Linking calorie restriction, body temperature and healthspan

September 08, 2020

LA JOLLA, CA--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.
-end-
The paper, "Metabolic adaptation to calorie restriction," was authored by 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 and Gary Siuzdak.

The research was supported by the National Institutes of Health [R01 GM114368-03, P30 MH062261-17, P01 DA026146-02 and GM113894], the NIH Cloud Credits Model Pilot (a component of the NIH Big Data to Knowledge program), the Skaggs Graduate School of Chemical and Biological Sciences and ARCS Foundation.

Scripps Research Institute

Related Heart Disease Articles from Brightsurf:

Cellular pathway of genetic heart disease similar to neurodegenerative disease
Research on a genetic heart disease has uncovered a new and unexpected mechanism for heart failure.

Mechanism linking gum disease to heart disease, other inflammatory conditions discovered
The link between periodontal (gum) disease and other inflammatory conditions such as heart disease and diabetes has long been established, but the mechanism behind that association has, until now, remained a mystery.

New 'atlas' of human heart cells first step toward precision treatments for heart disease
Scientists have for the first time documented all of the different cell types and genes expressed in the healthy human heart, in research published in the journal Nature.

With a heavy heart: How men and women develop heart disease differently
A new study by researchers from McGill University has uncovered that minerals causing aortic heart valve blockage in men and women are different, a discovery that could change how heart disease is diagnosed and treated.

Heart-healthy diets are naturally low in dietary cholesterol and can help to reduce the risk of heart disease and stroke
Eating a heart-healthy dietary pattern rich in vegetables, fruits, whole grains, low-fat dairy products, poultry, fish, legumes, vegetable oils and nuts, which is also limits salt, red and processed meats, refined-carbohydrates and added sugars, is relatively low in dietary cholesterol and supports healthy levels of artery-clogging LDL cholesterol.

Pacemakers can improve heart function in patients with chemotherapy-induced heart disease
Research has shown that treating chemotherapy-induced cardiomyopathy with commercially available cardiac resynchronization therapy (CRT) delivered through a surgically implanted defibrillator or pacemaker can significantly improve patient outcomes.

Arsenic in drinking water may change heart structure raising risk of heart disease
Drinking water that is contaminated with arsenic may lead to thickening of the heart's main pumping chamber in young adults, according to a new study by researchers at Columbia University Mailman School of Public Health.

New health calculator can help predict heart disease risk, estimate heart age
A new online health calculator can help people determine their risk of heart disease, as well as their heart age, accounting for sociodemographic factors such as ethnicity, sense of belonging and education, as well as health status and lifestyle behaviors.

Wide variation in rate of death between VA hospitals for patients with heart disease, heart failure
Death rates for veterans with ischemic heart disease and chronic heart failure varied widely across the Veterans Affairs (VA) health care system from 2010 to 2014, which could suggest differences in the quality of cardiovascular health care provided by VA medical centers.

Heart failure: The Alzheimer's disease of the heart?
Similar to how protein clumps build up in the brain in people with some neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, protein clumps appear to accumulate in the diseased hearts of mice and people with heart failure, according to a team led by Johns Hopkins University researchers.

Read More: Heart Disease News and Heart Disease Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.