Aging-linked stem cells may help drive belly fat, study finds
City of Hope researchers found age-specific precursor cells in mice and similar human cells that may spur new abdominal fat formation.
By Priya Raghavan · Science Reporter
3 min read
Researchers at City of Hope say they have identified a cellular process that may help explain why abdominal fat often rises with age. The finding points to a possible target for future treatments aimed at age-related obesity and metabolic disease.
The study, published in Science, focused on white adipose tissue, the body’s main fat-storage tissue. City of Hope said excess abdominal fat has been associated with slower metabolism, faster aging, type 2 diabetes, heart disease and other chronic conditions.
A change in fat-cell production
Scientists have known that existing fat cells can grow larger as people age, according to City of Hope. The research team examined whether aging also causes the body to make new fat cells at a higher rate.
The investigators studied adipocyte progenitor cells, or APCs, which are stem-like cells in fat tissue that can develop into mature fat cells. City of Hope said the work was done with UCLA collaborators and included mouse experiments followed by studies of human cells.
In one experiment, the team moved APCs from young and older mice into young mice. APCs taken from older animals produced many new fat cells, while APCs from young mice placed into older mice generated relatively few, according to the researchers.
City of Hope said that result suggested the fat-forming behavior was tied to the aged APCs themselves rather than to the age of the animal receiving the cells.
A newly identified cell type
The researchers used single-cell RNA sequencing to measure gene activity in individual cells. According to City of Hope, APCs were mostly inactive in young mice but became much more active in middle-aged mice.
The team reported that aging caused some APCs to shift into a newly identified cell population called committed preadipocytes, age-specific, or CP-As. City of Hope said these cells emerged with age and were especially capable of generating new fat cells.
The study also identified a signaling pathway involving leukemia inhibitory factor receptor, known as LIFR. According to City of Hope, LIFR helped CP-A cells multiply and mature into fat cells in older mice, while young mice did not need the same signal to make fat.
Qiong A. Wang, a City of Hope researcher and co-corresponding author of the study, said the findings indicate LIFR has an important role in prompting CP-As to produce new fat cells and expand belly fat in older mice. Adolfo Garcia-Ocana, another City of Hope researcher involved in the work, said the study provides evidence that age-related abdominal fat growth can come from increased output of new fat cells.
Human cell results
To test whether the mouse findings might be relevant to people, the researchers analyzed human tissue samples from people of different ages using single-cell RNA sequencing. City of Hope said the team found human cells that closely resembled CP-As.
Those CP-A-like cells appeared in higher numbers in tissue from middle-aged people and showed a strong ability to form new fat cells, according to the researchers. City of Hope said the result suggests a similar age-related process may occur in humans.
The researchers said more work is needed before the findings could lead to a therapy. City of Hope said future studies will track CP-A cells in animals, study how they behave in humans and test ways to block or remove them.
The study’s first authors were Guan Wang of City of Hope and Gaoyan Li of UCLA, according to the journal reference.
This story draws on original reporting from ScienceDaily.