"Our study shows it is possible to increase lifespan in mice by modest but prolonged lowering of core body temperature," said Bruno Conti, an associate professor at Scripps Research who led the study. "This longer lifespan was attained independent of calorie restriction."
Prior to this study, researchers had known that core body temperature and aging were related in cold-blooded animals. Scientists had also known that lifespan could be extended in warm-blooded animals by reducing the number of calories they consumed, which also lowered core body temperature. But the degree of calorie restriction needed to extend lifespan is not easy to achieve, even in mice.
Prior to the current study, critical questions about the relation between calorie restriction, core body temperature, and lifespan remained unanswered. Was calorie restriction itself responsible for longer lifespan, with reduced body temperature simply a consequence? Or was the reduction of core body temperature a key contributor to the beneficial effects of calorie restriction? Conti and colleagues wanted to find out.
To tackle the problem, the scientists decided to try to lower core body temperature directly, without restricting food intake. In cold-blooded animals, such as roundworms (C. elegans) and fruitflies (Drosophila), this task is straight-forward--core body temperature can be lowered simply by changing the temperature of the environment. But for warm-blooded animals, the task is much more challenging.
Conti and colleagues decided to focus their efforts on the preoptic area of the hypothalamus, a structure in the brain that acts as the body's thermostat and is crucial to temperature regulation. Just as holding something warm near the thermostat in a room can fool it into thinking that the entire room is hotter so that the air conditioning turns on, the Scripps Research team reasoned that they could reset the brain's thermostat by producing heat nearby.
To do so, they created a mouse model that produced large quantities of uncoupling protein 2 in hypocretin neurons in the lateral hypothalamus, which is near the preoptic area. The action of uncoupling protein 2 produced heat, which diffused to other brain structures, including the preoptic area. And, indeed, the extra heat worked to induce a continuous reduction of the core body temperature of the mice, lowering it from 0.3 to 0.5 degrees Celsius.
The scientists were then able to measure the effect of lowered core body temperature on lifespan, finding that the mice with lowered core body temperature had significantly longer median lifespan than those that didn't. While this effect was observed in both males and females, in this study the change was more pronounced in females-median lifespan was extended about 20 percent in females and about 12 percent in males.
The researchers performed several experiments to make sure that other factors were not contributing to the lowered core body temperature. They confirmed that the experimental mice were normal in their ability to generate fever, and that these mice moved around about the same amount as normal mice. In addition, the researchers verified that the hypocretin neurons producing uncoupling protein 2 were not involved in temperature regulation.
Importantly, the mice in this study were allowed to eat as much food as they wished, and the experimental and control mice ate the same amount. The weight of the female experimental and control mice did not differ significantly. However, experimental male mice weighed about 10 percent more than the control group, most likely reflecting the reduced energy required to maintain a lower core body temperature, according to the paper.
"Our model addresses something more basic than the amount of food," said Tamas Bartfai, who is chair of the Molecular and Integrative Neurosciences Department, director of the Harold L. Dorris Neurological Research Center at Scripps Research, and an author of the paper. "It works at the level of the thermoregulatory set point that is governed by intra-brain temperature and neurotransmitters. This mechanism, we believe, will be a good target for pharmacological manipulation or heating."
The idea to manipulate the temperature set-point came when Conti and Bartfai joined Scripps Research in the year 2000. Both scientists share common interests in neuroimmunology and the mechanisms of fever. It took over five years of work to conclude this study.
The researchers are now working to identify the precise mechanisms that are responsible for the beneficial effects of reduced core body temperature. They are also investigating whether their findings can be applied to research on obesity.
Keith McKeown | EurekAlert!
The end of pneumonia? New vaccine offers hope
23.10.2017 | University at Buffalo
Scientists track ovarian cancers to site of origin: Fallopian tubes
23.10.2017 | Johns Hopkins Medicine
Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
23.10.2017 | Event News
17.10.2017 | Event News
10.10.2017 | Event News
23.10.2017 | Life Sciences
23.10.2017 | Physics and Astronomy
23.10.2017 | Health and Medicine