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    By Sara Brownell | September 4th 2009 01:21 AM | 6 comments | Print | E-mail | Track Comments

    Naked mole-rats are not your average rodent.  Hairless, insensitive to pain, and nearly blind with a social system more similar to termites than to other rodents- they never really seem to fit in! But, don’t be so quick to brush them aside as merely interesting trivia for those awkward moments at cocktail parties.  These wrinkly little beasts might unexpectedly hold the key to Ponce de Leon’s desired fountain of youth.

    As every hamster owner must learn to accept, the average small rodent lifespan is only about two years. Maybe three or four years, but that’s pushing it.  Guinea pigs can live up to five years; rabbits up to ten.  The oldest lab mice live about three years.  Naked mole-rats, however, despite being closely related and approximately the same size as mice, have been shown to live 29 years, over nine times longer!  What is even more intriguing is the female’s ability to have offspring up until about two years of her death.  This means that not only do naked mole-rats live longer, but they don’t age like other mammals.  Forget menopause, walkers, and Medicare bills- it appears as though naked mole-rats do not really age at all.  They are somehow immune to cancer, disease, and even normal age-related changes in metabolism and body composition.

    That’s really cool.  But not as cool as their body temperatures, which might actually be the secret to their long lifespans.

    Naked mole-rats are the only known poikiothermic (pronounced po-key-oh-thermic) mammals, which means that they are unable to internally regulate their body temperatures. Like other poikiotherms such as lizards and snakes, the temperature of the external environment determines the internal body temperature of the naked mole-rat. They have adopted behaviors that they can use to change their body temperature such as huddling with other naked mole-rats or changing positions in the burrow, but in general their body temperatures fluctuate with changing external temperatures. Even though these behaviors can keep a naked mole-rat much warmer than the temperature outside its burrow, on average, naked mole-rats have body temperatures about 3-5 degrees centrigrade lower than mice of a similar size. 

    So, what does lower body temperature have to do with longevity? 

    Quite possibly, a lot. 

    Researchers at The Scripps Research Institute in La Jolla, California have recently shown that body temperature has a significant effect on longevity. For all mammals besides poikiothermic naked mole-rats, body temperature is controlled by a small part of the brain called the hypothalamus. The hypothalamus is important for many regulatory functions of the body, including thirst, hunger, sex, growth, stress, and body temperature. As far as temperature regulation, there is thought to be a biological thermostat in the hypothalamus that sets a specific temperature that the rest of the body tries to maintain, much like a thermostat in a house. If the hypothalamus senses that the body is getting too hot, signals are sent out to cool down the body. You sweat. If the hypothalamus senses that the body is getting too cold, signals are sent out to heat up the body. You shiver. It is the Goldilocks phenomenon of not too hot and not too cold, all tightly controlled by a biological thermostat in a part of the brain that is no bigger than the size of an almond!

    While trying to prove the hypothesis that the hypothalamic thermostat does indeed control body temperature, Tamas Bartfai and colleagues at The Scripps Research Institute discovered an unexpected link between body temperature and average lifespan.

    Bartfai’s team engineered mice to have a higher local temperature near the thermostat in the brain. They took advantage of a natural protein called UCP2 that causes heat to be released in a localized part of the body, acting much like a space heater that warms up just one room in a house. They used UCP2 to generate heat specifically in the hypothalamus. They predicted that the hypothalamic thermostat would sense the extra heat, be fooled into thinking that the body was too warm, and then compensate by sending signals out to the rest of the body to decrease the core body temperature. And it worked. Mice with UCP2 had a higher local brain temperature in the hypothalamus and a lower body temperature. So, they validated what they initially set out to prove, but the really interesting part came into play when they started noticing that these mice lived longer.

    These cool mice had significantly longer lifespans: females had a 20% increase in average lifespan, which is equivalent to an extra 15-20 years in humans. Although the specific mechanisms underlying this increase have not yet been determined, scientists are investigating a link between lower body temperature and lower metabolism. Until this point, only calorie restriction has been consistently shown to increase lifespan in mammals. Since both calorie restriction and lower core body temperature result in decreased metabolic demand, it is possible that metabolic changes might explain the increase in lifespan in both of these situations. However, the really remarkable part of this story is that these mice had lower core body temperatures by approximately 0.5 degrees Celcius. Mice cooled by only half a degree centigrade had longevity increased by 20%!

    This brings us back to naked mole-rats, which have a body temperature of three to five degree Celcius less than mice of the same size. If half a degree increases a mouse’s life by 20%, could the naked mole-rat’s impressive lifespan be explained by its unusually low body temperature, which in turn leads to lower metabolic demand? Although this has not been directly proven, research on naked mole-rats has shown that they exhibit especially low basal metabolic rates for their size, suggesting that metabolic rate might be the link between body temperature and longevity. If so, then lower body temperatures might be the key to staying young; adjusting our internal thermostats might be a cool way to make 60 the new 30.

    References:

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    Buffenstein R. Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species. J Comp Physiol B. 2008 May;178(4):439-45. Epub 2008 Jan 8.

    Buffenstein R, Jarvis JU. The naked mole rat--a new record for the oldest living rodent. Sci Aging Knowledge Environ. 2002 May 29;2002(21):pe7.

    Conti B, Sanchez-Alavez M, Winsky-Sommerer R, Morale MC, Lucero J, Brownell S, Fabre V, Huitron-Resendiz S, Henriksen S, Zorrilla EP, de Lecea L, Bartfai T. Transgenic mice with a reduced core body temperature have an increased life span. Science. 2006. Nov 3; 314 (5800): 825-8.

    Comments

    Kimberly Crandell
    Sara,  Congrats on being the first entry into the contest!

    I have to admit, I had not even heard of a naked mole rat until a couple years ago when I watched an episode of "Kim Possible" with my daughter.  I had no idea they were so scientifically significant!

    The lower metabolism link is interesting.  I had heard the studies about longevity due to reduced calorie intake, but as this information show it seems like it may be more about the metabolism than the calories. A fascinating find - thanks for the article!
    Danna Staaf
    Sara! This is so incredibly cool! Awesomely researched and written.

    The only clinical cooling of humans that I remember seeing was related to heart attack patients--that immediate mild hypothermia increased survival or something like that. A quick google search found me an article about it.

    Seems like it could be the same mechanism--reduced metabolic demand?
    Fascinating article! This makes me wonder whether bats, which are also long-lived for mammals their size, have low body temperatures.
    I see that the Stanford I/O bio group is strong here. :-)

    Interesting article! Especially in light of the recent NY Times article on naked mole-rats not getting cancer!

    Hope you win!

    Very interesting. Good luck.

    Wow. I had no idea that naked mole rats were so useful to scientists in their research. I read through lots of the articles and I think yours is the best of the bunch. Good luck!