Linking calorie restriction, body temperature and healthspan

Date:
September 8, 2020
Source:
Scripps Research Institute
Summary:
Cutting calories significantly may not be an easy task for most,
but it's tied to a host of health benefits ranging from longer
lifespan to a much lower chance of developing cancer, heart disease,
diabetes and neurodegenerative conditions such as Alzheimer's. A
new study illuminates the critical role that body temperature
plays in realizing these diet- induced health benefits.



FULL STORY ========================================================================== Cutting calories significantly may not be an easy task for most, but
it's tied to a host of health benefits ranging from longer lifespan to
a much lower chance of developing cancer, heart disease, diabetes and neurodegenerative conditions such as Alzheimer's.


==========================================================================
A new study from teams led by Scripps Research Professors Bruno Conti,
PhD, and Gary Siuzdak, PhD, illuminates the critical role that body
temperature plays in realizing these diet-induced health benefits. Through their findings, the scientists pave the way toward creating a medicinal compound that imitates the valuable effects of reduced body temperature.

The research appears in Science Signaling.

Making the cool connection Conti has spent years studying how and why
calorie restriction leads to better health, with the ultimate goal of translating the findings into medicines that can mimic what happens
naturally when a person eats less.

One consistent observation is that when mammals consume less food, their
body temperature drops. It's evolution's way of helping us conserve
energy until food is available again, Conti explains. It makes sense, considering that up to half of what we eat every day is turned into
energy simply to maintain our core body temperature.



========================================================================== Conti's previous work showed that temperature reduction can increase
lifespan independently of calorie restriction -- and that these effects
involve activation of certain cellular processes, most of which remain
to be identified.

On the flip side, studies have shown that preventing body temperature from dropping can actually counteract positive effects of calorie restriction.

Notably, in an experiment involving calorie-restricted mice, anti-cancer benefits were diminished when core body temperature remained the same.

"It's not easy to discern what's driving the beneficial changes of calorie restriction," Conti says. "Is it the reduced calories on their own, or
the change in body temperature that typically happens when one consumes
fewer calories? Or is it a combination of both?" Metabolites hold the
answer In the new research, Conti and his team designed an experiment
that would allow them to independently evaluate the effects of reduced nutrients and those of body temperature.



==========================================================================
They compared one group of calorie-restricted mice housed at room
temperature - - about 68 degrees Fahrenheit (22 degrees Celsius) to
another group housed at 86 degrees (30 degrees Celsius). The warmer
environment invoked "thermoneutrality," a state at which most animals
cannot easily reduce their body temperature.

The Siuzdak team, using a technology they developed called activity metabolomics, then evaluated the mice by measuring their metabolites,
or chemicals released by the animals' metabolism. Through this, they were
able to look for molecules in the bloodstream and in the brain that are
changed by the reduction of either nutrients or body temperature.

"The data we collected showed that temperature has an equal or greater
effect than nutrients on metabolism during calorie restriction," Conti
says. Notably, the team provided the first comprehensive profiling of
the metabolites that are changed by temperature reduction.

Through a computing analysis of results from both groups of mice, the scientists were able to prioritize which metabolites were most responsible
for triggering changes to core body temperature. In a separate experiment,
they also showed it is possible to administer certain metabolites as a
drug to affect body temperature.

Conti says further work to validate the changes induced by temperature
during calorie restriction should provide novel targets for future
medicines he calls "temperature mimetics," which could offer the health-promoting effects without having to reduce body temperature.


========================================================================== Story Source: Materials provided by Scripps_Research_Institute. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Carlos Guijas, J. Rafael Montenegro-Burke, Rigo Cintron-Colon,
Xavier
Domingo-Almenara, Manuel Sanchez-Alavez, Carlos A. Aguirre, Kokila
Shankar, Erica L.-W. Majumder, Elizabeth Billings, Bruno Conti,
Gary Siuzdak. Metabolic adaptation to calorie restriction. Science
Signaling, 2020; 13 (648): eabb2490 DOI: 10.1126/scisignal.abb2490 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200908170527.htm

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