Edward Masoro began studying calorie restriction and life-span in 1975, when he was 51. Now 78, his appetite for gerontology is far from sated.
Physiologist Edward Masoro could be the only professor who's ever needed a helmet in the line of duty. At the University of Texas Health Science Center in San Antonio (UTHSCSA), where he worked for 23 years before retiring in 1996, he paced back and forth so vigorously while delivering his lectures that on one occasion, he walked off the lecturing platform and into a small trash can. Another time he collided with the classroom television mounted on the wall, but he continued talking, oblivious to the fact that he was bleeding from a gash on his head. A concerned student went up and tried to bandage the wound, but Masoro kept up his perambulatory teaching. "Everyone was on tenterhooks, worried that he would bang into the TV again," says Jeremiah Herlihy, a cardiovascular physiologist at UTHSCSA who often sat in on Masoro's classes.
Whether teaching, writing, doing research, or running a department, Masoro, a leader in the study of calorie restriction, tackles his work with single-minded intensity, colleagues say. Over 5 decades, the Oakland, California, native has penned approximately 300 scientific papers and review articles and nine books on topics that range from lipid metabolism and acid-base regulation in the body to evolutionary aspects of aging. His admirers call him a renaissance scientist: someone who is knowledgeable about virtually all aspects of physiology. "He's one of a dying breed," says physiologist Arlan Richardson, director of the Aging Research and Education Center at UTHSCSA, "one of the [few] people who has really thought about whole-animal systems."
At 78, Masoro, a short man with close-cropped brown hair and spectacles, now lives in Charleston, South Carolina, but he sustains an active voice in the field of gerontology. His latest book, Caloric Restriction: A Key to Understanding and Modulating Aging, is being published this month; he also co-edited the fifth edition of the Handbook of the Biology of Aging and is busily planning the next installment. Masoro has always forged along with extraordinary energy, according to retired physiologist Helen Bertrand, a former postdoc who joined the UT faculty in the mid-1970s. "In those days--no joke--he did the work of five people," she says. "Now that he's in his 70s, he can only do the work of three."
A Bumpy Beginning
Masoro's well-rounded expertise is the product of a career path that initially roved from one research area to another, sometimes unpredictably, before finally becoming immersed in the study of dietary restriction. Although you'd never guess it from his current C.V., his career got off to a rocky start. After receiving a degree in physiology from the University of California (UC), Berkeley, in 1947, he stayed to get a Ph.D. An undergraduate course taught by a dynamic endocrinologist, I. Lyon Chaikoff, had snagged his interest, and he joined Chaikoff's lab to study fatty acid biosynthesis. Although he learned a great deal from Chaikoff, Masoro says he found his mentor very difficult to work with. For instance, Chaikoff, a bachelor who lived at the UC Berkeley Faculty Club, typically plunged into his research activities at 7 a.m. and toiled until midnight; he expected his students to do the same, according to Masoro.
Still, Masoro's thesis project went well. "Everything I touched turned to gold," he says. "I've never had a period of research that was so free of disappointments." After 2 years, he had collected enough data to fulfill the requirements for his Ph.D., but Chaikoff didn't think he was ready to graduate and recommended that he learn additional techniques. Masoro ignored the advice. "I decided, to heck with that," he says, and submitted his dissertation in 1950. Chaikoff, infuriated, initially refused to read the document, says Masoro. However, because the other two advisers on Masoro's Ph.D. committee approved the thesis, Chaikoff signed off on it as well. But he made his displeasure clear. "I won't recommend you to be garbage collector," Masoro recalls Chaikoff telling him at the time.
So Masoro was in a bind as he started looking for his first job. But with help from James Olmsted, the head of the Berkeley physiology department, he landed an assistant professorship at Queen's University in Ontario, Canada. Masoro stayed at Queen's for only 2 years, however, partly because the university provided little support for research. In order to get a lab built--with funding from the agency that controlled alcohol sales in Ontario--he had to agree to study alcohol metabolism. But he also realized that Chaikoff had been right: He needed more experience. Because his grad school research had gone so easily, he says, he had little idea of the challenges involved in doing good science and had been "too immature" to understand that he required further seasoning: "Chaikoff was right to tell me I needed more training, and I was certainly wrong to end-run him. On the other hand, I think for him to punish me the way he did was also not very good."
Chaikoff, it turned out, was not the forgiving type, says Masoro. An enzymologist at the University of Wisconsin initially seemed interested in hiring Masoro as a postdoc, but he then said that he didn't have funding to support him. Masoro says he later heard through the grapevine that Chaikoff had put "a kiss of death" on his application. So Masoro instead arranged to go to Tufts University in Boston to train with biochemist Gerhard Schmidt, who apparently never consulted Chaikoff. Better yet, Tufts's physiology department urgently needed to fill a lecturer position, so it hired Masoro to teach as an assistant professor in addition to his postdoc stint in Schmidt's lab.
Soon after arriving at Tufts in 1952, Masoro found himself in another pickle. Although Schmidt was a charming and pleasant man at social get-togethers, "he was an absolute nut" in the lab, Masoro says: "If he didn't like what you were doing, he would throw books at you [and] crash glassware at your feet." Masoro says he eventually realized that Schmidt, who loved benchwork, wanted the lab entirely to himself at night and got upset if anyone intruded.
After a few months, Masoro decided to forgo the postdoc training and got permission from the department chair, David Rapport, to set up his own lab. But he had no grant money of his own. Fortuitously, Rapport had been talking with the U.S. Air Force about getting funding to study cold exposure, and at his suggestion, Masoro took over the new project.
From Science of Cold to Study of Old
Masoro settled in at Tufts and spent the next 10 years investigating how low temperature alters carbohydrate and fat metabolism in the liver. When Rapport retired, Masoro had hoped to take over as department head, but he wasn't selected for the position. Discontented, he left Tufts, and after 2 years at the University of Washington, Seattle, in 1964 he moved to Philadelphia to head the physiology department at the Woman's Medical College of Pennsylvania (now the Medical College of Pennsylvania). His scientific focus by then had shifted to exploring lipid and protein function in the internal membranes of skeletal muscle fibers.
In winter 1969, a University of Washington friend, gerontologist Ed Bierman, was organizing a workshop on metabolism and aging for the National Institute of Child Health and Human Development (NICHD), and he asked Masoro to attend. "I said, 'Ed, I don't know anything about aging,'" Masoro recalls. "He said, 'Almost nobody does. You know a lot about metabolism, so I want you there.'"
At the workshop, which was held in Vero Beach, Florida, Masoro found out that NICHD was soliciting grant proposals for research in gerontology. He and his Medical College colleagues applied for and won funding to study the effects of aging on skeletal and heart muscle function. Although Masoro now says that the experiments he contributed to the project were "very badly designed," the experience forced him to learn about gerontological science. "And the more I learned about aging, the more interested I got."
Mingling With the Mob
Masoro hooked up with four other scientists in Philly who also were doing research on aging: biochemist Richard Adelman of Temple University, biochemist Vincent Cristofalo of the Wistar Institute, invertebrate biologist George Baker of Drexel University, and pharmacologist Jay Roberts, a colleague at the Woman's Medical College. "We used to meet all the time. ... It was a very close-knit group." The members of the informal club, which became known as the Philadelphia mafia within the gerontology community, shared knowledge, ideas, encouragement--and frank criticism--of each other's work. Although the foursome later dispersed geographically, they remained good friends and went on to play influential leadership roles in the field of gerontology: Starting in the mid-'80s, Adelman, Cristofalo, and Masoro each were elected to serve as presidents of the Gerontological Society of America.
In 1973, Masoro moved to San Antonio to run UT's fledgling physiology department. That year, he attended another NICHD workshop on aging--this one in Seattle--where he heard a talk by Morris Ross, a veterinarian who studied rat pathology at the Fox Chase Cancer Center in Philadelphia. In work that confirmed earlier research by others, Ross presented compelling evidence showing that rats fed restricted diets not only lived longer than their fully nourished counterparts but also suffered from fewer diseases. "I was totally fascinated," Masoro says. "The thing that really struck me the most was [that] this was a very simple manipulation." He decided he wanted to move his research program in this direction.
Two years later, Masoro--then 51--received the first of many funding awards from the National Institute on Aging to study dietary restriction, and he spent the rest of his career answering some basic questions about the phenomenon. "He and Roy Walford did the pioneering work," says Richardson. "Ninety percent of the research back in the '70s and '80s in dietary restriction was coming from their two groups."
For instance, working with physiologists Bertrand, Byung Pal Yu, Roger McCarter, and other colleagues, Masoro found that dietary restriction's life-prolonging effects do not result from reducing body fat or metabolic rate (see Masoro Classic Paper  ), nor from cutting back on any specific dietary component. Instead, Masoro's findings revealed beyond a doubt that a decrease in calorie intake was the crucial factor. His team went on to discover that food-restricted animals have low plasma concentrations of insulin and an increased daily peak in glucocorticoid stress hormones. The latter finding led Masoro to propose in 1998 a new theory for how calorie restriction extends life: As a mild form of stress, it might prime animals to cope more effectively with intense stresses, such as exposure to heat or toxins--and as-yet-unspecified damaging agents that contribute to aging.
Whatever theory he is noodling upon, colleagues say, Masoro scrutinizes his findings with blunt and objective honesty. "Typically, a scientist falls in love with a hypothesis," says Bertrand. "Ed never has. If he gets a piece of data that says nah, nah, nah, your hypothesis won't work, ... he is unbelievably adept at modifying his hypothesis to fit the latest data." Applying this same critical eye more broadly, Masoro has gained a reputation over the decades for candidly dissecting weaknesses in colleagues' research at scientific meetings. "If he sees the flaw in your logic, he doesn't hesitate to point it out," says Richardson. But for Masoro, any such disagreements are purely scientific and never personal, Richardson adds.
In 1991, Masoro stepped down as chair of the physiology department to spend more time promoting gerontology, in part by founding the Aging Research and Education Center at UTHSCSA. When Masoro officially retired 5 years later, his colleagues threw him three farewell parties. By then, Masoro had been obliged to focus on a new aging process--his own. In 1994, overweight and suffering from serious blockages in his coronary arteries, he underwent heart bypass surgery. "Until I was 69, I paid no attention to my diet," he says. And although he doesn't advocate dietary restriction for the general public--he says he worries that people who attempt it might suffer from malnutrition--Masoro practices a mundane and sensible form of calorie restriction at his own table. He follows the standard low-fat, low-calorie diet that doctors recommend for cardiac patients and also goes for a brisk walk every day. ("I do a mile in about 15 minutes.")
Switching to a healthy diet wasn't that tough for Masoro, partly because he loves vegetables. As a teenager in California, he raised zucchini and tomatoes; in San Antonio, he grew all kinds of lettuce. And since moving to Charleston with his wife, Barbara, Masoro works in his garden when he isn't writing or editing. Still, the enjoyment he gets out of growing green things can't compare to his obsession with cultivating human knowledge through scientific inquiry. Looking back on his exploits, he sees an idyllic existence, despite the zigs and zags. In academic science, he says, "you ask a question, and you are totally in control of being able to try to answer it. ... How many walks of life give you that kind of freedom?"
* Ingfei Chen is a writer in Santa Cruz, California; she could use a helmet when she feels the need to thump her head against the computer.