Last week, scientists announced the interim results of one of modern physiology’s most closely watched experiments: the effects of caloric restriction on the lifespan of non-human primates.

The report was maddeningly mixed.

Caloric restriction seemed to reduce the incidence of several diseases, but when it came to mortality—a somewhat important factor when it comes  to longevity— the data were  statistically not significant. We still do not know if caloric restriction works in primates, which, of course, we are.

Is the culprit bad science? Cryptic binging at McBanana’s by the monkeys? Doubtful. Instead,  the answer may be summed up in one Disneyesque word: m-o-u-s-e.

In modern biological science today, no one mammal reigns quite as mightily as the mouse. By various counts we use anywhere from 30 to 100 million of them every year to research everything from cancer to diabetes to depression to bone disease and arthritis. Hundreds of millions in public money are used every year to breed, house, and feed and genetically manipulate mus musculus, often to useful and relevant scientific ends.

of mice and men and monkeys and longevity

Yet so powerful is today’s mouse lobby—the “mouse mafia”—that is has blinded much of the scientific establishment, and in particular the science and “health” media, to this 24-gram creature’s limits. Nowhere is this more evident than in the realm of research about aging.

For more than 80 years, biologists have been trying to tease out the mechanism behind one of nature’s greatest puzzles: why caloric restriction (CR)—adequate nutrition minus 40 percent of usual caloric intake—produces a 30-50 percent increase in lifespan in the mouse and rat, the only mammals, so far, in which caloric restriction works.

It is a tantalizing fact, mainly for its suggestion that cousin homo sapiens might someday reap its benefit. Thus has the caloric restriction effect  prompted no end of academic theories, lifestyle advice (one that frighteningly bans pizza, burritos and BBQ), and nutritional compounds. The most salaciously tracked recent breakthrough comes in the form of the much-vaunted “CR mimetics” such as resveratrol, the Harvard University-sponsored anti-aging compound recently sold to Glaxo Smith Kline for $750 million. A pill that can elongate life and health span--and with pizza.

The principal dogma behind caloric restriction and CR mimetics concerns the molecule known as IGF-1, short for insulin-like growth factor. IGF-1 is critical in humans—we would die without it—because it helps protect us from infection, inflammation, and heart disease, and because it keeps bones and muscles strong. But a counterintuitive mirror of this emerges in mice undergoing caloric restriction:  they live longer, and their IGF1 is reduced. Mice with low IGF1 are also healthy, with reductions in several age-related diseases.

But when it comes  to aging in humans, low IGF-1 is quietly turning out to be a bust. CR people, the few pizza-free masochists who can endure the regimen, show normal  IGF-1 levels, along with a slower rate of artery-aging , but is still too soon to judge its effects on lifespan. (Although a growing body of evidence suggests the gain may be as small as six pizza-free years.)

A much touted recent study of Ashkenazy centenarians showed another troubling fact—only a miniscule percentage of these remarkable people turned out to have impaired  IGF1. More: the much-vaunted resveratrol compounds seem to only work in fat-eating obese mice; normal mice given the red wine derivative experience no increased lifespan.

This week’s announcement about monkeys on caloric restriction for 20 years showed an important decrease in age-related muscle loss, which suggests that their IGF-1 may be a little closer to normal. Humans on caloric restriction diets have such boney derrieres that one of their chief complaints is discomfort in sitting, along with coldness, crankiness, and a lack of interest in Penelope Cruz.

So why the continuing scientific dogma? Cash is one factor. Enormous investments of public and private dollars require belief and constant justification.  Another reason is what might be called “gerontological correctness”—GC.  In establishment gerontology, reduced IGF-1 is seen as the perfect scientific foil to the fact-light anti-aging crowd’s advocacy of human growth hormone, the hormone that stimulates increased IGF-1.  (So rabid is gero-hatred for HGH that two key testimonies in baseball’s HGH hearings came from…gerontologists, who used mouse data to justify their opposition to its use.) Although there is good reason to be wary of HGH use—mainly for its affect on one’s wallet—moderately ratcheted-up IGF-1 is likely not one of them.  GC big mouths can’t stand the fact that the actress Susanne Somers might have something they don’t, besides nice legs.

There is one other reason, one that implicates us all: The understandable—and sometimes hypocritical—uneasiness we have about using monkeys for research. We want to live healthier, for longer, but we don’t want to feel bad about how we get there. Mice are easily abstracted. Monkeys…not so.  I understand that; someday we may decide that confining and experimenting on animals is indeed unnecessary and even a violation of mammalian dignity. But we are not there yet.

Is there a midway point? Perhaps. A  non-endangered,  short-lived primate might hold the critical key between longevity, IGF-1, and humans. There are several possibilities. One is the marmoset, a — okay, cute — Brazilian tree critter that only lives 7-9 years, about the length of one NIH grant (maybe its most important selling point). The marmoset’s key muscle groups age like ours; like average humans, it does not have compromised  IGF-1 levels. The cotton top tamarin is another candidate.

As sentient, rationale, information-retaining beings, we naturally  desire more—especially more life. If we really want it, science has to take off the blinders, and we’ve got to get a lot more tough-minded. As Bette Davis once remarked, “Growing old ain’t for sissies.”

Greg Critser is the author of the forthcoming Eternity Soup: Inside the Quest to End Aging (Harmony); his lab animal blog, Mouse Farm, is at, or subscribe with this button: Mouse Farm Greg Critser