Monday, January 18, 2010

Giving Heat Shocks to Roundworms Extends Lifespan by Almost 40%


Would 6 heat shocks be the magic number for longevity? (Photo by pshutterbug)

Hormesis is an idea that has been getting a lot of attention recently in the anti-aging circles. The basic idea behind it is that a certain amount of stress may in fact be good for an organism.

There's a lot of scientific evidence in support of this idea, the most famous example being exercise. The view that all exercise is uniformly good for you is a common but naive view – we now know that it's the adaptation to the stress from exercise that brings the health benefits. The stress, which is bad in the short-term, causes the body to increase its own defense mechanisms, which is good in the long term.

So exercise is a useful and simple way to induce hormesis. Another common way to stress an organism is to give it heat shocks. Exposing lower organisms such as nematodes and fruit flies to heat stress generally makes them live longer.

The question, then, is what kind of heat shocks are the most useful ones for increasing lifespan? Just like exercise can be overdone and cause health problems (marathon runners are a common example), heat shocks can decrease lifespan in animals if they're used too much.

In a recent study by Wu et al., a varying number of heat shocks in varying temperatures was given to Caenorhabditis elegans to see how they affected lifespan (link). In this post, we'll take a look at the paper in more detail.

Young roundworm adults were divided into six groups, with each group given between 0 to 5 heat shocks during their lifespan. The heat shocks were given every 3 days, with heat exposure times being slightly shorter with each consecutive treatment. On the first day, all worms except those in the control group were heated at 35 °C for one hour. On the fourth day (groups 2-6), the treatment was 55 minutes at the same temperature, and so on. Two independent experiments were done:

In the first experiment, the mean lifespans of animals heatshocked, 1, 2, 3, 4, and 5 times are 19.0, 21.9, 23.7, 24.9, 25.8, and 26.4 days, respectively.

That is, with just one heat shock early in life, mean lifespan increased by 15.3%. With five heat shocks administered throughout life, mean lifespan extension was 38.9%. Here's the survival graph for the first experiment:


Hormesis: heat shocks and lifespan in roundworms
The second experiment gave similar results:

A single heat-shock on day 1 of adulthood significantly increased longevity (a 16.7% increase compared to controls). Multiple heat-shocks of 2, 3, 4, or 5 times extended mean life span 24.2%, 29.3%, 34.3%, or 38.4% as compared to controls.

As you can see from the graph and the data, the number of heat shocks is positively correlated with lifespan. Sounds good, right? A slight caveat:

Repeated exposure to mild heat-stress can significantly extend longevity; each single heatshock has a hormetic effect on life span, but the magnitude of the hormetic effect of additional single heat-shocks decreases as the animals age.

In other words, the older the nematodes get, the less they benefit from heat stress. It's worth noting that the duration of the heat shocks was also decreased with age – however, I assume the authors did this because longer durations would have been less than optimal in aged animals. Thus, just as the U-shaped curve of hormesis suggests, the benefits of heat stress are limited and that you can't simply heat-shock an organism into immortality.

The authors stress the distinction between initial mortality and the rate of increase in mortality, two aspects of the famous Gompertz mortality curve. Put simply, the curve expresses the exponential increase in biological aging after a certain point in time – which explains why more people make it from age 21 to 22 than from 77 to 78.

According to the authors, one heat shock early in life only decreases initial mortality without affecting the rate of increase in mortality, while multiple heat shocks affects both. On the other hand, they note that the Gompertz model does not fit perfectly with the lifespan of C. elegans (for example, the rate of increase in mortality seems to slow down with age). I'm not sure how useful this distinction is here anyway. Regardless of which factor is affected, the end result is that as the number of heat shocks increases, so does lifespan. Whether more than 5 heat shocks would've resulted in a longer or shorter lifespan is not known.

These results of course raise the question of whether heat stress might also extend lifespan in humans. Specifically, sauna as a potential anti-aging strategy comes to mind. I've only briefly looked into this, but so far I haven't found much evidence of a similar longevity effect in humans. Furthermore, the life expectancy in Finland – where saunas are very common – isn't exceptionally long compared to other Nordic countries. Still, a closer look is in order at some point.

For more information on lifespan and hormesis, see these posts:

My Current Health Regimen
Anti-Aging in the Media: New York Times on Caloric Restriction and Resveratrol
L-Carnitine, Exercise Performance & Oxidative Stress
Why Aging Is a Global Disaster That Needs to Be Solved



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3 kommenttia:

icantgoforthat January 19, 2010 at 3:22 AM  

Very interesting once again JLL!

There looks to be some indication that cold shocks also have some benefits, which once again is probably just Hormesis in action some way or another.

What are your thoughts on this, and the growing picture of the Hormetic response as an influential player in health? Another example that comes to mind is an article I read in New Scientist stating radiologists, and other people who are exposed to very low levels of radiation actually have cancer rates lower than the average population, a seemingly counter-intuitive response (well I guess not anymore it isnt).

Could it actually be possible my weekly indulgence in a gluten grain of some form (ok 90% of the time its pizza after a few beers) actually be providing a net-positive hormetic response!?

JLL January 19, 2010 at 11:06 AM  

@icantgoforthat,

I do think that we still have a lot to learn about hormesis. The radiation example is a good one, and the new study where cell phone radiation actually protected rodents from Alzheimer's may also have something to do with hormesis.

As for gluten and hormesis, I really don't know. It's an interesting idea though. Given that at least some of the health benefits of vegetables come from a hormetic reaction to "plant poisons" -- veggies don't like to be eaten, after all -- it might be possible. I wonder what Stephan @ wholehealthsource thinks about this idea?

Btw, I also allow myself a weekly indulgence in grains these days. So far pizza has been my standard choice.

- JLL

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