The fountain of youth revisited

Not too long ago, I wrote about my love of brownies and an article on caloric restriction. I wasn’t really planning on bringing up this topic again so soon but a recent Science paper on caloric restriction in monkeys is getting so much media attention that I just had to throw in my two cents.

In the article, a group of American researchers study control and calorie-restricted (30%) monkeys over 20 years. What they show is that the calorie-restricted monkeys have a reduced incidence of age-associated death, diabetes, cancer, cardiovascular disease and brain atrophy compared to the control monkeys. From the sounds of it, we can stop looking for the fountain of youth (it’s in Florida, by the way). The media absolutely loves this story, and news reports and videos are quick to claim that caloric restriction increases longevity in our closest cousins, and it must be good for us as well.

First, a disclaimer from the friendly folks at ScientificChick.com: In the recent years, solid, convincing and well-controlled studies have shown some benefits of caloric restriction in various types of experimental subjects ranging from yeasts to humans. I won’t go back into the pros and cons of caloric restriction in this post. There is good evidence out there that it can be beneficial in some instances, and also good evidence that it’s not for everyone.That being said, I believe there are many problems with this particular Science paper on caloric restriction.

In my opinion, a major issue with the findings is that the control monkeys (the ones not on caloric restriction) are fed ad libitum (meaning they can eat as much as they want). You might be able to guess the problem already, but let me give you an example just in case: I have a cat, and if I were to offer him a constant supply of what seems to me like gross, bland cat food, he would keep eating it until he would slip in a food coma. I think this goes for most species, including us (ever heard of the candy jar experiment?). Therefore, it’s very hard to judge if monkeys who eat as much as they want are eating the amount of food they should naturally be eating. Chances are they are eating more (breakfast, lunch and dinner are not served at regular hours in the wild). And this is particularly relevant because eating too much (or obesity) happens to be an important risk factor for all the diseases the study looks at (diabetes, cardiovascular problems, cancer, etc.).

Another issue with the article is that few of the findings show a statistically significant difference between the control and the calorie restricted groups, even though the researchers are studying a reasonably large number of monkeys. When your results are statistically significant, it means that what you are observing is unlikely to have occurred by chance. This concept is a hallmark of solid and convincing science findings and the media should be very careful not to hype findings that aren’t statistically significant. In addition, almost every single news article on this publication claimed that caloric restriction had an effect on longevity. While the study looks at age-associated diseases, the longevity (or life expectancy) parameter is not assessed at all (though the researchers do mention they plan on assessing this in the future).

Lastly, and perhaps most disturbing from my scientist point of view, the lead researcher in this study happens to be co-founder and member of the board of LifeGen Technologies, a company focusing on the impact of dietary interventions on the aging process. A little research on this company made it very clear to me that the more people buy this whole caloric restriction business, the more money the company makes. If that’s not a conflict of interest, I don’t know what is.

Now if you’ll excuse me, a new cupcake store just opened across from my building, and I must significantly increase the quality of my life by going over and eating a cupcake.

My cat, Mr Minou, is not a fan of caloric restriction.

Reference: Caloric restriction delays disease onset and mortality in rhesus monkeys. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R. Science. 2009 Jul 10;325(5937):201-4.

Who wants a memory booster?

One of my first posts was about erasing memories. That may be useful if you suffer from post-traumatic stress disorder or if you just sat through the last installment of the Transformers movies, however, I can think of more people who would benefit from memory enhancement rather than memory erasure. One recent publication in Science hints that this may be just around the corner.

First, how do we know what animals remember? One way to test memory in rats is by using object recognition. You present the rat with two identical objects and let the animal explore them for a few minutes. Then you replace one of the objects with a new object, and typically, the rat will spend more time exploring the new object than the old one (presumably because the rat remembers the old one). By testing rat visual memory performance using this simple paradigm, the researchers established that rats were able to retain information about an object for up to 45 minutes, but after 60 minutes the objects were forgotten and treated as new unknowns. The researchers then injected a special protein in a specific part of the rat’s visual cortex, a part of the brain that is important for processing visual information. Following the injection, the rats were tested again for object recognition, and low and behold, the rats were now able to remember object information for longer than 45 minutes. How much longer? 60 minutes? 100 minutes? 1000 minutes? Actually it was 14 months. The rats went from being able to remember an object for 45 minutes to being able to remember it for 14 months.

Now the relevance of this article mainly lies in the identification of the function of a part of the visual cortex. To confirm their findings, the researchers took control rats (that didn’t receive the special drug) and inactivated the brain cells in the section of interest of the visual cortex (ok, they destroyed them). Those rats couldn’t remember objects at all. Interestingly, the researchers also showed that if you inject the special drug, then introduce a new object, and then destroy the brain cells, the rats will still remember the object for a long time, meaning this specific region of the visual cortex is important for making new memories but not for storing those memories. These are all important findings that further our understanding of visual memory.

But 14 months?? Surely this kind of memory enhancement won’t go unnoticed. The researchers claim that “the role of the RGS-14 protein in the enhancement of visual memory makes this protein an important pharmaceutical target for the treatment of (...) memory defects as well as for boosting the memory capacity”. That being said, I don’t think this drug will hit the shelves anytime soon. First, in the article, the researchers have to inject it directly into a specific brain region, and I certainly wouldn’t volunteer for that. Second, the drug affects an important, ubiquitous protein with many functions, and it’ll be a while before we tease out all the potential pitfalls of toying with something like that.

Regardless, with the aging population and the ever-increasing need (or want?) for maximum brain performance, there is a huge market for memory enhancers and the race is on to develop the first one. Now is the time to ask and answer all the ethical questions that surround this issue. If you had access to memory enhancers, would you use them? What if they were really expensive? What if they had detrimental side effects? What if they had detrimental side effects and everyone in school or work used them to enhance their performance relative to people who don’t use them (Tour de France, anyone?)?

Memory enhancers: useful drugs or can of worms?

The object recognition task

Reference: Role of layer 6 of V2 visual cortex in object-recognition memory. Lopez-Aranda, M.F., Lopez-Tellez, J.F., Navarro-Lobato, I., Masmudi-Martin, M., Gutierrez, A., Khan, Z.U. Science 2009 325:87-89.