Understanding Age-Related Belly Fat

As people age, a common phenomenon occurs: the waistline gradually expands, even when overall body weight remains relatively stable. This increase in abdominal fat is more than a cosmetic concern, as excess belly fat has been linked to slower metabolism, accelerated aging, type 2 diabetes, heart disease, and other chronic health problems.

Scientists have long known that body composition changes with age, but exactly why fat tends to accumulate around the midsection has remained unclear. Now, researchers at City of Hope have identified what may be a key biological driver of age-related belly fat.

Newly Identified Stem Cell Population

The research team discovered a newly identified type of stem cell called committed preadipocytes, age-specific (CP-As), which appears during aging and may help fuel the production of new fat cells. The emergence of these cells may help explain why older mice gained more fat as they aged.

The researchers found that aging did more than simply activate CP-As. As mice reached middle age, some CP-As transformed into a new stem cell population, which proved especially effective at producing new fat cells. Their investigation focused on white adipose tissue (WAT), the body’s primary fat-storage tissue.

White adipose tissue is responsible for storing excess energy and is a major contributor to weight gain and belly fat accumulation. The scientists have long known that existing fat cells can become larger as people age. However, the researchers suspected that another process might also be contributing to expanding waistlines: the creation of entirely new fat cells.

Key Findings

To test this idea, the team studied adipocyte progenitor cells (APCs), a type of stem cell found within fat tissue. These cells serve as precursors that can mature into fully developed fat cells. The researchers transplanted APCs from both young and older mice into a separate group of young mice.

The results were striking. APCs taken from older animals generated large numbers of new fat cells. The opposite experiment produced a very different outcome. When APCs from young mice were transplanted into older mice, they generated relatively few new fat cells.

This suggested that the ability to aggressively produce fat was built into the older APCs themselves and did not depend on the age of the animal receiving them. To understand what was happening at a molecular level, the researchers used single-cell RNA sequencing, a technique that allows scientists to examine gene activity in individual cells.

Human Relevance

The analysis revealed that APCs were relatively quiet in young mice. In middle-aged mice, however, these cells became highly active and began producing large numbers of new fat cells. While most adult stem cells’ capacity to grow wanes with age, the opposite holds true with APCs — aging unlocks these cells’ power to evolve and spread.

The researchers found that the body’s fat-making process is driven by a signaling pathway known as leukemia inhibitory factor receptor (LIFR). Signaling pathways are communication systems that allow cells to receive instructions and coordinate their behavior. In this case, LIFR appeared to play a major role in helping CP-A cells multiply and develop into fat cells.

To determine whether the findings might apply beyond mice, the team analyzed human tissue samples from people of different ages using the same single-cell RNA sequencing approach. The researchers identified cells that closely resembled the newly discovered CP-As. These cells were found in greater numbers in tissue from middle-aged individuals.

The human CP-As also showed a strong ability to generate new fat cells, suggesting that a similar biological process may occur in people. Understanding the role of CP-As in metabolic disorders and how these cells emerge during aging could lead to new medical solutions for reducing belly fat and improving health and longevity.