Scientists have found that restoring a protein in the brain can partially reverse several signs of aging in mice, while a separate treatment with the amino acid D-serine improved cognitive performance.

The findings suggest that changes in a protein called Menin, which is found in a small region of the brain, may play a role in age-related changes affecting memory, skin and bone health.

The study, led by Lige Leng of Xiamen University in China, was published in the open-access journal PLOS Biology in March 2023. It identified a possible link between brain inflammation, metabolism and aging throughout the body.

How Menin may affect aging
The researchers focused on the hypothalamus, a small region of the brain that helps regulate metabolism and other essential functions. The region also appears to play a role in how the body ages.

Earlier research by Leng and his colleagues found that Menin helps control inflammation in the hypothalamus. They then investigated whether a decline in the protein could contribute to age-related changes.

The researchers found that Menin levels declined with age in certain neurons in the ventromedial hypothalamus, a region involved in metabolism. The same decline was not observed in astrocytes and microglia, two types of cells that support and protect the brain.

To determine whether the loss of Menin contributed to aging, rather than simply occurring alongside it, the scientists created genetically modified mice in which the protein could be selectively removed.

Reducing Menin levels in younger mice increased inflammation in the hypothalamus and led to several aging-related changes, including reduced bone mass, thinner skin, cognitive decline and a slightly shorter lifespan.

Link to D-serine
The loss of Menin also affected a chemical pathway involved in communication between brain cells.

Mice with lower Menin levels had less D-serine, an amino acid that helps activate receptors involved in learning and memory. These receptors allow neurons to adjust the strength of their connections, a process important for storing information.

An enzyme involved in producing D-serine was also affected, reducing the supply of the amino acid.

The findings suggested that Menin could influence cognitive function through both inflammation and the chemical processes needed for communication between brain cells.

D-serine is sometimes sold as a dietary supplement, but researchers caution that it should not be confused with L-serine, the form of serine found in dietary proteins.

Foods such as soybeans, eggs, fish and nuts contain L-serine. The body can convert L-serine into D-serine, but the two forms are not interchangeable. Eating these foods is therefore not equivalent to receiving the experimental D-serine treatment used in the study.

Restoring Menin in older mice
The researchers then tested whether increasing Menin levels could improve the health of 20-month-old mice.

They introduced the Menin gene into the animals' hypothalamus, allowing cells in the region to produce more of the protein.

After 30 days, the treated mice showed improvements in skin thickness and bone mass. They also performed better in tests measuring learning, cognition and balance.

The treatment was accompanied by higher levels of D-serine in the hippocampus, a brain region important for learning and memory. The study also reported that restoring Menin extended the animals' lifespan.

In a separate experiment, researchers gave mice D-serine through their drinking water for three weeks. The treatment improved cognitive performance, including in older mice.

However, D-serine alone did not produce the broader physical improvements seen after Menin was restored. The study therefore did not show that D-serine supplementation could reverse aging throughout the body.

Leng said the decline of Menin in the hypothalamus could be one factor driving aging and that the protein may connect genetic, inflammatory and metabolic processes involved in aging.

Later research adds to the picture
Subsequent studies have examined related biological processes, although they do not directly confirm the entire Menin aging pathway.

A study published in the Journal of Physiology and Biochemistry in March 2024 examined Menin in cultured mouse hippocampal cells exposed to the stress hormone corticosterone. Researchers found that a compound called itaconate increased Menin levels and reduced inflammation and a form of cell death.

When Menin was silenced, those protective effects disappeared. However, because the work was conducted in cells rather than living animals, it did not show that the treatment could slow aging.

Another 2024 study published in Cell Metabolism found that a different group of hypothalamic neurons communicates with fat tissue. Researchers at Washington University School of Medicine reported that maintaining or stimulating this system increased physical activity and extended lifespan in mice.

The study involved a different biological pathway from Menin but provided further evidence that signals from the brain can affect aging elsewhere in the body.

In January 2025, researchers at the Allen Institute analyzed about 1.2 million mouse brain cells in a study published in Nature. They found that some of the brain cells most affected by aging were concentrated around the third ventricle of the hypothalamus.

Many of those cells showed lower activity in genes linked to neuron function and higher activity in genes associated with immune responses.

The study did not test a treatment but identified the hypothalamus as an important area for further aging research.

More D-serine may not always be better
Later research has also raised questions about whether increasing D-serine is always beneficial to the aging brain.

A study published in Cellular and Molecular Life Sciences in April 2025 examined mice with features of Alzheimer's disease. Researchers found that an early increase in D-serine was associated with changes in brain signaling.

When scientists genetically removed the enzyme responsible for producing D-serine, several later cognitive problems were prevented or reduced.

The study involved a different disease model from the Menin research, but it showed that D-serine can have different effects depending on the underlying condition.

Research published Sept. 16, 2026, in the Journal of Alzheimer's Disease found that feeding L-serine to mice in another Alzheimer's model increased blood levels of both L-serine and D-serine and partially restored the production of new neurons in the hippocampus.

However, the treatment did not reduce the buildup of amyloid, a protein associated with Alzheimer's disease.

That study examined L-serine and the production of new neurons, rather than D-serine supplementation as a treatment for human aging.

Together, the findings suggest that serine metabolism may be an important area of research, but increasing serine is not necessarily beneficial in every situation. The form of serine, the disease or condition being studied and the outcome being measured all matter.

What the findings mean for humans
Some research has examined D-serine in humans, but there is no evidence that it can be used as an anti-aging treatment.

A small randomized study published in 2016 involved 50 healthy older adults who received a single dose of D-serine. Participants performed better on one measure of a computerized maze task, but researchers found no significant improvement in other cognitive tests or measures of mood.

The study did not demonstrate lasting memory benefits, slower aging or the safety of long-term D-serine use in older adults.

The Menin research also leaves several questions unanswered. Scientists still need to determine why Menin levels decline with age, how much age-related physical and cognitive decline can be prevented by restoring the protein, and how long any benefits might last.

Researchers also need to determine whether changing Menin levels or taking D-serine could cause unintended effects.

The findings point to the possibility that some age-related changes may be influenced by signals originating in a small region of the brain. Understanding those signals could eventually help researchers find ways to preserve physical and cognitive function later in life.

For now, however, the evidence points to an experimental biological pathway that requires further study, rather than a proven supplement or treatment capable of reversing human aging.

Source: Science Daily