Weight gain as we age is so common worldwide it’s almost a cliché. By age 50, the average person has gained about 15 pounds.
A recent study from Nagoya and Osaka Universities in Japan sheds light on why we tend to gain weight as we get older. The team says significant changes in the shape of neurons in the brain region that controls appetite and metabolism may be a key factor.
Age-related weight gain raises health risks from type 2 diabetes to heart disease, ScienceAlert reports.
While poor diet and a sedentary lifestyle certainly play a major role in midlife weight gain, scientists also warn that losing weight becomes significantly more challenging as we age.
How the Study Was Conducted
The team focused on the neurons in a part of the brain known as the hypothalamus, as well as a protein called the melanocortin-4 receptor (MC4R). This receptor helps regulate appetite and metabolism by balancing energy expenditure and intake. The researchers were curious: what if the cellular dynamics of this receptor correlate with metabolic changes, particularly age-related weight gain?
The team tested their hypothesis on laboratory rats. They used antibodies to tag MC4R proteins. The scientists identified tiny projections—primary cilia—on certain hypothalamic cells that contained MC4R.
Then came the most intriguing part. The researchers compared the levels of MC4R in the brains of young and adult rats and found differences in the shape of hypothalamic neurons, particularly in the length of the cilia. As the rats aged, these projections gradually shortened and virtually disappeared in many older and heavier rodents.
To determine the relationship between the disappearing cilia and diet, the team raised the test rats on different types of food. The rodents that consumed higher amounts of fat experienced a faster reduction in the length of their hypothalamic neuron cilia compared to those that ate a low-fat diet.
In the next phase of the study, the scientists turned to genetic engineering and artificially reduced the length of the cilia in the hypothalamus of young rats. As a result, these rodents ate more and burned less fat, leading to an increase in their body weight.
This weight gain occurred even after injections of the hormone leptin, which suppresses appetite. Thus, MC4R emerged as a critical link in the chain of appetite control.
What the Team Reported
Manami Oya said leptin resistance—when the body stops responding to the appetite-suppressing hormone leptin—is common in people with excess weight and makes treating obesity harder. Until now, the cause of age-related weight gain remained unclear, she added.
The research showed that in individuals aged 40 to 50, the shape of hypothalamic neurons changes—their cilia significantly shorten, while MC4R levels steadily decline. As a result, people gain weight. The team said a preference for fatty foods can lead to rapid weight gain in midlife and make that weight hard to lose.
Conversely, moderate eating can delay cilia shortening and preserve MC4R for longer. A proper diet helps the brain resist obesity into middle age, senior author Kazuhiro Nakamura said.
The results of the study were published in the journal Cell Metabolism.
