Immune cell betrayal explains why it gets colder as we age

Human evolution has provided us some protection from the existential threat of cold temperatures through our capacity to produce heat from fat stored in the body.

 

But as we age, we become more susceptible to cold and to inflammation and metabolic problems, which can lead to a host of chronic diseases.

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Researchers at Yale and the University of California-San Francisco (UCSF) have found a reason why this happens — a diminished supply of the very immune cells within fat that are designed to protect us from the cold.

 

In a new study, the researchers found that as mice age their fat tissue loses the immune cell group 2 innate lymphoid cells (ILC2) that restore body heat in presence of cold temperatures. But in a cautionary tale for those seeking easy treatments for diseases of ageing, the researchers also found that stimulating production of new ILC2 cells in ageing mice actually made them more prone to cold-induced death.

 

“What is good for you when you are young, can become detrimental to you as you age,” said Vishwa Deep Dixit, the Waldemar Von Zedtwitz Professor of Comparative Medicine and of Immunobiology and co-corresponding author of the study.

 

The results are published Sept. 1 in the journal Cell Metabolism.

 

Dixit and former colleague Emily Goldberg, now an assistant professor at UCSF, were curious about why fat tissue harbours immune system cells, which are usually concentrated in areas often exposed to pathogens, such as nasal passages, lungs, and skin. When they sequenced genes from cells of old and young mice they found that older animals lacked ILC2 cells, a deficit limiting their ability to burn fat and raise their body temperature in cold conditions.

 

When scientists introduced a molecule that boosts the production of ILC2 in ageing mice, the immune system cells were restored but, surprisingly, the mice were even more intolerant of cold temperatures.

 

“The simple assumption is that if we restore something that is lost, then we are also going to restore life back to normal,” Dixit said. “But that is not what happened. Instead of expanding healthy cells of youth, the growth factor ended up multiplying the bad ILC2 cells that remained in the fat of old mice.”

 

Yet when researchers took ILC2 cells from younger mice and transplanted them into older mice, they found, the older animals’ ability to tolerate cold was restored.

 

“Immune cells play a role beyond just pathogen defence and help maintain normal metabolic functions of life,” Dixit said. “With age, the immune system has already changed and we need to be careful how we manipulate it to restore the health of elderly.”

 

17 September 2021.