Researchers led by Lige Leng of Xiamen University reported that a protein called Menin, which helps restrain inflammation in a small region of the brain called the hypothalamus, gradually declines in certain neurons as mice age. Their findings, first published in March 2023 in PLOS Biology, tie that decline to several hallmarks of aging in mice, including more inflammation in the hypothalamus, thinner skin, reduced bone mass, worsening cognitive performance and a modestly shorter lifespan.
The more striking part of the work came when the team tried to reverse the damage. Using a gene delivery technique to boost Menin in the ventromedial hypothalamus of 20-month-old mice, they saw thicker skin, increased bone mass, better performance on tests of learning, memory and balance, and lower inflammation. Mice given the Menin treatment also lived longer than untreated controls in a separate survival analysis.
Menin turned out to influence a chemical signal as well. When Menin levels dropped, so did D-serine, an amino acid that helps regulate NMDA receptors involved in communication between neurons and in forming memories. Menin helps control PHGDH, an enzyme in the pathway that generates serine, so less Menin meant less D-serine reaching the brain. Restoring Menin raised D-serine in the hippocampus, a region central to learning and memory, and giving older mice D-serine in their drinking water for three weeks improved cognition. It did not restore the losses in bone mass or skin thickness, which suggests D-serine accounts for only part of what Menin does.
Work published since then points the same way: the hypothalamus appears to coordinate aging across the body. A 2024 Cell Metabolism study from Washington University School of Medicine described a different hypothalamic circuit linked to fat tissue that extended lifespan in mice, and a January 2025 Nature analysis of about 1.2 million mouse brain cells found that some of the most aging-sensitive cells sit around the third ventricle. Neither study tested the Menin pathway directly.
The D-serine part deserves caution. A 2016 randomized trial in 50 healthy older adults found improvement on only one spatial learning and problem-solving test, with no significant gains on the other cognitive or mood measures. An April 2025 Alzheimer's mouse study found that an early rise in D-serine accompanied brain signaling problems, so the amino acid's effects appear to depend on the condition, timing and context. High doses have also raised kidney safety concerns in animal experiments, and long-term safety in people is unknown. The source describes D-serine as an experimental approach rather than a proven treatment for brain aging.