Mariya V. PhD

Got it- to FAST? 😀
The past week has been a treat in terms of great talks on campus. At ASU we are super-lucky to have the Center for Evolution & Medicine, which holds weekly talks by amazing speakers.

When I saw that the upcoming seminar was related to diet and eating..or more specifically NOT eating or “dietary restriction”, I of course RSVPd in a heartbeat.

“Eat breakfast yourself, share dinner with a friend, give the supper to your enemy”- Russian Proverb

I’ve been in fact fascinated with caloric restriction for years now (I wrote a whole research paper on it in the first year of my master’s degree). You might have heard of intermittent fasting (e.g. popular in the CrossFit world), or the CR Society ( http://www.crsociety.org/ )- all are related to the concept that restricting food intake results in health benefits (from extending life to preventing and reversing disease).

I’m sure you can Google caloric restriction and find a bunch of information on its reported benefits..you would see this chart at the CR society website- the lifespan of calorie-restricted (CR) mice vs non-CR mice. You can see that those whose food intake was restricted by more & more % lived longer. Why do many animals (and perhaps humans) appear to be so well-adapted to eating less? The traditional interpretation of this CR phenomenon is that the dietary restriction effect “has evolved as a way to enhance survival & preserve reproduction during periods of naturally occurring food shortage”. In other words- being adapted to do well on restricted food intake during rough times would have helped our ancestors survive them & stay healthy to have kids later when the food situation improves.

The traditional interpretation of this CR phenomenon is that the dietary restriction effect “has evolved as a way to enhance survival & preserve reproduction during periods of naturally occurring food shortage”.

Experimental evidence with animals, however…supports a different hypothesis- the one Dr. Austad (Professor & Chair of the Department of Biology at the University of Alabama) presented to us last week. Again, I wouldn’t be able to cover everything he discussed during the seminar, but I do want to highlight a couple of main points!

I. First, even though the first book on dietary restriction (DR) dates back to the late 16th century, we still do not know the mechanism behind why DR seems to extend life and vigor in animals + delay disease such as cancers. METABOLISM was the original suspect, as metabolic rate goes down with fasting.. however, metabolic rate drops initially yet gradually goes back UP (takes 6-8 weeks to happen).. Since DR changes an unbelievable amount of physiological parameters (see screenshot ->) it is very hard to determine its mechanism.

II. Second, while many sources cite mice experiments showing life extension with caloric restriction.. those experiments are done with lab mice. When DR studies are done with wild mice, DR has no effect on longevity. WHAAAT!! I’ve never heard this before- in fact i was under the impression that CR/DR extends life in animals, period. Well, NO STUDY has ever found that DR extends life or improves health in nature (or even “nature-like” conditions). Mice in the wild actually do not have enough fat stores to reduce feeding except very briefly (wild mice has about 4% fat while a regular lab mice has 15%; also lab mice do not reproduce). In fact, mice in nature simply do not live long enough for the survival benefits of DR to be important. Another challenge to the original hypothesis that adaptation to dietary restriction enhances survival, is that DR increases mortality from some infections. Lastly, DR increases cold sensitivity (and cold is a major source of death in wild mice) and slows down wound healing.

Sounds like animals in the wild would not benefit from adaptation to dietary restriction… yet why is the positive DR effect observed in so many studies so common?

III. Well, even though wild mice do not live longer with restricted diets, DR still results in cancer protection for them. But even more importantly, DR has been found to protect against acute effects of many many toxins! Dr. Austad talks about this discovery in the following way:

 .. if animals can not afford to wait to reproduce..and they have to do it even when food conditions are poor, what they will do is broaden their diet. This means they might be ingesting a lot of toxins they are not normally exposed to (foods infected with fungi, new seed types that are well defended by the chemicals they wouldn’t normally encounter). So the hypothesis is that DR acutely induces broad defense mechanisms from a broad range of toxins

Toxicology studies have shown that mice that are calorically restricted survive a wide range of toxins. DR also acts as an acute (vs. chronic) protectant against other problems (see slide below). Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury and we can see that while ad libitum mice are dying steeply by day 7, those on DR of various proportions survive (30% DR is only 70% of normal food intake; ad libitum stands for eating as much as one wants). This is quite impressive!!!

These acute benefits of DR have very important implications. We can think about these effects actually protecting the body against the toxins it itself produces (like free radicals).. it also has clinically relevant advantages- e.g. patients on very strong drug cocktails fasting to avoid harsh side-effects. This suggests that the protective effects of DR could have clinical relevance unrelated to chronic benefits like life extension.

The new hypothesis explaining the evolutionary advantage of this paradoxical effect is that dietary restriction arose as a defense against novel exposure to toxins during food shortage.

So in conclusion.. we saw evidence suggesting that dietary restriction would NOT enhance survival in nature. Yet research has shown that DR increases health and life in a diversity of species. The new hypothesis explaining the evolutionary advantage of this paradoxical effect is that dietary restriction arose as a defense against novel exposure to toxins during food shortage.

My conclusion? I’m still excited about this topic- more than ever before!!! There is a lot of work done now on the timing of food intake as well (not just restricting the amount, but restricting the timing of eating and human health) and I can’t wait to post more about this (after I collect some necessary data though :).  Watch out for early May as I’ll be sharing some more info!