(Inside Science) -- In March, the health media wrote of a new link between old age and caloric restriction. We were told that hunger is healthy; scientists praise intermittent fasting; and if you eat less you’ll live longer. In short, the message was clear: eating less increases lifespan.
The research that inspired these headlines used flies as study subjects, not people.
But the link between limited amounts of calories and living longer isn’t new. “I didn’t discover this, it’s a theory that’s been around since the 1930s,” said Margo Adler, the lead author of the study cited in the earlier coverage. Instead, in her paper published in BioEssays, Adler outlined a new argument as to why the well-fed appear to die young. Her hypothesis is based on data from animal studies she conducted at the University of New South Wales, using Australian neriid flies. However, the longevity-hunger link she observed doesn’t translate from the lab into the real world. So how often do lab-based experiments obscure the reality of the field? How does this affect the impact of their findings on human health?
Margo Adler and her colleagues produced a video about their research on calorie-restricted diets in neriid flies.
The prevailing evolutionary theory behind restricted diet and longer life states that when times are hard, animals reallocate their energy and resources into maintaining their bodies instead of expending valuable energy on sexual reproduction. “It makes no sense,” said Adler. “The idea that a fly would wait out a period of famine to reproduce is absurd.”
Adler argues that life extension from hunger in neriid flies is a lab artifact -- adding that the only thing likely to kill insects in the lab is old age. Predation, pathogens and temperature fluctuations would otherwise finish them off in the wild. It’s not about waiting until times are good to reinvest in breeding -- neriid flies and other short-lived animals don’t have that luxury anyway. Instead, it’s all about cellular biology.
“The ratio of protein to carbohydrates is the main driver, which acts on nutrient response pathways,” said Adler.
These pathways are shared between humans and other animals as small as flies.
When animals eat protein-rich diets, they essentially make hay while the sun shines, and concentrate on the production of new cells en masse with little attention given to quality control. In other words, the risk of cancer increases.
That the news stories focused on human health claims concerned James P. Gibbs, an applied ecologist at the State University of New York College of Environmental Science and Forestry in Syracuse, N.Y.
“I’m alarmed to see the [assertions] towards human health,” he said. “Rodent models are reasonable proxies for humans, but the physiologies in insects and humans are utterly different.”
Adler disagrees; pointing out that research shows eating too much protein can lead to cancer. It may be highly unlikely that short-lived animals in the wild such as neriid flies ever find themselves plagued by cancer — but longer-living animals do. This has led to suggestions that the effect may translate to humans, which some say has given credence regimes such as the 5:2 diet that recommends two calorie-restricted days per week. Nevertheless, Adler’s new hypothesis is built upon insect lab experiments, not human-derived data.
As Gibbs said, the jump from mammal experiments to assumptions about human health is significantly less cumbersome, due to the similarity of our physiological systems.
A new study published today in Nature Communications comes from 25 years' worth of data collected from rhesus monkeys. It too concluded that calorie restricted diets are linked to longevity. In fact, they found that monkeys who consumed calorie-rich diets were 290 percent more likely to suffer disease. They were also at a threefold increased risk of death. This contrasted with results from a similar study conducted by the NIH, which also used rhesus monkeys and found that calorie restriction had no effect on length of life.
In many cases, scientists use Drosophila (fruit flies) as their organism of choice for experiments. They breed rapidly. They’re easy to control. Perhaps most crucially, we know an awful lot about their DNA, possibly even more than our own. But Adler said this could be one of the factors that cause a discrepancy between results yielded in the lab and the outside world, “Most strains of fruit flies have been in the lab for thousands of generations, genetically manipulated to suit the needs of the experiment, so they’re not at all like the wild. That’s one of the benefits of using neriid flies — they’re not an artificial system.”
There’s a parallel to be made between the human health assumptions that are made with insect studies and the world of toxicology, said Gibbs. Pesticide regulations are implemented on the back of an immense amount of scientific studies, but they’re based on animals that are easy to maintain in the lab and not necessarily the wild animals that would be exposed to the chemicals.
“They’re excellent pieces of scientific work, but they fall apart in the real world,” he said.
“I’m not saying that science doesn’t mean anything in the field, but there can be a hybrid between field measurements and lab experiments,” he added.
Coincidentally, that’s exactly the direction Adler is taking with her next research project. She is attempting to mimic the wild while maintaining the scientific control needed to extract meaningful conclusions. Adler is going to place insects under a mesh in tanks of water out in the wild. The specimens will be exposed to predators, pathogens and temperature fluctuations, but Adler will still be able to control their food supply — the best of both worlds, she hopes, an approach that Gibbs said “is absolutely going in the right direction.”