Memory problems, thinning skin, and decreased bone mass may seem like independent consequences of aging. However, experiments in mice suggest that changes in a protein deep in the brain can influence all three. Restoring that protein, called Menin, improved several signs of aging, while a separate treatment with the amino acid D-serine improved cognition.
The findings come from a study published March 16, 2023 in the open access journal. More biologyled by Lige Leng of Xiamen University in Xiamen, China, and colleagues. The work identified a possible connection between brain inflammation, metabolism and aging throughout the body. Research published since then has contributed to that picture, while also showing why the supplement’s findings require careful interpretation.
How a brain protein could influence aging
The researchers focused on the hypothalamus, a small region of the brain that helps coordinate metabolism and other essential functions. It also appears to influence how the body ages. As inflammatory signaling in this region increases, it may contribute to changes both within the brain and in tissues elsewhere in the body.
Before the 2023 study, Leng and his colleagues had discovered that Menin helps curb inflammation in the hypothalamus. This raised an important question: Could losing some of this protection help kick-start age-related decline?
The team found that Menin levels decreased with age in certain neurons in the ventromedial hypothalamus, an area involved in regulating metabolism. The same decline was not seen in astrocytes and microglia, two types of cells that support and protect the brain. This suggested that the change was specific to particular cells rather than a uniform loss across the region.
To investigate whether the loss of Menin could actually contribute to aging, rather than simply accompany it, the researchers created conditional knockout mice. These animals were genetically modified so that Menin could be selectively eliminated. Depletion of Menin in younger mice increased hypothalamic inflammation and led to several aging-related traits, including lower bone mass, thinner skin, cognitive decline, and a modestly shorter lifespan.
The D-Serine Connection
The loss of menin also disrupted a chemical pathway important for communication between brain cells. Mice with less menin had lower levels of D-serine, an amino acid that helps activate receptors involved in learning and memory. These receptors help neurons adjust the strength of their connections, an essential process for storing information.
An enzyme involved in the production of D-serine (which in turn was regulated by Menin) became less active, reducing the supply of amino acids. The findings suggested that Menin could influence cognition not only through inflammation, but also by helping to maintain the chemistry that supports brain signaling.
D-serine is sometimes used as a dietary supplement, but an important distinction can be lost in discussions about food sources. Serine is found in foods such as soy, eggs, fish and nuts, while the form incorporated into dietary proteins is L-serine. The body can convert L-serine to D-serine, but the two forms are not interchangeable and eating these foods is not equivalent to receiving the experimental D-serine treatment.
Menin restoration in aged mice
Next, the researchers tested whether increasing Menin levels could improve the condition of aged (20-month-old) mice. They introduced the Menin gene into the hypothalamus, allowing cells in that region to produce more protein.
Thirty days later, the treated mice experienced improvements in skin thickness and bone mass, along with better performance on tests of learning, cognition and balance. The changes were accompanied by higher levels of D-serine in the hippocampus, a brain region essential for learning and memory. The study also reported that Menin restoration extended the lifespan of the treated mice.
A separate experiment tested a simpler approach: giving mice D-serine in their drinking water for three weeks. This improved cognitive performance, even in older animals. However, the supplement did not replicate the broader improvements in physical aging traits seen after Menin’s restoration. The distinction matters: The study did not show that taking D-serine reversed aging throughout the body.
At the time, Leng described the potential importance of the findings:
“We speculate that decreased 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: “Ventromedial hypothalamus (VMH) Menin signaling was decreased in aged mice, contributing 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
Subsequent studies have explored related mechanisms, although they should not be treated as direct confirmation of the entire Menin aging pathway.
A study published in the Journal of physiology and biochemistry in March 2024 examined Menin in cultures of mouse hippocampal cells exposed to the stress hormone corticosterone. A compound called itaconate increased Menin levels and reduced inflammation and a form of cell death. When investigators silenced Menin, that protection disappeared. The result supported a protective role for Menin in another experimental setting, but it was a cellular study, not a demonstration of slower aging in animals or people.
Other work has reinforced the argument that communication between the hypothalamus and the rest of the body can influence aging. In 2024 cellular metabolism In the study, researchers at the University of Washington School of Medicine identified a different group of hypothalamic neurons that communicates with adipose tissue. Interventions that maintained or stimulated this system increased physical activity and prolonged the lifespan of the mice. The study involved a different molecular pathway than Menin, but reinforced the broader idea that brain signals can affect aging beyond the brain.
A much broader view emerged in January 2025, when a team at the Allen Institute reported an analysis of approximately 1.2 million mouse brain cells in Nature. Some of the cell types most sensitive to aging were concentrated around the third ventricle of the hypothalamus, a fluid-filled cavity. Many showed reduced activity in genes associated with neuronal function along with increased activity in genes related to immune responses. That study mapped changes associated with aging rather than testing a treatment, but highlighted the hypothalamus as an important area for future research.
Why more D-serine is not necessarily better
Further research also complicates the idea that increased D-serine should always benefit an aging brain.
In April 2025, a study in Cellular and molecular life sciences examined mice engineered to develop characteristics of Alzheimer’s disease. In that model, an early increase in D-serine accompanied alterations in brain signaling. Genetic deletion of the enzyme that produces D-serine prevented or reduced several later cognitive problems. This was a different biological setting than Menin’s experiments, but he demonstrated that D-serine can have different effects depending on the underlying pathological process.
Research published on September 16, 2026 in the Alzheimer’s Disease Journal was pointing in another direction. In a different Alzheimer’s mouse model, an L-serine-enriched diet increased blood levels of L-serine and D-serine and partially restored measures of new neuron production in the hippocampus. It did not improve the buildup of amyloid, a protein associated with Alzheimer’s disease. Importantly, this experiment tested L-serine and the production of new neurons, not D-serine supplementation as a treatment for human aging.
Taken together, these findings suggest that serine metabolism is a promising research target, but not a simple case of more is better. The form of the serine, the condition being studied, and the outcome being measured are important. Neither study directly confirms or overturns Menin’s original results.
What the findings mean for people
There is some research in humans on D-serine, although it does not establish an anti-aging treatment. A small randomized study published in 2016, before Menin’s work, tested a single dose in 50 healthy older adults. Participants improved on one measure of a computerized maze task, but the researchers found no significant benefit on the other cognitive tests or measures of mood. The experiment did not establish lasting benefits for memory, slower aging, or the safety of long-term use in older adults.
Menin’s findings leave several important questions unresolved. Researchers still need to determine what causes the protein to decline with age, how much of the resulting physical and cognitive decline can be prevented, and how long the benefits might last. They also need to understand whether altering Menin or supplementing D-serine could produce unwanted effects.
The central possibility remains compelling: Some changes associated with aging may be influenced by signals originating in a small part of the brain. Understanding those signals could reveal ways to protect function later in life. For now, however, the evidence points to an experimental avenue worth investigating, not a supplement shown to slow human aging.