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Does Eating Less Extend Life?


Lifespan extension due to dietary restriction has been demonstrated in species ranging from yeast to flies to mice – and even primates too. Credit: Baweg/iStockphoto

By Margo Adler

Dietary restriction extends the lives of species as diverse as yeast, flies and mice, but is this effect simply due to artificial conditions in the laboratory?

Scientists have known for decades that one of the most reliable ways to extend lifespan in laboratory animals is to feed them less. Dietary restriction has been studied since the 1930s, and the lifespan extension effect it elicits has been demonstrated in species ranging from yeast to flies to mice. There’s even some evidence it occurs in primates too.

Research into the underlying mechanisms that drive the extended lifespan effect of dietary restriction is progressing rapidly, with great hopes pinned on the potential applications for human health. But an obvious question remains unanswered: why would eating less prolong life? More specifically, what is the evolutionary significance, if any, of this seemingly perplexing response that is shared so broadly among species?

One prominent evolutionary theory to explain the lifespan extension effect has prevailed in the dietary restriction literature for decades. The Adaptive Resource Reallocation Hypothesis takes into account the fact that dietary restriction not only extends lifespan but also reduces reproduction. The hypothesis suggests that in times of famine, animals have evolved to redirect their nutritional resources away from reproduction and into somatic (body) maintenance instead. This resource re-allocation is thought to help animals outlive the famine and hopefully reproduce later.

In a recent paper published in BioEssays, Dr Russell Bonduriansky and I have argued against the Adaptive Resource Re­allocation Hypothesis. We suggested instead that the lifespan extension effect is unlikely to have evolved in natural populations of animals, and is more likely to be the result of the artificial conditions of the laboratory.

Why might the lifespan extension response to dietary restriction be a laboratory artefact?

Abundant evidence suggests that dietary-restricted lab animals live longer than their “fully fed” counterparts because they have reduced rates of cancer and other old-age pathologies. But would most wild animals benefit from a reduction in late-life disease?

This seems unlikely, since mortality sources in the wild are very different from those in the lab. The great majority of species are small and short-lived, and most likely die young in the wild as a result of environmental hazards like predation or exposure to pathogens, parasites and extreme temperatures. Laboratory animals, on the other hand, are shielded from these challenges, and tend to die of old age and the diseases that accompany it. So if dietary restriction extends lifespan in the benign lab environment by reducing late-life pathologies, it might be unlikely to have any beneficial effect on survival in the wild, where most animals don’t make it to advanced ages.

What may be more important is that dietary restriction increases susceptibility to environmental challenges by reducing immune function, cold tolerance and the rate of wound healing. Dietary restriction might thus reduce, rather than prolong, survival in a wild environment, where such challenges pose a constant threat.

So if dietary restriction extends lifespan in the lab by reducing a mortality source (diseases of old age) that is rare in wild animals, and if it also appears to make animals more vulnerable to environmental hazards, then the effect may well be a laboratory artefact. If this is the case and wild animals are unlikely to live longer when food is scarce, then the extended lifespan response to dietary restriction cannot be an evolutionary adaptation.

To test this idea, we must examine effects of diet manipulation in more natural conditions – ideally in animals in the wild. Such research is difficult because manipulating diet in the wild would require constant tracking of wild animals and limiting or increasing their access to food. This sort of experiment poses a range of challenges for researchers, but some ongoing studies promise to bring us closer to understanding the effects of dietary restriction in natural environments.

Dietary restriction does not appear to trigger a resource reallocation

Another problem with the Adaptive Resource Reallocation Hypothesis, aside from the fact that it is unlikely to represent a real evolutionary adaptation, is that there is no evidence for a reallocation of resources from reproduction to somatic maintenance. There are a number of lines of evidence against this idea.

For example, scientists have tracked nutrient investment into reproductive and somatic tissues in flies, and found that fully fed flies invested more in both reproduction and somatic tissues than their diet-restricted counterparts. The diet-restricted flies still lived longer though, suggesting that an increased investment into the soma cannot explain lifespan extension.

Furthermore, the lifespan extension effect of dietary restriction can be elicited without actually manipulating nutrients. Nutrients act as signals to turn up or down important pathways in the body – pathways that are shared across eukaryotic species from yeast to humans. This shared architecture is important because it means that, although we are very different from animals like yeast and flies, we may have in common some ancient, evolved responses to food availability.

Scientists have figured out how to “trick” these nutrient-responsive pathways into turning up or down without actually manipulating food, by mimicking or blocking nutrient signals. What these studies have shown us is that lifespan can be extended by blocking pathway activation, even in fully fed animals, and it can be shortened by triggering the pathways, even in diet-restricted animals.

So it appears to be signals, rather than the allocation of nutritional resources, that drives the lifespan response to nutrient availability.

Why do responses to dietary restriction appear to be so similar across species?

So if resource reallocation can’t explain the extended lifespan response to dietary restriction, what is going on?

The key to understanding the effect is to look at the nutrient-responsive pathways mentioned above. These pathways result in numerous changes within the body, increasing cellular growth and reproduction rates when food is plentiful (full feeding), and increasing cellular recycling mechanisms when food is scarce (dietary restriction). These cellular recycling mechanisms include the well-studied processes of autophagy and apoptosis. Autophagy is a process whereby degraded or damaged portions of the cell are broken down and recycled back into the cell. Apoptosis, or programmed cell death, recycles whole cells systemically and is an important regulator of uncontrolled cell growth.

This increase in cellular recycling mechanisms may hold the key to the lifespan extension effect.

Why does cellular recycling increase during dietary restriction?

When food is scarce in the environment, animals are likely to increase cellular recycling mechanisms like autophagy and apoptosis in order to enable continued functioning with fewer incoming nutrients. These combined processes make the body less costly to run by reducing the size and number of cells, while they also allow the animal to recycle nutrients stored within its own body and cells, reducing the need for external nutrients and allowing the animal to survive on less.

This response is likely to entail a huge evolutionary advantage because, by lowering the baseline level of nutrients an animal needs for survival, short-term reproduction may be more attainable. For small, short-lived animals that are unlikely to survive long enough to see out a famine before commencing reproduction, this response could mean the difference between having some offspring and having none at all.

This evolutionary explanation is very different from the idea behind the Adaptive Resource Re-allocation Hypothesis, which suggests that short-term reproduction is sacrificed to promote survival.

Interestingly, increased cellular recycling triggered by dietary restriction appears to extend lifespan in a benign laboratory environment as a side-effect. The reason for this is that cellular recycling reduces degeneration in the cells, tissues and organs, and it also reduces rates of cancer. There is good evidence for this: researchers have blocked autophagy in both dietary-restricted and fully fed animals, and found that without autophagy, the dietary-restricted animals don’t live any longer than the fully fed animals.

Are there any implications for humans?

Although the extended lifespan response to dietary restriction may be simply a side-effect of an adaptation that may enable some reproduction in times of famine, the fact that we can elicit it in benign laboratory environments holds some promise for human health research. For example, if we can learn how to increase rates of cellular recycling, ideally without severely restricting food intake, perhaps this will lead to new clues to cancer prevention.

However, nearly all of this research has been conducted in laboratory animals, many of them very far removed from humans, and we are a long way from understanding the complex effects of nutrient availability, or interventions that mimic such effects, on human health and longevity. Moreover, any research into such effects must be careful to take into account the potential costs, which are likely to include reduced bone and muscle mass, reduced rates of reproduction, compromised immune function, and perhaps many other negative consequences of a low cellular growth rate.

We do not, after all, live in laboratories, so the costs that may be overlooked in many dietary restriction studies may apply not only to wild animals but to humans as well.

Margo Adler conducted this research at the Evolution & Ecology Research Centre, the University of NSW, and is now a postdoctoral research fellow in the University of Toronto’s Department of Ecology and Evolutionary Biology.