LOS ANGELES — Researchers from City of Hope ® , one of the largest and most advanced cancer research and treatment organizations in the country, have uncovered the biological reason for why we become more sensitive to cold as we get older.
Unlike white fat, which primarily stores energy, thermogenic fat is a special type of body fat that burns calories to produce heat and helps us stay warm. Thermogenic fat tends to become less active with age, which may explain why older people are more sensitive to cold.
"Learning how the body controls this process may offer insights into obesity, type 2 diabetes and other metabolic disorders," said Qiong "Annabel" Wang, Ph.D., an associate professor at City of Hope’s Arthur Riggs Diabetes & Metabolism Research Institute and corresponding author of the new Nature study.
Her research reveals how signals from nerves and immune cells control how much heat thermogenic fat produces by changing the balance between highly active and less active fat cells.
Experiments in mice suggest that this system becomes less flexible with age, leaving thermogenic fat slower to respond when temperatures fall.
Previously, City of Hope researchers found that thermogenic fat cells vary in how much heat they produce. Some have high levels of UCP1, a protein that generates heat, while others have less UCP1 and remain less active. In this study, City of Hope researchers observed a similar mix in human thermogenic fat samples, although they conducted most of our experiments in mice.
How the Body Turns Up the Heat
This mix of thermogenic fat cells may give the body a built-in way to adjust to changing temperatures. When more warmth is needed, signals from the nervous and immune systems prompt less-active cells to increase heat production. When the need passes, the system can dial that activity back.
In older mice, however, this response became sluggish. Their thermogenic fat could still increase heat production, but it took longer. As a result, the animals had more difficulty maintaining their body temperature during cold exposure.
The researchers were able to restore some heat production in older mice by blocking one part of the biological pathway behind this slowdown. The treated animals produced more heat and burned more energy.
The drug used in the experiment, mifepristone, affects many parts of the body, so it is not a treatment for age-related cold sensitivity. But the results suggest that the decline in thermogenic fat activity could be reversed.
"That possibility matters for more than staying warm," Qiong said. "Thermogenic fat also burns glucose and fat, and its activity tends to decline with age. If scientists can find a safe, precise way to restore that activity, this foundational research could eventually deepen our understanding of age-related metabolic problems, including obesity and type 2 diabetes."
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The study “Bistable regulation of adipocyte heterogeneity governs thermogenesis” was supported by the City of Hope startup and salary-saving funds, the Caltech-City of Hope Biomedical Research Initiative Grant and the National Institutes of Health (P30CA033572).
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About City of Hope
City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the United States, and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines , as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked among the nation’s top cancer centers by U.S. News & World Report at its core, City of Hope’s uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope’s growing national system includes its Los Angeles campus, Orange County, California, campus, a network of clinical care locations across Southern California and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM . For more information about City of Hope, follow us on Facebook , X , YouTube , Instagram and LinkedIn .
Nature
Experimental study
Animals
Bistable regulation of adipocyte heterogeneity governs thermogenesis
11-Nov-2026