Restoring safe fat storage and heat production in aging adipose tissue: a review in Science
Restoring safe fat storage and heat production in aging adipose tissue: a review in Science
On 5 November, Karima Drareni and Patrick Seale of the University of Pennsylvania published a review of adipose tissue plasticity in Science, examining how this tissue adapts to the body's needs. With age, fat around internal organs can expand, while subcutaneous fat becomes less able to renew itself and adipose tissue produces less heat.
After a meal, adipose tissue stores excess energy and releases it to other organs between meals. When nutrient intake remains high over time, the formation of new fat cells helps distribute fat among small, functional cells. As the tissue grows, it needs more blood vessels, while signals from nerves and immune cells regulate fat storage and use. When fat cells become overloaded, the blood supply fails to keep pace, and inflammation and scarring increase, the cells become less able to retain fat, which accumulates in the liver and muscles. In lipodystrophies, disorders involving a shortage of adipose tissue, impaired fat storage can also lead to fat accumulation in the liver and diabetes.
The ability to form new fat cells changes differently with age in different parts of the body. It declines in subcutaneous fat, whereas fat around internal organs can expand substantially in middle age. In one of the experiments in mice, researchers collected equal numbers of progenitor cells capable of becoming fat cells from the fat surrounding internal organs in young and one-year-old males. They transplanted these cells into the subcutaneous fat of young mice to compare the donor cells under the same conditions. Over a month, progenitor cells from one-year-old mice produced approximately 2,5 times as many fat cells as those from young mice. Cells from 18-month-old donors, however, produced fewer fat cells than cells from young mice.
A study of human subcutaneous fat compared ten people aged 30 or younger with ten aged 65 or older who had comparable body mass indices. In the older group, genes associated with inflammation and scar tissue formation were more active in fat cells, their progenitor cells, and blood vessel cells.
Some fat cells use energy to generate body heat, and immune cells support this activity. In experiments in old mice, researchers found a decline in ILC2, immune cells that support heat production in adipose tissue. They attempted to restore ILC2 numbers using IL-33, a signaling protein that supports ILC2 survival. The remaining aged ILC2 multiplied, but old males given IL-33 had lower survival during cold exposure than controls. To test the role of age-related changes in ILC2 themselves, the researchers conducted another experiment in which they transferred ILC2 from adult females into old females. The transfer helped the old females survive cold exposure.
Weight loss reduces the burden on adipose tissue. Drareni and Seale consider the inflammation and scarring that persist afterward to be additional treatment targets. They propose interventions that help the tissue store and use fat safely by supporting its blood supply and immune cell function. The appropriate target depends on which function is impaired: subcutaneous fat may need support for new fat cell formation, while heat-producing tissue may need its immune cell function restored.