The forties often come with their share of physical changes: gray hair, baldness for some, the beginning of a loss of muscle mass, and a noticeable enlargement of the lower abdomen. This forty-year-old belly, more visible in men, is a source of stress and guilt. It's because we're not exercising enough, or because we're eating too much, or because we're not sleeping enough...
However, these behavioral changes are not the main causes. According to a study published on April 25, 2025 in the journal Science According to researchers at the City of Hope Medical Center in California, the determining factor is a completely natural proliferation of new fat cells (also called adipocytes) in the abdomen.
A metabolic shift in midlife
The authors studied this phenomenon in mice, tracking the appearance of new adipocytes. To do this, they transplanted adipocyte progenitor cells (stem cells that have the ability to become adipocytes) into young, healthy mice. They observed that the rate of differentiation of these cells into mature adipocytes was quite low in young adults. But at the midpoint of their lives (at 12 months), the mice began to produce many more new adipocytes, even though they continued to eat the same food as before.
“While most adult stem cells lose their ability to proliferate with age, the opposite happens with these stem cells.adipocyte progenitor cells: the sge unleashes their power of proliferation, summarizes Adolfo Garcia-Ocana, author of the study, in a press release. This shows for the first time that our bellies get bigger with age because of this high level of new fat cell production.”
This enlargement of adipose tissue led to weight gain, but also to physiological changes showing a metabolic shift: the body expended less energy and became less sensitive to insulin (a factor which increases the risk of type 2 diabetes).
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This shift is programmed by age
To confirm whether this phenomenon was indeed age-related, the researchers transplanted adipocyte progenitor cells from young mice into older mice, and vice versa. The younger mice that received cells from older mice also began to grow belly fat, showing that these cells were programmed to proliferate. Young cells in older mice, however, did not have the same effect because they were not yet programmed to proliferate. This programming is therefore indeed age-related, and would occur in midlife.
Cells that flourish around forty
Looking more closely, the authors noticed that only a specific group of adipocyte progenitor cells was affected by this age-related surge. These cells accumulated from the ninth month of age in the mice, peaking at 12 months, and then rapidly declining after 18 months (i.e., in the “senior” mice). These age-related cells were also visible in human samples, and again followed the same dynamics: very few in number in early adulthood, a rapid accumulation around forty, and a decline in old age.
“People tend to lose muscle mass and gain fat as they age, even when their body weight remains stable. This may be due to the arrival of a new type of stem cell that increases the body's ability to produce new fat cells, particularly around the belly,” explains Qiong (Annabel) Wang, co-author of the study.
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It might be possible to avoid the appearance of the forty-year-old belly
These age-related stem cells were identifiable by a specific marker, a receptor called LIFR (for "Leukemia inhibitory factor receptor"). And not only did they all have this receptor, but their activity depended on it. Thus, blocking LIFR, using drugs or genetically manipulating the mice, also blocked the proliferation capacity of these cells, without affecting other adipocyte progenitor cells. It would therefore be possible to take medical action to prevent them from making us grow a belly! The next step will therefore be to look for safe methods to block LIFR in humans, with the hope not only of refining our silhouettes, but above all of avoiding the accumulation of abdominal fat, a risk factor for a large number of diseases.
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