Researchers have discovered genetic program that
promotes longevity in cold environments
Feb. 14, 2013 - Scientists have known for nearly a
century that cold-blooded animals, such as worms, flies and fish all
live longer in cold environments, but have not known exactly why. Even
lowering the body temperature of mice can mysteriously extend their lifespan.
Researchers at the University of Michigan Life
Sciences Institute have identified a genetic program that promotes
longevity of roundworms in cold environments - and this genetic program
also exists in warm-blooded animals, including humans.
"This raises the intriguing possibility that
exposure to cold air—or pharmacological stimulation of the
cold-sensitive genetic program—may promote longevity in mammals," said
Shawn Xu, LSI faculty member and the Bernard W. Agranoff Collegiate
Professor in the Life Sciences at the U-M Medical School.
The research was published online Feb. 14 in the
Scientists had long assumed that animals live
longer in cold environments because of a passive thermodynamic process,
reasoning that low temperatures reduce the rate of chemical reactions
and thereby slow the rate of aging.
"But now, at least in roundworms, the extended
lifespan observed at low temperature cannot be simply explained by a
reduced rate of chemical reactions," Xu said. "It's, in fact, an active
process that is regulated by genes."
Xu found that cold air activates a receptor known
as the TRPA1 channel, found in nerve and fat cells in nematodes, and
TRPA1 then passes calcium into cells. The resulting chain of signaling
ultimately reaches DAF-16/FOXO, a gene associated with longevity. Mutant
worms that lacked TRPA1 had shorter life spans at lower temperatures.
Because the mechanisms identified by Xu and his
collaborators also exist in a range of other organisms, including
humans, the research suggests that a similar effect might be possible.
The study also links calcium signaling to longevity for the first time
and makes a novel connection between fat tissue and temperature
Researchers have known that lowering the core body
temperature of warm-blooded animals, such as mice, by 0.9 degrees
Fahrenheit can extend lifespan by 20 percent, but it hasn't been
practical for humans to attempt to lower the core body temperature, Xu
"But if some aspects of the aging process are
initiated in skin and fat cells in humans as they are in nematodes,
should we go out to embrace some cold air in the winter?" Xu said.
Xu added that in addition to cool temperatures, the
spicy condiment wasabi activates TRPA1 as well, and that feeding wasabi
to nematodes increases their life spans. "Maybe we should be going to
sushi restaurants more often," he said.
Xu is a faculty member in the U-M Life Sciences
Institute, where his laboratory is located and all his research is
conducted. He is also an associate professor in the Department of
Molecular and Integrative Physiology at the U-M Medical School.
Other authors on the paper were Rui Xiao and
Yongming Dong of the Life Sciences Institute; Bi Zhang and Jianke Gong
of the Life Sciences Institute and the College of Life Science and
Technology at the Huazhong University of Science and Technology; Tao Xu
of the College of Life Science and Technology at the Huazhong University
of Science and Technology and the Institute of Biophysics, Chinese
Academy of Sciences; and Jianfeng Liu of the College of Life Science and
Technology at the Huazhong University of Science and Technology.
This work was supported by the Program of
Introducing Talents of Discipline to Universities from the Ministry of
Education of China, the National Natural Science Foundation of China,
and the National Institute of General Medical Sciences and National
Institute of Aging, both of the National Institutes of Health.