As people age, many notice a familiar shift: their waistlines tend to expand, even if their overall weight remains fairly stable. This increase in belly fat goes beyond mere aesthetics. In fact, excess abdominal fat is associated with a slower metabolism, accelerated aging, type 2 diabetes, heart disease, and other long-term health issues.
Researchers have understood for a while that body composition alters with age, but the specific reasons behind the accumulation of fat around the midsection have been somewhat elusive.
Now, a team at City of Hope has pinpointed what might be a significant biological factor driving age-related belly fat. Their study, featured in the journal Science, identifies a new type of stem cell that emerges with aging and may contribute to the formation of new fat cells. This discovery could eventually lead to innovative methods for reducing abdominal fat and enhancing healthy aging.
“As people age, they often lose muscle and gain fat, even if their body weight stays the same,” stated Qiong (Annabel) Wang, Ph.D., a co-author of the study and associate professor at City of Hope’s Arthur Riggs Diabetes & Metabolism Research Institute. “We found that aging prompts the emergence of a new kind of adult stem cell that boosts the body’s production of new fat cells, particularly around the abdomen.”
Exploring Beyond Enlarged Fat Cells
The research team collaborated with scientists at UCLA and carried out a variety of experiments on mice, later supported by research involving human cells.
They focused on white adipose tissue (WAT), which is the body’s primary fat-storage tissue. This tissue plays a crucial role in storing extra energy and is a major factor in weight gain and the buildup of belly fat.
While it’s well-known that existing fat cells can increase in size over time, the researchers suspected that the creation of entirely new fat cells might also be a factor in expanding waistlines.
If that’s the case, it suggests that aging fat tissue could continue to grow not just by enlarging what’s already there but by consistently adding new cells.
To investigate this, the team looked into adipocyte progenitor cells (APCs), a type of stem cell present in fat tissue. These cells can develop into fully formed fat cells.
Older Stem Cells Produced Far More Fat
The researchers transplanted APCs from both younger and older mice into a different group of young mice.
The results were noteworthy: APCs from older mice produced a significant number of new fat cells.
In contrast, when APCs from young mice were transplanted into older mice, they generated relatively few new fat cells.
This indicated that the capacity to produce fat aggressively was inherent to the older APCs and not reliant on the age of the recipient mice.
To delve into the molecular mechanisms at play, the researchers utilized single-cell RNA sequencing to assess gene activity in individual cells.
The analysis showed that APCs were relatively inactive in young mice. However, in middle-aged mice, these cells became much more active, leading to the production of a large quantity of new fat cells.
“Unlike most adult stem cells, which lose their growth capacity with age, APCs gain the ability to proliferate and expand as they age,” noted Adolfo Garcia-Ocana, Ph.D., who chairs the Department of Molecular & Cellular Endocrinology at City of Hope. “This is the first evidence linking the expansion of our abdominal area to the high output of new fat cells from APCs as we age.”
Uncovering a New Age-Related Stem Cell
The research revealed that aging activates not just APCs but also leads to a transformation of some of these cells into a newly identified population called committed preadipocytes, or CP-As.
This new cell type appears specifically with aging and proves quite effective at generating fat cells. Their emergence may explain why older mice tend to accumulate more fat as they get older.
The researchers then sought to identify the biological signals governing this process.
They discovered a crucial signaling pathway known as leukemia inhibitory factor receptor (LIFR), which appears significant in directing CP-A cells to multiply and evolve into fat cells.
“We found that the fat production process is guided by LIFR. While young mice can produce fat without this signal, older mice rely on it,” Wang explained. “Our research indicates that LIFR is vital for activating CP-As to create new fat cells and accumulate abdominal fat in older mice.”
Similar Fat-Producing Cells Found in Humans
To investigate whether these findings might extend to humans, the team analyzed tissue samples from individuals of various ages, applying the same single-cell RNA sequencing methodology.
They identified cells resembling the newly discovered CP-As, and these were found in greater abundance in samples from middle-aged individuals.
These human CP-As also demonstrated a strong capability to generate new fat cells, hinting that a similar biological mechanism could be at play in humans.
“Our results underscore the need to manage the formation of new fat cells to combat age-related obesity,” Wang remarked. “Grasping the role of CP-As in metabolic disorders and their emergence during aging might lead to innovative medical approaches for reducing belly fat and enhancing health and longevity.”
A Potential New Target for Age-Related Obesity
While further research is necessary, the findings present scientists with an exciting new target for future therapies.
Researchers plan to monitor CP-A cells in animal studies, examine their behavior in humans, and explore methods to block or eliminate them. If successful, such strategies could help mitigate the belly fat accumulation often seen with aging.
