Aging unlocks these cells' power to evolve and spread
Somewhere in the quiet machinery of middle age, the body begins rewriting its own instructions — not through neglect or excess, but through the awakening of cells that were never meant to be so busy. Scientists at City of Hope have identified a previously unknown stem cell type, called CP-As, that emerges during aging and accelerates the production of new belly fat cells, even in people who haven't changed their habits. The discovery, validated in both mice and human tissue, points to a specific biological pathway — LIFR signaling — as a potential lever for future therapies. It is a reminder that the body ages not only by wearing down, but sometimes by turning certain processes up.
- Millions of people experience unexplained belly fat accumulation in middle age, and science has now found a cellular culprit hiding in plain sight within fat tissue itself.
- A newly identified stem cell population — CP-As — appears specifically during aging and produces new fat cells at a dramatically accelerated rate, a process distinct from simple fat-cell enlargement.
- Transplant experiments in mice revealed that the aggressive fat-making behavior lives inside the older cells themselves, not in the aging environment surrounding them.
- The LIFR signaling pathway emerged as the key biological switch older bodies use to activate CP-A cells, offering researchers a concrete target to potentially block or disrupt.
- Human tissue samples confirmed that CP-A-like cells appear in greater numbers in middle-aged individuals, suggesting the same mechanism operates across species.
- Clinical applications remain years away, but the research — published in Science — opens a credible new front in the effort to address age-related metabolic change at its source.
There is a particular frustration many people encounter in middle age: the body shifts, the waistline expands, and no obvious explanation accounts for it. Researchers at City of Hope have now uncovered a cellular mechanism that may explain this stubborn reality — a newly discovered stem cell type that awakens during aging and dramatically accelerates the creation of new fat cells, especially in the abdomen.
For years, scientists knew that fat cells enlarge with age, but suspected the body was also manufacturing new ones at an unusual rate. To investigate, the team studied adipocyte progenitor cells — stem cells within fat tissue capable of maturing into full fat cells. When they transplanted these cells from older mice into young ones, the older cells generated large numbers of new fat cells. The reverse experiment produced far fewer. The fat-making drive, it seemed, was encoded in the older cells themselves.
Using single-cell RNA sequencing, the researchers found that these stem cells were largely dormant in young mice but became highly active in middle age. More strikingly, some transformed into an entirely new cell population the team named CP-As — committed preadipocytes, age-specific. These cells proved especially efficient at producing fat and appeared to be central to the metabolic shift that defines middle age.
Tracing the signals behind this process, the team identified the LIFR pathway as a key driver — necessary in older mice but not in young ones. Blocking it could, in theory, prevent CP-As from emerging and slow belly fat accumulation. Human tissue analysis confirmed that similar cells appear in greater numbers in middle-aged people and carry the same fat-generating capacity.
The findings, published in Science, represent the first clear evidence that the expanding waistline of aging is driven by a surge in new fat cell production from these age-specific stem cells. Researchers now plan to track CP-A behavior in further animal and human studies, with the longer-term hope of developing therapies that address not just appearance, but the metabolic consequences that come with it.
There's a particular cruelty to aging that many people experience without fully understanding its mechanics: the slow accumulation of weight around the middle, even as the scale barely moves. You eat the same way you always have. You exercise. Yet the body changes. Scientists at City of Hope have now identified what may explain this stubborn biological reality—a newly discovered type of stem cell that awakens during middle age and dramatically accelerates the production of fresh fat cells, particularly in the abdominal region.
For decades, researchers understood that fat cells enlarge as people age, but they suspected something else was happening too: the body was manufacturing entirely new fat cells at an accelerated rate. To test this theory, the team conducted a series of experiments in mice, later validated by examining human tissue samples. They focused on adipocyte progenitor cells, or APCs—stem cells nestled within fat tissue that can mature into fully formed fat cells. When the researchers transplanted APCs from older mice into young mice, the results were striking. The older cells generated large numbers of new fat cells. The reverse experiment told a different story: APCs from young mice transplanted into older mice produced relatively few new fat cells. This suggested the aggressive fat-making capacity was intrinsic to the older cells themselves, not a product of the aging environment around them.
Using single-cell RNA sequencing to examine gene activity at the individual cell level, the researchers discovered that APCs were relatively dormant in young mice. But as mice reached middle age, these cells became highly active, churning out new fat cells at a much faster rate. More remarkably, some of these APCs transformed into an entirely new cell population that the team named committed preadipocytes, age-specific—or CP-As. These cells appeared specifically during aging and proved especially efficient at producing new fat cells. Their emergence may help explain the metabolic shift that occurs in middle age.
The researchers then traced the biological signals orchestrating this process. They identified a signaling pathway called leukemia inhibitory factor receptor, or LIFR, which appeared to play a central role in helping CP-A cells multiply and develop into fat cells. Young mice didn't require this signal to produce fat, but older mice did. This distinction suggested a potential therapeutic target: if scientists could block or eliminate LIFR signaling, they might be able to prevent the emergence of CP-As and slow belly fat accumulation.
To determine whether these findings extended beyond mice, the team analyzed human tissue samples from people of different ages using the same sequencing approach. They identified cells that closely resembled the newly discovered CP-As, and these cells appeared in greater numbers in tissue from middle-aged individuals. The human CP-As also demonstrated a strong capacity to generate new fat cells, suggesting that a similar biological process unfolds in people. Qiong Wang, the study's co-corresponding author and an associate professor at City of Hope's Arthur Riggs Diabetes & Metabolism Research Institute, noted that understanding how CP-As emerge during aging could lead to new medical solutions for reducing belly fat and improving health outcomes.
The discovery opens a new avenue for treating age-related obesity, though significant work remains. Researchers plan to track CP-A cells in animal studies, investigate their behavior in humans, and explore ways to block or eliminate them. If such approaches prove successful, they could potentially prevent the belly fat accumulation that commonly accompanies aging—addressing not just a cosmetic concern but a metabolic shift that affects health and longevity. The study's findings, published in the journal Science, represent the first clear evidence that the body's expanding waistline in older age is driven by the high output of new fat cells from these age-specific stem cells.
Notable Quotes
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.— Qiong Wang, City of Hope
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.— Adolfo Garcia-Ocana, City of Hope
The Hearth Conversation Another angle on the story
So we've known for a long time that people gain weight as they age. What's actually new here?
The new part is understanding *how* it happens at the cellular level. Scientists thought fat cells just got bigger. But this research shows the body is actually manufacturing new fat cells at a much faster rate in middle age—and they've identified the specific stem cells responsible.
And these stem cells—the CP-As—they only show up when you get older?
That's the striking part. They emerge during middle age specifically. It's not that older people have more of the same stem cells they always had. The aging process itself triggers the creation of an entirely new type of stem cell that's exceptionally good at making fat.
If we could block these cells, would that stop belly fat from accumulating?
In theory, yes. But we're still in the early stages. They've identified the signaling pathway—LIFR—that controls these cells. The next step is figuring out how to safely interrupt that signal without disrupting other important processes.
Does this apply to humans, or is it just a mouse thing?
They found similar cells in human tissue samples, and they behaved the same way. But there's a big difference between finding something in a tissue sample and proving it works as a treatment in living people. That's years away.
What does this mean for someone who's already gained belly fat?
That's the honest answer we don't have yet. This research explains why it happens. Whether you can reverse it by targeting these cells is a separate question that still needs to be answered.