Slower Heat Response in Thermogenic Fat Helps Explain Greater Cold Sensitivity with Age

Cold sensitivity tends to increase as people age, and a team at City of Hope has identified a biological reason. Their study, published in Nature, centers on thermogenic fat. Unlike white fat, which mainly stores energy, this type of body fat burns calories to generate heat and keeps us warm. Its activity typically declines over time, which may account for why older adults feel the cold more.

Corresponding author “Annabel” Wang and her colleagues show that signals from nerves and immune cells set how much heat thermogenic fat releases by shifting the balance between highly active and less active fat cells.

The work builds on an earlier City of Hope finding that thermogenic fat cells differ in output. Some carry high levels of UCP1, a heat-generating protein, while others carry less and stay quieter. The team saw a similar mix in human thermogenic fat samples, though most of the experiments were done in mice.

This mixture may give the body a built-in way to adapt to changing temperatures. When extra warmth is needed, the nervous and immune systems signal the quieter cells to produce more heat, and once the need passes, that activity can be turned back down.

In older mice, that response was sluggish. Their thermogenic fat could still ramp up heat production, but it took longer, and the animals struggled more to hold their body temperature in the cold.

By blocking one part of the pathway behind this slowdown, the researchers restored some heat production in the older mice. Treated animals generated more heat and burned more energy. The drug used, mifepristone, acts on many parts of the body, so it is not a treatment for age-related cold sensitivity. Still, the results suggest the decline in thermogenic fat activity could be reversed.

“Learning how the body controls this process may offer insights into obesity, type 2 diabetes and other metabolic disorders,” said Wang. 

She sees the finding as relevant beyond keeping warm. 

“That possibility matters for more than staying warm,” Wang added. “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.”