The findings come from a study published in PLOS Biology on March 16, 2023, by Lige Leng and colleagues at Xiamen University in Xiamen, China. The research identified a possible connection between brain inflammation, metabolism, and aging throughout the body. Studies published since then have added to the picture while also showing why the findings about D-serine require careful interpretation.

How menin in the brain may influence aging

The researchers focused on the hypothalamus, a small brain region that helps regulate metabolism and other essential functions. The hypothalamus also appears to influence how the body ages. Increased inflammatory signaling in this region can produce changes in the brain and in tissues elsewhere in the body.

Before the 2023 study, Leng and colleagues had discovered that menin helps suppress inflammation in the hypothalamus. This raised an important question: Could the loss of this protection contribute to progressive age-related decline?

The researchers found that menin levels declined with age in certain neurons in the ventromedial hypothalamus, a region involved in regulating metabolism. Similar reductions were not observed in astrocytes and microglia, which support and protect the brain. This suggests that the change may be specific to certain cell types rather than a uniform loss throughout the region.

To determine whether reduced menin contributes to aging rather than simply occurring alongside it, the researchers created conditional knockout mice. These animals were genetically engineered to selectively remove menin. Reducing menin in young mice increased inflammation in the hypothalamus and led to several aging-related traits, including reduced bone mass, thinner skin, impaired cognition, and a slightly shorter lifespan.

The connection between menin and D-serine

Loss of menin also disrupted chemical pathways 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 help neurons regulate the strength of their connections, a process essential for storing information.

The activity of enzymes involved in producing D-serine, which are controlled by menin, also decreased. This reduced the supply of the amino acid. The findings suggested that menin may affect cognition not only by regulating inflammation, but also by helping maintain chemicals needed for healthy brain signaling.

D-serine is sometimes used as a dietary supplement, but an important distinction can be overlooked when discussing food sources. Serine is found in foods such as soybeans, eggs, fish, and nuts, but the form incorporated into dietary proteins is L-serine. Although the body can convert L-serine into D-serine, the two forms are not interchangeable. Eating these foods is not equivalent to receiving experimental D-serine treatment.

What happened when researchers restored menin in old mice?

The researchers next tested whether increasing menin levels could improve signs of aging in 20-month-old mice. They delivered the menin gene to the hypothalamus, allowing cells in that region to produce more of the protein.

After 30 days, the treated mice had thicker skin, greater bone mass, and better performance on tests of learning, cognition, and balance. The treatment was also accompanied by increased D-serine levels in the hippocampus, a brain region essential for learning and memory. The study reported that restoring menin also increased the lifespan of the treated mice.

In a separate experiment, the researchers gave mice D-serine in their drinking water for three weeks. This improved cognitive ability, including in older animals. However, D-serine supplementation did not reproduce the broad improvements in physical aging seen after menin was restored. The study therefore did not show that taking D-serine reverses aging throughout the body.

At the time, Leng explained the potential significance of the findings:

“We speculate that the age-related decrease in menin expression in the hypothalamus may be one of the drivers of aging, and that menin may be an important protein that connects genetic, inflammatory, and metabolic factors of aging. D-serine may be a therapeutic agent for cognitive decline.”

Dr. Leng further stated:

“In aged mice, ventromedial hypothalamic (VMH) menin signaling is reduced, contributing to the systemic aging phenotype and cognitive impairment. The effects of menin on aging are mediated by neuroinflammatory changes and metabolic pathway signaling with serine deficiency in the VMH, but restoration of menin in the VMH reversed aging-associated phenotypes.”

What later research has added

Subsequent studies have investigated related mechanisms, but they should not be treated as direct confirmation of the entire menin-related aging pathway.

Research published in the Journal of Physiology and Biochemistry in March 2024 examined menin in cultured mouse hippocampal cells exposed to the stress hormone corticosterone. A compound called itaconic acid increased menin levels while reducing inflammation and a type of cell death. When researchers silenced the Menin gene, that protection disappeared. The results supported a protective role for menin in another experimental setting, but the study was conducted in cells and did not demonstrate slower aging in animals or humans.

Other research has strengthened the broader idea that communication between the hypothalamus and other parts of the body can influence aging. In a 2024 study published in Cell Metabolism, researchers at the University of Washington School of Medicine identified a distinct group of hypothalamic neurons that communicate with adipose tissue. Interventions that maintained or stimulated this system increased physical activity and extended lifespan in mice. Although this study involved a different molecular pathway from menin, it supports the possibility that signals from the brain can influence aging beyond the brain itself.

A larger picture 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, a fluid-filled cavity in the hypothalamus. Many showed reduced activity of genes associated with neurological function and increased activity of genes associated with immune responses. The study mapped age-related changes rather than testing treatments, but it highlighted the hypothalamus as an important area for further research.

Why more D-serine may not always be better

Later research has complicated the idea that increasing D-serine should always benefit the aging brain.

In an April 2025 study published in Cell and Molecular Life Sciences, researchers studied mice engineered to display features of Alzheimer’s disease. In that model, early increases in D-serine were accompanied by disruptions in brain signaling. Genetically removing the enzyme that produces D-serine prevented or reduced some later cognitive problems. Although this was a different biological setting from the menin experiment, it demonstrated that D-serine can have different effects depending on the underlying disease process.

On September 16, 2026, the Journal of Alzheimer’s Disease reported findings pointing in another direction. In a different Alzheimer’s disease mouse model, an L-serine-enriched diet increased blood levels of both L-serine and D-serine and partially restored measurements of new neuron production in the hippocampus. The accumulation of amyloid, a protein associated with Alzheimer’s disease, did not improve. 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 serine, the condition being studied, and the outcome being measured all matter. Neither study directly confirms or overturns the original findings about menin.

What the menin and D-serine findings mean for people

Some human studies of D-serine have been conducted, but no cure for aging has been established. Before the menin study, a small randomized study published in 2016 tested a single dose of D-serine in 50 healthy older adults. Participants improved on one measure of a computer maze task, but researchers found no significant effects on other cognitive tests or measures of mood. The experiment did not establish lasting improvements in memory, delayed aging, or the long-term safety of D-serine use in older adults.

The menin findings also leave several important questions unanswered. Researchers still need to determine what causes age-related loss of the protein, how effectively the resulting physical and cognitive decline can be prevented, and how long any benefits might last. They also need to understand whether changing menin levels or supplementing with D-serine could produce unintended effects.

Bottom line

The possibility that signals from a small region of the brain can influence multiple aspects of aging is compelling. Understanding those signals could eventually reveal ways to protect physical and cognitive function. For now, however, the evidence points to an experimental pathway worthy of further study—not to a supplement or treatment proven to reverse aging in humans.