Valter Longo is one of the more recognizable names in calorie restriction research. Beyond the science, his most noteworthy recent achievement has been to figure out how to commercialize the research, pulling in for-profit funding by packaging low-calorie diets as a medical product. This has helped to fund a series of advances in quantifying the effects of reduced calorie intake and fasting in humans, in search of the 80/20 point for optimal benefits, and along the way generating new knowledge of the effects on the immune system and other important areas of cellular metabolism. One of the most interesting outcomes is the accumulation of evidence to suggest that low-calorie diets can be about as effective as fasting in our species, at least in the near term.
As an aside, the tale of Longo's early work on the biochemistry of aging, provided in the article here, is illustrative of the degree to which the field was held back, both internally and by the rest of the research community. Aging research was a backwater, disrespected, lacking in funding. We could be ten to twenty years further ahead in treating aging as a medical condition than we are today, had the study of aging been taken as seriously as was the study of age-related diseases over the past fifty years. It is just one more example of the irrationality of the human condition that people are so enthused about research to treat heart disease, Alzheimer's disease, and so on, but reject outright work on the root causes of these conditions. The only way to cure age-related disease is to control the processes of aging - everything else is just putting thin patch over the problem and hoping. We should be thankful that this era of deliberate repression of aging research has largely come to an end, thanks to persistent and outspoken advocacy by those within and without the research community, and the field now has a chance to grow in funding and support.
He knows he sounds like a snake-oil salesman. It's not every day, after all, that a tenured professor at a prestigious university starts peddling a mail-order diet to melt away belly fat, rejuvenate worn-out cells, prevent diseases ranging from diabetes to cancer - and, for good measure, turn back the clock on aging. But biochemist Valter Longo is convinced that science is on his side. He now believes he's developed a diet that may boost longevity - by mimicking the effect of periodic fasting. His approach stands out because he insists he can use certain combinations of nutrients to trick the body into thinking it's fasting without actually being on a punishing, water-only diet.
Intrigued, we reviewed dozens of scientific studies and talked to a half-dozen aging and nutrition experts about fasting in general and Longo's diet in particular. Our conclusion? Fasting does appear to boost health - certainly in mice, and preliminary evidence suggests it might do so in humans as well, at least in the short term. It's not yet clear whether that's because abstaining from food prompts cellular changes that promote longevity, as some scientists believe - or because it simply puts a brake on the abundant and ceaseless stream of calories we consume to the detriment of our health. Either way, it can be a powerful force.
Mice and rats on fasting regimes are slimmer, live longer, and stay smarter and physically stronger as they age. They resist tumors, inflammatory diseases, and the neurodegeneration that characterizes diseases like Parkinson's and Alzheimer's. They handily fight off infection and can even sprout new neurons. They don't end up with diabetes, autoimmune disease, high cholesterol or fatty livers. Longo believes he knows why. Fasting, he and others argue, gives cells a break to rest, renew, rebuild themselves and, essentially, take out the trash as the body shifts from storing fat to burning it. They can't do that when the body is constantly ingesting food, stockpiling excess calories and pushing cells and organs to exhaustion.
Of course, many exciting findings that hold true for lab mice don't translate to more complex human biology. Small, short-term studies in humans do show that periodic fasting reduces weight, abdominal fat, cholesterol, and blood glucose, as well as proteins like C-reactive protein and IGF-1 that are linked to inflammatory diseases and cancer. But it's not clear how long these effects last or whether they translate into any lasting clinical advantage - such as fewer heart attacks or longer lifespan.
In the 1990s Longo was growing frustrated with attempts to study longevity in humans, and even mice, without having adequate tools to drill down into the genetic mechanisms underlying aging. He transferred to a genetics lab focused on yeast, figuring that would let him study the mechanisms of aging in the simplest of organisms. Few people took his early results seriously. Studying aging was still considered flaky. And many scientists at the time were deeply skeptical that you could learn much about human biology by studying simple yeast. "If someone said, 'What are you working on?' we would say oxidative chemistry. You couldn't say aging. That was viewed as a joke." Convinced his work was important, Longo kept his head down and kept going.
In just a year, Longo was able to work out a genetic pathway to describe aging in yeast and show that food - proteins and sugars - could speed aging. It was 1994. "I was so excited, I thought people were going to say, 'This is the discovery of the century.' Of course, it was sent back - rejected." He rewrote the paper and resubmitted. No luck. He couldn't get any of the work published without taking out every last reference to aging. As years passed, other groups started publishing work detailing, as Longo had, specific aging pathways, first in worms and eventually in flies. "The frustrating thing is that we had all of these things figured out and no one was listening."