Aging is optional! Take two of these pills and call me in the morning.

We’re getting older.

Not exactly a surprise, I know, but I didn’t mean you and me are getting older. I meant we are getting older, as a population. In 2001, one Canadian in eight was aged 65 or older. By 2026, one in five will be 65 or older. So what should we do with an increasingly aged population? Well, this being a North American consumer culture, the sensible thing to do is try to sell them stuff. I mean, think of the size of the market!

Right now, a significant amount of research is being devoted to aging. The main focus is to try to slow down aging (partly by developing marketable supplements and such). As some of you might know, even my own PhD thesis project is on how to slow aging in the brain. Loyal readers of ScientificChick.com will also be aware of recent articles about caloric restriction, a potential way to keep old age at bay. Thankfully, a recent publication in Nature suggests a much easier way to live longer: forget starvation, all you have to do is pop a(nother) pill!

In this article, American researchers show that mice that eat rapamycin supplements starting at 600 days of age (senior citizens in mouse years) live longer, up to 14% longer for females and 9% longer for males. What’s more, rapamycin supplementation did not change the causes of death. The researchers propose that this drug could be acting by postponing death from cancer, by delaying mechanisms of aging, or both.

How does rapamycin work? Well, as you might expect with a miracle drug like this, we’re not really sure. Rapamycin is an inhibitor of a pathway called mTOR. The mTOR pathway has many functions in your cells, like coordinating the survival response arising when there are changes in nutrient and energy availability, and dealing with potentially deadly stresses, such as oxidative stress (the kind of stress fancy juices packed with antioxidants are supposed to battle). Since the mTOR pathway acts kind of like a central sensor of cell health, it makes sense that it would be implicated in regulating lifespan. Exactly how rapamycin is working its magic, though, is probably what the researchers are trying to figure out for their next article.

Could the increase in longevity following rapamycin supplementation be related to the effects seen with caloric restriction (the “eat less, live longer” paradigm)? Well, mice on rapamycin show no change in body weight, so we know the drug is not acting through a caloric restriction mechanism. The converse, however, may be true: it is thought that the beneficial effects of diet restriction may also be due to an inhibition of the mTOR pathway.

So don’t throw out the double-stuffed Oreos just yet, but don’t eat half the box either: rapamycin pills for humans won’t be on the shelves tomorrow. While mTOR inhibitors are currently being used to treat a few conditions (transplant rejection and some cancers, for example), there’s still a lot of work to do to tease out all the potential interactions and side effects.

Longevity in pill form? To me, it would feel like cheating the system. And if there’s one thing we keep learning over and over in the life sciences, it’s that trying to cheat Mother Nature always has some unintended consequences.

A great illustration of the aging mouse by TS Rogers

Reference: Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. Nature 2009 16;460(7253):392-5.

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.

The secret to eternal youth? Say goodbye to brownies.

You’ve heard of Atkins. You’re familiar with Weight Watchers. You probably know about the South Beach Diet. Well, there’s a new diet in town, and it’s called the “Longevity Diet”. It’s inspired by a relatively new hot topic in the life sciences called caloric restriction. As the name implies, it essentially means eating less, and it's hailed not so much as a weight loss strategy as an anti-aging solution. While I’m usually excited about new simple ways of changing daily habits to live a healthy life, this one I’m not sold on yet. You may remember that I like cheese. You may also remember that I like brownies. So obviously, I’m not too excited to hear that eating less is extra healthy. Especially since most caloric restrictions studies suggest you have to cut back anywhere from 30% to 60% of what you eat to see an effect.

So far, most of the really convincing data on caloric restriction slowing down the aging process have been carried out in model organisms that fit in your pocket: rats, mice, worms, all the way down to the tiny yeast. I personally would be reluctant to extrapolate those findings to humans. Surely worms don’t have the same kind of relationship with brownies that I do. However, one recent study looks at caloric restriction in healthy humans, and it’s hard not to take notice.

Researchers from Germany took 50 normal-to-overweight elderly subjects (sorry, Mom, in this case, “elderly” means 60ish, but the important thing is to be young at heart!) and divided them into groups. One group was told to not change their eating habits, and one group was put on 30% caloric restriction for 3 months. Before the study and after the 3 months, everyone’s memory was tested using simple tests like remembering a list of words. Well, I’m very sorry to say, but after 3 months, the group who ate less did significantly better at the memory tests. Sad but true.

During the study, the volunteers were monitored for many different biological indicators (such as cholesterol, insulin, inflammation, and cellular stress), in hopes of identifying the mechanisms responsible for the effects of caloric restriction. The one mechanism that really stood out and that showed a solid correlation with the memory improvements is insulin: the group on caloric restriction had lower insulin levels. Insulin is a hormone responsible for taking the sugar out of your blood and storing it in your liver and muscles to use when energy is needed, but it also plays an important role in keeping your brain healthy. When you have less insulin circulating in your body, you become more sensitive to it, and this sharpens and improves how your body (including your brain!) reacts to insulin. This may be why the group who ate less performed better on the memory tests.

So, throw out the cheesecake? I’m going to wait a little before I draw any solid conclusions, as there is still a very ongoing debate over caloric restriction. One side is claiming significant benefits like longevity, healthy aging and protection against age-associated diseases (think Alzheimer’s). The other side is critical of the methods and models used, as well as the contradictory results, and points to the downsides of caloric restriction, especially during the reproductive years. Not eating enough can also lead to the breakdown of muscles (and remember, your heart is a muscle), which is very important to consider if you have an active lifestyle. Interestingly, in this study, the authors show that the caloric restriction group lost a significant amount of weight, but did not lose body fat. Healthy? I think the jury is still out, but hopefully more well-controlled human studies will shed some light on this potentially exciting and easy way to fend off the effects of the ticking clock.

Learn to make these, shorten your healthy life expectancy?

Reference: Caloric restriction improves memory in elderly humans. Witte AV, Fobker M, Gellner R, Knecht S, Flöel A. Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1255-60.