Healthcare (Commonwealth Union) – It is well known that many of us see our waistlines grow during middle age, but the concern goes beyond appearances. Abdominal fat speeds up the aging process and slows metabolism, raising the likelihood of developing diabetes, cardiovascular issues, and other long-term illnesses. Still, the exact mechanisms by which age turns toned abs into a softer midsection have remained unclear.
Now, preclinical research from City of Hope — one of the largest and most advanced cancer and disease research institutions in the U.S., and a leader in diabetes research — has identified the cellular trigger behind age-related belly fat. These new findings, published today in Science, offer a fresh perspective on why midsection weight gain is common in middle age and point to a possible new approach for preventing it and improving healthy aging.
Qiong (Annabel) Wang, Ph.D. co-lead author of the study and associate professor of molecular and cellular endocrinology at City of Hope’s Arthur Riggs Diabetes & Metabolism Research Institute, indicated that as people get older, they tend to lose muscle mass and accumulate fat — even if their overall weight doesn’t change. She also stated that they found that aging introduces a new form of adult stem cell and significantly increases the production of fat cells, particularly in the abdominal region.
Working alongside the UCLA lab of co-corresponding author Xia Yang, Ph.D., researchers carried out a series of mouse-based experiments, later confirming their findings using human cells. Wang and her team concentrated on white adipose tissue (WAT), the type of fat linked to weight gain as people age.
Although it’s widely understood that fat cells enlarge over time, the researchers proposed that WAT might also expand by generating entirely new fat cells — suggesting it could grow without limit.
To investigate this theory, they examined adipocyte progenitor cells (APCs), a category of stem cells within WAT that develop into fat cells.
The team at City of Hope began by transplanting APCs from both young and old mice into a second group of young mice. Remarkably, the APCs from older mice quickly produced a massive number of new fat cells.
However, when APCs from young mice were introduced into older mice, the cells created far fewer new fat cells. These results demonstrated that aging APCs have an inherent ability to produce fat cells, independent of the age of the organism they are placed in.
With the application of single-cell RNA sequencing, the researchers made a contrast of APC gene activity in young and older mice. In young mice, the APCs were mostly inactive, but in middle-aged mice, they became highly active and began rapidly producing new fat cells.
Adolfo Garcia-Ocana, Ph.D., the Ruth B. & Robert K. Lanman Endowed Chair in Gene Regulation & Drug Discovery Research and chair of the Department of Molecular & Cellular Endocrinology at City of Hope, indicated that while most adult stem cells lose their ability to grow as we age, APCs behave differently — aging actually boosts their ability to multiply and spread. He pointed out that this is the first time they have seen clear evidence that age-related belly fat growth is driven by APCs generating more fat cells.
Researchers noted that as mice aged, their APCs changed into a newly identified type of stem cell known as committed preadipocytes, age-specific (CP-As). These CP-A cells emerge in middle age and are highly active in producing new fat cells, helping explain the weight gain seen in older mice.
They further discovered that a signaling pathway called the leukemia inhibitory factor receptor (LIFR) plays a key role in driving CP-A cells to multiply and mature into fat cells.
“We discovered that the body’s fat-making process is driven by LIFR. While young mice don’t require this signal to make fat, older mice do,” said Wang. “Our research indicates that LIFR plays a crucial role in triggering CP-As to create new fat cells and expand belly fat in older mice.”
