The body’s inner heater weakens with age, but experiments in older mice suggest it can be turned back up.
As we age, staying warm can become more difficult, but the reason may go beyond changes in circulation or muscle mass. Deep inside the body, a specialized type of fat acts like a built-in heater, burning calories to produce warmth when temperatures drop. Over time, however, this system becomes less responsive, potentially affecting not only how the body handles cold but also how it uses energy.
Now, researchers at City of Hope have uncovered a biological mechanism that helps explain why this natural heating system slows with age. Their study, published in Nature, reveals how communication between nerves, immune cells, and heat-producing fat changes over time.
“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., the study’s corresponding author and an associate professor at City of Hope’s Arthur Riggs Diabetes & Metabolism Research Institute.
How Fat Turns Up The Heat
The body’s heat-producing fat contains cells with different levels of activity. Previous City of Hope research found that some have abundant UCP1, a protein that generates heat, while others contain less and produce less warmth. The new study identified a similar mixture in human thermogenic fat samples, although most experiments were conducted in mice.
That mixture appears to give the body a reserve of heating capacity. When temperatures fall, nerve and immune signals encourage less active cells to increase their heat output. When the demand for warmth eases, the system can reduce that activity again.
In older mice, this adjustment became sluggish. Their thermogenic fat retained the ability to produce more heat but took longer to respond, making it harder for the animals to maintain their body temperature during cold exposure.
Restoring Heat Production In Older Mice
The researchers then tested whether they could interrupt the pathway behind that delayed response. Using the drug mifepristone to block one part of the pathway restored some heat production in older mice. The animals generated more warmth and burned more energy. The finding suggests that at least some of the decline in thermogenic fat function may be reversible.
“That possibility matters for more than staying warm,” Wang 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.”
Reference: “Bistable regulation of adipocyte heterogeneity governs thermogenesis” by Anying Song, Yifan Wang, Guan Wang, Marie Bae, Zhichao Wang, Guoming Gao, Zhuyin Wu, Geming Lu, Jieyi Meng, Jiayu Yu, Soojin Park, Adolfo Garcia-Ocaña, Patrick T. Fueger, Loredana Rao, Andrea Frontini, Yong Liu, Lei Jiang, Yi Zhu and Qiong A. Wang, 11 November 2026, Nature.
DOI: 10.1038/s41586-026-11308-7
This study was funded by NIH/National Institutes of Health, the Caltech-City of Hope Biomedical Research Initiative Grant, the City of Hope startup, and salary-saving funds.
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