Researchers find answer to an age-old question

Abstract: Research by City of Hope, a cancer research and treatment organization, provides new insights into why midsections widen with middle age. According to Dr. Qiong Wang, co-author of a new study, “people often lose muscle and gain body fat as they age – even when their body weight remains the same. We discovered aging triggers the arrival of a new type of adult stem cell and enhances the body’s massive production of new fat cells, especially around the belly.”

New research by City of Hope, a cancer research and treatment organization based in Los Angeles, appears to have “uncovered the cellular culprit behind age-related abdominal fat, providing new insights into why midsections widen with middle age.

The findings, which were published recently in the research publication Science, suggest a “novel target for future therapies to prevent belly flab and extend our healthy lifespans.”

“It’s no secret that our waistlines often expand in middle-age, but the problem isn’t strictly cosmetic,” a release from the facility states. “Belly fat accelerates aging and slows down metabolism, increasing our risk for developing diabetes, heart problems and other chronic diseases. Exactly how age transforms a six pack into a softer stomach, however, is murky.”

According to Dr. Qiong Wang, the study’s co-author, “people often lose muscle and gain body fat as they age – even when their body weight remains the same. We discovered aging triggers the arrival of a new type of adult stem cell and enhances the body’s massive production of new fat cells, especially around the belly.”

In collaboration with the UCLA laboratory co-author Dr. Xia Yang, the scientists conducted a series of mouse experiments later validated on human cells. Wang and her colleagues focused on white adipose tissue (WAT), the fatty tissue responsible for age-related weight gain, the release stated.

“While it’s well-known that fat cells grow larger with age, the scientists suspected that WAT also expanded by producing new fat cells, meaning it may have an unlimited potential to grow,” it said.

To test their hypothesis, the researchers focused on adipocyte progenitor cells (APCs), a group of stem cells in WAT that evolve into fat cells, the release said.

The City of Hope team, it stated,, “first transplanted APCs from young and older mice into a second group of young mice. The APCs from the older animals rapidly generated a colossal amount of fat cells.

“When the team transplanted APCs from young mice into the older mice, however, the stem cells did not manufacture many new fat cells. The results confirmed that older APCs are equipped to independently make new fat cells, regardless of their host’s age.”

Using single-cell RNA sequencing, the scientists next compared APC gene activity in young and older mice. While barely active in young mice, APCs woke up with a vengeance in middle-aged mice and began pumping out new fat cells.

Dr. Adolfo Garcia-Ocana, chair of the Department of Molecular & Cellular Endocrinology at City of Hope, said that “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.

“This is the first evidence that our bellies expand with age due to the APCs’ high output of new fat cells.”

Aging, the researchers said also transformed the APCs into a new type of stem cell called committed preadipocytes, age-specific (CP-As). Arising in middle age, CP-A cells actively churn out new fat cells, explaining why older mice gain more weight.

A signaling pathway called leukemia inhibitory factor receptor (LIFR) proved critical for promoting these CP-A cells to multiply and evolve into fat cells, they said.

“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.”