhagen and the city’s University Hospital. Andersen is a researcher inthe department of molecular muscle biology and a former coach of the sprint team ofthe Danish national track-and-field team. Schjerling, a geneticist in the same depart-ment, recently changed his area of specialty from yeast to a considerably more mus-cular creature, Homo sapiens. Saltin, director of the center, graduated from theKarolinska Institute in Stockholm in 1964 and worked as a professor of human phys-iology there and at the University of Copenhagen’s August Krogh Institute. A formercompetitive runner, he has also coached the Danish national orienteering team.

Further Information

The Cytoskeleton in Molecular Biology of theCell. Bruce Alberts et al. Third edition. GarlandPublishing, 1994.

Muscular Again. Glenn Zorpette in Scientif-ic American Presents: Your Bionic Future,Vol. 10, No. 3, pages 27–31, Fall 1999.

The Mystery of Muscle. Glenn Zorpette inScientific American Presents: Men—TheScientific Truth, Vol. 10, No. 2, pages 48–55,Summer 1999.

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Copyright 2000 Scientific American, Inc.