Cool Mice Live Longer (humans too?)
 

Cool Mice Live Longer



http://www.the-scientist.com/news/home/27374/

Genetically reducing the core body temperature of mice by a half-degree Celsius helped them live 15 percent longer, a finding that could shed light on how calorie restriction helps prolong life, researchers report in Science.

"Calorie restriction was already known to be associated with reduction of core body temperature in rodents and in primates," co-author Bruno Conti, from the Scripps Research Institute in La Jolla, California, told The Scientist. "What was not known was if the reduction was simply a consequence of calorie restriction or if it also contributed to its beneficial effects. Our studies demonstrate that the latter may be true."

Past research showed lowering core body temperature slowed aging and prolonged life in poikilotherms such as fish. Whether this was also true for homeotherms had not been demonstrated.

Conti and his colleagues engineered mice that had an overheated hypothalamus. The preoptic area of the hypothalamus serves as the central thermostat for the brain, so heating it up turns down the core body temperature. Specifically, the researchers focused on the hypocretin gene. Hypocretins are appetite-promoting neuropeptides expressed in just 3,000 or so neurons in the lateral hypothalamus, near the preoptic area. The researchers generated transgenic mice using plasmids linking the hypocretin gene to uncoupling protein 2 (UCP2).

UCP2 is found in the inner mitochondrial membrane and uncouples electron transport from ATP production, dissipating the proton gradient energy as heat. Over-expressing UCP2 therefore elevated the hypothalamus temperature in the mice. The result was that core body temperatures were lowered by 0.3 degrees to 0.5 degrees C.

Experimental female mice lived an average of 20 percent longer than controls, while experimental males had a 12 percent greater life expectancy. Douglas Osei-Hyiaman at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, who did not participate in the study, noted in an email to The Scientist that the greater increase in life expectancy in the female mice might suggest that "sex hormones may help some mice attain a lower core temperature faster than others."

"What I find interesting about [the study] is that you can isolate one of the seemingly small aspects of the many physiological effects of caloric restriction and still get an effect on lifespan, although not as much as with real caloric restriction. This suggests each of the effects caloric restriction has may contribute incrementally," said Leonard Guarente, of the Massachusetts Institute of Technology in Cambridge, who did not participate in the study.

Future longevity studies or research into mutations that increase lifespan "should also see whether or not there's a reduction in the core body temperature, which should be easy to do," Matt Kaeberlein, from the University of Washington in Seattle, told The Scientist.

"The question now is what mechanisms are responsible here?" said Kaeberlein, who was not involved in the study. "You should see if all the other biomarkers that correlate with increased lifespan change. Is there reduced oxidative damage, for instance? You should also see if these mice have reduced pathologies of aging, or if these mice, when bred with others that reflect disease models such as Huntington's or Alzheimer's, have offspring with a reduced onset of pathology."

The experimental mice indirectly appeared to have increased metabolic efficiency, Conti said. When starved for about a day, they lost significantly less weight than controls, and while the transgenics consumed the same amount of food and water as controls, experimental males weighed 10 percent more, suggesting they required fewer calories to live, most likely reflecting the reduced energy required to maintain a lower core body temperature, he suggested.

Conti noted that the research team next plans to determine whether the effects of lowered core temperature are additive to the effects of calorie restriction by placing the transgenic mice on calorie-restricted diets.

"You can try these mice out on exercise regimens, or [try] giving them high-fat diets and seeing what effects those have on their longevity," USDA scientist James Joseph at Tufts University in Boston, who did not participate in the study, told The Scientist.

Another avenue of research could be to see if mitochondrial function throughout the bodies of the experimental mice matches up "with the same changes observed in calorie restriction, Pere Puigserver at Johns Hopkins University in Baltimore, who was not a coauthor, told The Scientist via email.

Glad to see my temperature at 35.2 degrees celsius (95.36 degrees Fahrenheit) this morning :) My father has the same temperature readings as me too, and he doesn't even do CR lol... he also looks far younger than his age =/

It seems that lower temperature in humans will mean longer life in humans also! see the following link...

On average, people who have a lower body temperature live longer, as do those with lower levels of insulin, and those with higher levels of DHEAS.
http://news.bbc.co.uk/1/hi/health/2167316.stm

Don't tell my wife. Her feet are already too cold as it is.

Wouldn't people living in cooler climates show an effect if this were the case? Even being homeothermic, I'd guess that there would have to be some effect.

Interesting question.

Is the lower body temperature what causes the effect? Or is it that with a lower body temperature you need to burn less fuel, and thereby generate fewer free radicals and place less stress on cellular machinery simply to maintain body temperature?

Of maybe its just because meat lasts longer if you keep it cold.

When mammals such as bears, and even moreso various fish, reptiles, and insects hibernate, their metabolism slows way down and in the case of mammals, I believe, their body temperature drops significantly, so wouldn't slower metabolism slow their aging too? (The flip side is, to the extent that one would, wouldn't one turn into a zombie so to speak- post-halloween pun not intended)- I mean, be lethargic? Anyway, personally I love feeling warm after a great workout, not cold with hunger.

I just turn up the heating a bit =/ works great!

I don't feel tired or anything from having a low temperature, in fact I prefer it cold and sometimes get a bit uncomfortable with my peak temperature during the evening.

LOL ~ the picture... the first thing I thought of when I saw your title was a little mouse with sunglasses and a leather jacket :lol:

Chemical reactions take place faster at higher temperatures. The temperature dependence is defined by the the Arrhenius Equation. Things wear-out faster at higher temperatures.

On the flip side, a low body temperature can be indicative of a low thyroid and at the very least indicates a slow metabolism. Considering that the body reacts to calorie restriction by lowering metabolism, I don't suppose it should come as a surpise that CR mice have a low body temperature. ;)

Resveratrol (Red Wine extract) lowered my temperature even more after I started to take it.

EDIT: More significant if I take it about 30-45 minutes prior to eating my meals.

Lisa, a slower metabolism is probably what makes us live longer. Of course, it also makes us lose weight slower. So maybe we'd best turn up the heat until we get to goal, and then turn off the heat.

We were taught that a 10 degree Cenlsius increase in temperature doubles the rate of reaction of most enzymes. So if your body temp went from 37C to 27C (a little above room temp) you would presumably "go" twice as slow.

Did the old-time Inuit live to a very old age? Seems that their LC lifestyle, coupled with living in a cold climate, might have been an optimum lifestyle. Though I think they managed to keep toasty warm for the most part if I recall Steffansen's descriptionis correctly.

Were these CR mice? I thought they were just regular Ad Lib mice with genetically lower temperatures.

They were not CR mice.

There was a post by somone on the CR list about temperature and cancer. In Rats when they are CR'd temperature drops, but when the environment is heated and their body temperature is brought back to ad lib, they experience the same cancer rates as ad lib :lol:

Never felt so good to be colder!

Now, what I'd like to know is what factor made cooler. Low levels of thyroid? Low levels of cortisol? Or having cool sunglasses?

I like the picture of your "cool" mouse. :D