New Haven, Connecticut, USA: A team at Yale School of Medicine, led by Indian-origin scientist Vishwa Deep Dixit, has uncovered how a unique group of immune cells shifts with age, offering new insights into chronic inflammation and its connection to aging. The research was published this month in Nature Aging.
The study revealed that a specific type of macrophages, known as nerve-associated macrophages (NAMs), play a role in regulating fat metabolism and controlling age-related inflammation. Over time, these NAMs decrease, while a different type, called age-associated macrophages (AAMs), appears in older subjects.
“When we discovered these macrophages in fat tissue contained unusually high levels of neurotransmitters, we wondered what their role was and whether it changes with age,” Dixit, the Waldemar Von Zedtwitz Professor of Pathology and senior author of the study, explained to Yale.
Researchers analyzed fat tissue from both young and old mice, using imaging and genetic sequencing to identify 13 distinct macrophage subtypes, including NAMs and AAMs. The AAMs were present only in older animals and showed elevated inflammatory markers, suggesting they contribute to inflammaging.
“We identified 13 different macrophage types, each with unique cellular mechanisms,” Dixit said. “As a bonus, we also discovered cells that were previously unknown.”
Claire Leveau, a postdoctoral fellow in Dixit’s lab and co-author, noted the team initially knew very little about these macrophages. “We had to lay a lot of groundwork because there was so much we didn’t know,” she said.
The study also demonstrated that removing NAMs in older animals worsened tissue decline, impaired fat breakdown, and increased chronic inflammation.
“Understanding how these macrophages evolve with age allows us to explore ways to preserve the beneficial ones and prevent harmful, age-associated types from emerging,” Dixit said. “If successful, we could reduce tissue decline while aging continues naturally.”
The discovery emphasizes the complex interaction between nerves and immune cells across a lifespan. Dixit commented, “This is just the beginning of understanding the intricate biology of aging and how nerves and macrophages communicate.
