Expanding waistlines in the middle ages are not just a cosmetic problem; it brings belly fat with itself as well. Belly fat increases the risk of heart disease and slows down metabolism. Higher belly fat content also accelerates the aging process. Despite all this information, the actual reason why a six-pack turns to a soft stomach is not well understood. According to new research, aging triggers a surge in stem cell activity, leading to an increase in the production of belly fat. Aging leads to the emergence of new adult stem cells that stimulate the formation of new fat cells, particularly in the abdominal area. According to Qiong (Annabel) Wang, the study’s co-corresponding author and an associate professor of molecular and cellular endocrinology at City of Hope’s Arthur Riggs Diabetes & Metabolism Research Institute, we often lose muscle and gain fat as we age. Our body weight remains the same despite such biochemical changes occurring in our bodies.
Preclinical research by City of Hope®, one of the largest and most advanced cancer research and treatment organizations in the United States and a leading research center for diabetes and other life-threatening illnesses, is shedding new light on how our waists widen as we head into middle age, due to cellular causes. Their observations suggest targeting novel targets for future therapies to prevent belly flab and extend lifespans.
Together with the UCLA laboratory co-corresponding author Xia Yang, Ph.D., the scientists performed a series of mouse experiments later validated on human cells. They are primarily focused on white adipose tissue (WAT), which is associated with age-related weight gain. It is already known that fat cells increase in size with age, but new observations also suggest that white adipose tissue (WAT) expands by producing new fat cells, which have the potential to proliferate indefinitely. To test their hypothesis, they focused on adipocyte progenitor cells (APCs), a type of stem cell found in white adipose tissue (WAT) that differentiates into fat cells.
The City of Hope team transplanted APCs from older and young mice into a group of young mice. The APCs from the older mice rapidly gave rise to a huge number of fat cells. However, when younger APCs were transplanted to older mice, the stem cells failed to generate as many new fat cells. The observations confirmed that older APCs are capable of independently developing new fat cells, regardless of their host’s age. Using single-cell RNA sequencing, the team also found enormous differences in the activity of younger APCs compared to older ones. Older APCs churned out many more new fat cells in middle-aged mice than younger ones.
While most stem cells lose their ability to grow further with age, in the case of APCs, the reverse is true—aging actually makes them grow faster and more effectively. This is also the first record of APC’s high output of new fat cells being responsible for expanding bellies and waistlines.
Aging also converted the APCs into a new type of stem cell called committed preadipocytes, age-specific (CP-As). CP-A cells rapidly generate new fat cells, which explains why older mice tend to gain more weight. The leukemia inhibitory factor receptor (LIFR), a component of a signalling pathway, is vital in promoting the multiplication and differentiation of CP-A cells into fat cells. While unimportant in younger mice, LIFR is crucial in older mice to generate belly fat and new fat cells.
Next, utilizing single-cell RNA sequencing on samples from people of various ages, Wang and her colleagues studied APCs from human tissue in the lab. The team also identified an increase in the formation of similar CP-A cells in middle-aged people. Just as CP-As in mice, their discovery suggests that CP-As in humans play a similar role in creating new fat cells.
The findings may play a significant role in developing methods to prevent or mitigate age-related fat gain. Future research will also involve tracking CP-A cells in animal models and recording the role of CP-A cells in humans.
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