In search of the anti-aging gene

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In Search of the Anti-Aging Gene

By Peter DeMarco, the Globe

February 10, 2004

As a scientist searching for the fountain of youth, MIT biology professor Lenny Guarente always has been a bit of a maverick. When others laughed at anti-aging research in the early 1990s, he sensed a niche and dove in.

After making startling discoveries about how yeast cells age, he moved on to far more challenging mice and human DNA. An entrepreneur, he cofounded a biotechnology company in an attempt to produce the first anti-aging drugs.

But, as the son of blue-collar parents from Revere -- his father, Leonard Sr., was a clerk at General Electric in Lynn, and his mother, Norma, was a homemaker -- Guarente, who published his latest findings in January, was raised with enough common sense to hedge his bets. When not peering into a microscope, Guarente, 49, does all he can to stay young the old-fashioned way -- by hitting the gym regularly, eating a low-fat diet, and staying on top of the latest music. (Although his findings suggest extremely low-calorie diets can prolong life, he said he won't starve himself for unproven benefits.)

Biochemist Brian Kennedy said he's always been impressed by his friend's self-discipline. While other people chatted before intramural basketball games, Guarente was doing deep knee bends; when Kennedy and his wife brought a cake to Guarente's house to repay an invitation to dinner, "the first thing he did was look at the box and say, `Wow, 26 grams of unsaturated fat.' "

Guarente is as unabashed about his healthy habits and love for new music as he is passionate about his work. In 1995, he and his laboratory assistants discovered that a gene in yeast cells -- called SIR2 -- regulates the rate at which cells age. That led to an even more significant finding: Similar genes appear to exist in almost every living organism, including humans.

The goal now, Guarente said, is to find that aging regulation gene in humans, figure out its role and devise a way to trick it into slowing things down. By staving off the diseases of old age, Guarente said he believes it may be possible to extend the average life span by 30 or 40 "healthy" years.

"Aging is something that is extremely vivid," he said. "You can see it happening to yourself, to others. What's making it happen? And is there anything that can be done to regulate it? I found the scientific question really, really interesting and challenging.

"The personal angle was also there. Gee, if you can do this, you might actually be able to mitigate diseases of aging, and have a healthier life in old age and live longer."

Such fountain-of-youth fantasies don't relieve people of the need to take care of their bodies, he warned. While Guarente and other biologists have made important strides in figuring out the aging process in yeast cells and worms, it is likely to take decades to reach a similar understanding of human aging, if indeed such a feat is possible.

"I think if you're impatient in basic research, . . . you have no chance," he said. You've "just got to get in there and bang away at it."

Growing up on the slightly rough streets of Revere in the 1950s and '60s, Guarente saw his share of fistfights and tackle football. At Boston College High School , he climbed to the top of his class. As a student at MIT, he became entranced by biology, eventually assisting in ground-breaking work in gene transcription while a postdoctoral student at Harvard University .

And then there was the leap into the anti-aging field, part of mainstream science today, but considered half-crazy when Guarente entered the field a dozen years ago.

A sharp, forward thinker, Guarente's greatest strength is his willingness to listen to others, said Ed Cannon, president and chief executive officer of Elixir Pharmaceuticals, the biotechnology firm in Cambridge 's Kendall Square that Guarente helped create and still advises. "What's important isn't that his idea carries the day. What's important is that the best idea carries the day."

Guarente's other mark as a leader, said former assistant Heidi Tissenbaum, now an assistant professor at the University of Massachusetts Medical School in Worcester , is that he values his employees. Every summer and Christmas, Guarente has parties at his house for current and former lab workers. "That's really unheard of," she said. "I think that says a lot about what Lenny is about."

Sharing seems to come naturally to Guarente. His 2003 memoir, "Ageless Quest: One Scientist's Search for Genes That Prolong Youth," dedicated to his son, Jef, takes a personal look at his decade-long research, covering such topics as his divorce, his 15 minutes of fame on "Good Morning America," and his dreams for the future.

"As for me, I plan to glide through the rest of the 21st century the way I finished off the 20th," he wrote. "Lots of rock music, a good bottle of wine, the daily newspaper, and a ready book. It wouldn't be bad to settle down again, either -- maybe at age 100. . . . It will be fun to be around as long as possible."