A team of researchers has put back a human brain protein known as Menin into laboratory mice, and they say doing so turned back several markers of aging. Their work, reported in the journal PLOS Biology, shows that restoring the protein brought back bone mass, thicker skin, and better memory and thinking ability. The study was led by Lige Leng of Xiamen University in Xiamen, China, and his group.
Scientists have found evidence suggesting that brain swelling, bodily metabolism, and aging may be connected. The study also makes clear the need for thorough testing of supplements before any claim is made that they can undo the aging process.
How a Brain Protein Influences Aging
This tiny part of the brain manages how the body uses energy and regulates other critical processes. It may also influence how the body ages. When inflammatory signals increase there, they can prompt shifts inside the brain itself as well as in tissues throughout the rest of the body.
Prior to the 2023 report, Leng and her team discovered that Menin assists in controlling inflammation within the hypothalamus. This prompted researchers to wonder whether reducing that safeguard might contribute to the onset of age-related decline.
Levels of Menin dropped with age in certain neurons within the ventromedial hypothalamus, a region tied to metabolism regulation. Astrocytes and microglia, cell types that support and shield the brain, did not show the same decline. That contrast pointed to a selective change confined to particular cells rather than a general loss throughout the region.
The scientists wanted to see if taking away Menin might cause aging, so they made mice that could have their Menin removed at will. These animals had been changed in such a way that Menin could be taken out from them. When Menin was reduced in young mice, it caused inflammation in the brain region tied to aging, along with several traits linked to getting older: less bone mass, thinner skin, a drop in mental ability, and a life span shortened by a small amount.
The D-Serine Connection
The absence of Menin also interfered with a chemical pathway vital to communication between nerve cells. In mice with reduced amounts of Menin, there were lower levels of D-serine, an amino acid that assists in activating receptors tied to learning and memory. Those receptors aid neurons in adjusting the strength of their connections, which is necessary for holding onto information.
The activity of an enzyme tied to D-serine production fell, cutting the supply of that amino acid. This led researchers to conclude that Menin might shape cognition through more than just inflammation; it could also help keep the chemical balance that supports brain signaling intact.
Serine shows up naturally in foods including soybeans, eggs, fish, and nuts, though it comes in the form known as L-serine. Dietary supplements sometimes use D-serine, but the two forms of serine are not interchangeable. The body can change L-serine into D-serine, but consuming those foods does not deliver the same thing as receiving the experimental D-serine treatment.
Restoring Menin in Older Mice
Next, the scientists examined whether increasing Menin levels would benefit older (20-month-old) mice. To do so, they inserted the gene for Menin into the hypothalamus, which caused cells there to make more of the protein.
Thirty days after treatment, the animals showed gains in both skin thickness and bone mass, alongside stronger results on tests of learning, cognition, and balance. These changes came with elevated D-serine levels in the hippocampus, which plays a central role in learning and memory. The research also found that restoring Menin lengthened lifespan in the treated group.
Researchers ran a separate trial where mice drank water laced with D-serine over three weeks. That regimen boosted cognitive performance, even among older animals. Still, the supplement failed to match the wider gains in physical aging traits brought on by Menin restoration. The difference is key: the study did not demonstrate that consuming D-serine turned back aging across the whole body.
At the time, Leng described the potential significance of the findings:
“We speculate that the decline of Menin expression in the hypothalamus with age may be one of the driving factors of aging, and Menin may be the key protein connecting the genetic, inflammatory, and metabolic factors of aging. D-serine is a potentially promising therapeutic for cognitive decline.”
Leng added the remark, “Ventromedial hypothalamus (VMH) Menin signaling diminished in aged mice, which contributes to systemic aging phenotypes and cognitive deficits. The effects of Menin on aging are mediated by neuroinflammatory changes and metabolic pathway signaling, accompanied by serine deficiency in VMH, while restoration of Menin in VMH reversed aging-related phenotypes.”
What Later Research Has Added
Later research has investigated similar mechanisms, though it should not be taken as direct confirmation of the whole Menin aging pathway. One study appeared in the Journal of Physiology and Biochemistry in March 2024, looking at Menin in cultured mouse hippocampal cells.
| Treatment | Target | Outcome |
|---|---|---|
| Menin gene delivery | Hypothalamus | Skin thickness, bone mass, cognition, lifespan |
| D-serine in water | Drinking water | Cognitive performance |
The Promise of Menin Restoration
Research into healthy aging has found a promising target. Mice regained several aspects of youth after a single brain protein was restored, including bone mass, skin thickness, and cognitive function. The link to D-serine points toward preserving normal brain signaling chemistry as a way to guard against age-related decline.
The findings do not point to supplements as a solution. When mice were given D-serine, cognition improved, yet the broader gains observed following Menin restoration were not reproduced. This shows that taking a pill cannot stand in for fixing the underlying biology.
This research underscores the need for cautious interpretation. Supplements are frequently promoted as cures for aging, yet the evidence supporting those claims usually falls short of the hype. The study demonstrates the reason: a therapy that boosts one characteristic can leave other traits untouched.
A small region of the brain that controls metabolism appears to serve as a control point for aging across the entire body. Experiments in mice show that memory problems, thinning skin, and declining bone mass — conditions that might otherwise seem unrelated — actually share a common origin in the ventromedial hypothalamus.
Before applying these results to people, the pathway’s existence must be confirmed in human studies. The findings so far show real promise.
Source material: “Scientists restore a brain protein and reverse signs of aging in mice,” ScienceDaily.
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