Summary: New research uncovers that aging activates a
new type of stem cell that rapidly produces fat cells, explaining why
belly fat often expands in middle age. Scientists found that aging
triggers adipocyte progenitor cells (APCs) to evolve into committed
preadipocytes, age-specific (CP-As), which actively generate new fat.
A
signaling pathway called LIFR was found to drive this fat-cell
proliferation. These findings could lead to future therapies targeting
CP-As to prevent age-related fat gain and metabolic diseases.
Key Facts:
- New Fat-Making Cells: Aging triggers the emergence of CP-A cells that produce abundant new fat cells.
- Critical Pathway Identified: The LIFR signaling pathway fuels fat cell formation specifically in middle age.
- Potential Therapy Target: Blocking CP-As could help reduce age-related belly fat and extend healthspan.
Source: City of Hope
It’s no secret
that our waistlines often expand in middle-age, but the problem isn’t
strictly cosmetic. 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.
Now
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, has uncovered the cellular culprit behind
age-related abdominal fat, providing new insights into why our
midsections widen with middle age.
Credit: Neuroscience News
Published today in Science, the findings suggest a novel target for future therapies to prevent belly flab and extend our healthy lifespans.
“People
often lose muscle and gain body fat as they age—even when their body
weight remains the same,” said Qiong (Annabel) Wang, Ph.D., 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, one of the world’s foremost scientific
organizations dedicated to investigating the biology and treatment of
diabetes.
“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-corresponding author Xia Yang, Ph.D., 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.
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.
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 City of Hope
team 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.
“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,” said 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.
“This is the first evidence that our bellies expand with age due to the APCs’ high output of new fat cells.”
Aging
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.
“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,” explained 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.”
Using
single-cell RNA sequencing on samples from people of various ages, Wang
and her colleagues next studied APCs from human tissue in the lab.
Again,
the team also identified similar CP-A cells that had an increased
number in middle-aged people’s tissue. Their discovery also illustrates
that CP-As in humans have high capacity in creating new fat cells.
“Our findings highlight the importance of controlling new fat-cell formation to address age-related obesity,” said Wang.
“Understanding
the role of CP-As in metabolic disorders and how these cells emerge
during aging could lead to new medical solutions for reducing belly fat
and improving health and longevity.”
Future
research will focus on tracking CP-A cells in animal models, observing
CP-A cells in humans and developing new strategies that eliminate or
block the cells to prevent age-related fat gain.
The study’s first authors are City of Hope’s Guan Wang, Ph.D., and UCLA’s Gaoyan Li, Ph.D.
About this weight gain and aging research news
Author: Letisia Marquez
Source: City of Hope
Contact: Letisia Marquez – City of Hope
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Distinct adipose progenitor cells emerging with age drive active adipogenesis” by Qiong A. Wang et al. Science
