Authors: Jörg Blech
Muscles and Metabolism
A
NUMBER OF YEARS AGO, 12 MEN GATHERED IN BOSTON BECAUSE they were fed up with having lost their physical strength. One of them was Arthur, a 62-year-old dockworker. During his whole career, Arthur was used to physical labor, until he was promoted to being a foreman at age 50. From then on, he usually had to carry responsibility rather than heavy weights. But some days, Arthur’s muscle strength was needed to help carry boxes full of scrap iron. To the amusement of his underlings, Arthur was too feeble to lift them. Manuel, another member of the flabby dozen, had a similar experience. At age 70 he was delighted to be a grandfather, but he was too weak to lift his three-year-old granddaughter.
Arthur, Manuel, and the other ten men volunteered to participate in a unique experiment designed by the physician Irwin Rosenberg and his colleagues at the renowned Human Nutrition Research Center on Aging at Tufts University in Boston. The researchers wanted to test a formula against the symptoms of aging. “We were not focusing on the cosmetic aspects of aging, those visible signs of decline—sagging skin, age spots, receding hairlines, more pronounced facial features, and the like—that cause people so much anguish and create a huge market for beauty products companies,” recounted Rosenberg, whom I met in his office at Tufts. Rather, he wanted to give back the men their lost vitality—an undertaking many considered impossible and dubious. Back then, many physicians, as well as a wide swath of the population, assumed withering away was a natural and inescapable part of getting old.
Irwin Rosenberg, however, was thinking outside the box. At one point it struck him that many older persons around him were leading strange lives. They didn’t have major illnesses like cancer or heart disease, and yet they weren’t living by themselves, instead depending on nursing assistance. These people were smart and in good shape mentally—but for some reason, their bodies were falling apart. Rosenberg had a hunch: In reality, these seniors had the full potential of being healthy. Their symptoms were not related to specific diseases but rather had been caused by the long period without physical activity and the resulting wasting away of muscle cells. These people were simply too weak to be healthy. In an effort to raise awareness of their plight, Rosenberg, as noted, proposed a new name: Sarcopenia, an overlooked phenomenon that, he suspected, should not be mistaken as a natural part of the aging process.
In order to prove his assumption, Rosenberg turned to the flabby dozen for help. To begin with, the 12 volunteers, aged 60 to 72, were thoroughly examined, then participated for three months in a training program three days a week. Arthur, Manuel, and the others were asked to do weight lifting at 80 percent of their maximum (defined as the heaviest weight a person can lift one time). Subsequently, they were examined again. Using lab tests, microscopic analysis, and magnetic resonance imaging, the doctors documented the changes after three months of training.
The results exceeded the expectations of physicians and participants alike. Arthur, the foreman, was able to triple his muscle strength. Initially, he could lift a weight of only 50 pounds, but now he could lift almost 150 pounds. Moreover, after the end of the study, he continued working out. As a consequence, his chronic back pain eventually disappeared. “From Arthur’s point of view, the best bonus of all was being able to keep up with the younger guys at the loading dock, much to their amazement and his amusement,” Rosenberg recounts.
1
Similarly, Manuel, the proud but weak grandfather, felt like a new man. Over the course of the study, the size of his leg muscles increased by 17 percent, and he lost more than 13 pounds of fat. The average result of the dozen participants was truly encouraging. Their muscle strength increased two to three times over, and their muscle mass grew by 10 to 15 percent.
NEVER TOO LATE
Shortly after this remarkable study, the young doctor Maria Fiatarone (now Maria Fiatarone Singh) joined the team at Tufts. She proposed a new study, the results of which became a milestone in sports medicine. Fiatarone went to the Hebrew Rehabilitation Center for the Aged, in Boston, and encouraged ten women and men aged 87 to 96 to train for eight weeks. Despite their advanced age, these courageous women and men were asked to train at 80 percent of their maximum capacity. The result of this test was greeted with awe: The mass of their thigh muscles grew by more than 10 percent, and their muscle strength almost tripled.
To Fiatarone, the most critical question was whether these changes actually improved the lives of her ten senior test subjects. Thus she asked them to walk a 20-foot course and found that the training indeed translated into increased quickness and sureness of step. These results also enhanced the mental mood of the elderly participants. “Every day I feel better, more optimistic,” said Sam Semansky, aged 93, who could get around again without a walker. “Pills won’t do for you what exercise does!”
2
Fiatarone continued her career and went on to hold the John Sutton Chair of Exercise and Sport Science at the University of Sydney. Irwin Rosenberg remained in Boston and watched his predictions proven right by many other studies. We actually can get back our vitality. True, no one can defy death. But we can systematically increase the number of healthy days in our lives. “We age biologically, not chronologically,” says Rosenberg. “If you maintain function, you can overcome the biological process.” Even individuals who have not jumped rope or have not run after a ball in years can have a second chance. Advanced age is “a dynamic state that, in most people, can be changed for the better no matter how many years they’ve lived or neglected their body in the past.”
3
ACTIVATING GENES
This chance for renewal is due to the amazing plasticity of our muscle system. There are more than 600 different muscles in the body, and the skeletal muscles (they execute our deliberate motions) comprise a huge organ that together account for about 50 percent of the body weight in a lean individual. Until recently, sports doctors were mainly interested in the heart, but now their attention is shifting toward these muscles and the larger study of the biology that makes us fit.
4
Muscle cells can be changed rather easily. They always respond to motion and strain: The size, strength, and contraction speed of single fibers depends on stimulation. Physical exercise affects the nucleus of a muscle cell and influences the production of certain genes and proteins. Molecular biologists are starting to study these processes and hope to gain insights allowing the development of better training methods.
Researchers have also discovered that our muscles play a key role in our health. Strengthening muscles changes their physiological composition, which, in turn, benefits other processes in the body. And now, scientists are finally beginning to understand the mechanics of muscle wasting. As we saw in chapter 2, after only a few days of rest, our muscles shrink. Contrary to popular belief, this atrophy is not a passive side effect of laziness but an active cellular process under the control of a specific set of genes. Inside the cell, some muscle proteins are chemically marked, allowing digestive enzymes to detect and chop them into amino acids, which are then used for other purposes. In the process, the fibers inside the cells are incrementally degraded, and the cells themselves get thinner and weaker—although they remain alive.
Apparently at least 90 different genes control such atrophy, the so-called atrogenes. The atrogenes are thought to be a legacy of our Stone Age past. Our odds of survival increase when we do not have to invest energy to maintain muscles that are simply idle.
Conversely, other genetic circuits control the buildup of new muscle structures. One part of the circuit was discovered when a remarkable boy was born in Berlin in 1999. He came into the world with a fully developed musculature, and by age four was allegedly so strong that he could hold a weight of more than six pounds with his extended arm. The pediatrician Markus Schülke, at Charité University Hospital in Berlin, discovered that this boy had a rare genetic mutation and lacked a protein, myostatin, that usually limits the growth of muscle cells. Additional tests revealed the boy’s mother had a very similar mutation and possessed only minute levels of myostatin. Small wonder she was a very successful sprinter in her younger years.
5
Under normal circumstances, the growth of certain muscles is triggered and controlled by bodily motions. In experiments, animals that are kept for four months in an environment where they can run every day on a treadmill will double the amount of small blood vessels in their muscles, as well as the number of mitochondria, the power plants of the cell. Obviously, muscle cells are able to sense physical demands and respond accordingly.
The physiologist Darrell Neufer, at John B. Pierce Laboratory in New Haven, Connecticut, has studied how this sensing system might work. In one test, he and his colleagues encouraged volunteers to repeat an exercise for 90 minutes on five consecutive days. They used only one leg to lift a weight that was 70 percent of their maximum capacity. On the fifth day, the researchers performed biopsies on both legs, removing tiny bits of muscle tissue from the trained and untrained limbs. The biopsies were carried out at different times: before training, immediately afterward, and many hours after. Finally, the researchers analyzed which kinds of genes had been activated in the muscle samples.
6
As expected, exercise had turned on a wide array of genes playing key roles in the metabolism. But surprisingly, this gene activity did not peak during or immediately after exercise. Rather, there was a time lag. Two to four hours after the workout, as the leg was recovering, the gene activity reached its maximum. It is this delayed response that allows the muscle to adapt to physical strain. Hours after exercise, new proteins are produced so that the muscle can grow. After a while, however, these proteins become degraded, which explains why repetition is so important. Only if the exercise is performed regularly will the level of proteins remain high. This cumulative effect finally makes us fit.
The composition of muscle cells is equally important because skeletal muscle cells can be subdivided into distinct types. At one end of the spectrum is type-II-b. These are known as fast-twitch glycolytic muscles. They can act quickly because they burn up glycogen. They are quite strong but quickly get fatigued. They contain only a few mitochondria (about 1 percent of the cellular volume).
At the other end of the spectrum is type-I. These slow-twitch oxidative muscles chiefly oxidize fatty acids as fuel. They are not terribly strong but have endurance and contain many mitochondria (3 to 10 percent of the cellular volume). In addition, there are more subtypes such as fast-twitch oxidative, also containing abundant mitochondria.
While the classification of all these subtypes might appear confusing, they have a profound influence on our health. The more oxidative muscles we have, the better. Most persons actually have a mosaic of the different subtypes. The pattern is first set over the course of the embryonic development and can greatly vary among individuals. The proportion of desirable type-I muscles ranges from 13 to 96 percent and averages 50 to 60 percent. Individuals bearing many type-I muscles are often good endurance runners.
7
TRANSFORMING THE BODY
Until recently it was assumed that we cannot control our muscle-type patterns. But the physiologists Jan Carlsson and Bengt Saltin started to study the molecular details and soon abandoned the old tenet. In animal experiments, for example, it has been shown that individuals can alter whole muscles, from one type to the other, and back again. The physician R. Sanders Williams, at Duke University Medical Center in Durham, North Carolina, says, “Whatever the genetic predisposition is—the effect of physical activity is predominant.”
8
Each healthy human, fat or lean, is able to change the composition of his or her muscles by using them. If muscle cells are idle most of the time and are only occasionally used for heavy tasks, they morph into type-II-b and are not particularly good for our well-being.
However, jogging and bicycle riding stimulate muscle cells and turn them into the much-preferred oxidative muscles with their widespread benefits. Beyond bestowing endurance and stamina on our bodies, they will benefit the body’s metabolism.
We can exploit this throughout life because our astonishing muscular plasticity remains intact even in old age. As Williams states: “You don’t need stem cells to be fit.” Rather, you can use regular exercise to outfit and supply your body systematically with healthful oxidative muscles.
Exercise not only changes the composition of the muscular system but also a whole range of measurements throughout the body. Irwin Rosenberg has come up with ten distinct measurements he calls “biomarkers.”
9
By following these biomarkers during a training period, one can show that exercise invariably helps the body. The growth of the muscle mass and the increase of strength, two of the biomarkers, are effects one would expect above all. But Rosenberg and his colleagues at Tufts University have identified others as well.
Basal Metabolic Rate
The term metabolism refers to the many biochemical processes occurring constantly in our body. The basal metabolic rate describes the total sum of these processes while the body is resting, whether in the morning, when we sleepily open our eyes, or at night, when we nod off. Over the course of time our basal metabolic rate incrementally decreases. Thus a 25-year-old woman sleeping burns more calories than her 80-year-old grandmother, who weighs the same and is also having a siesta.