Restoring hypothalamic Menin in aged mice improved skin, bone, cognition and lifespan, while D‑serine supplementation boosted cognition alone.
Restoring the brain protein Menin in the hypothalamus of 20‑month‑old mice reversed several age‑related changes. Gene delivery of Menin increased skin thickness, bone mass, performance on learning, memory and balance tests, raised hippocampal D‑serine levels, and extended lifespan compared with untreated controls.
In younger mice, conditional knockout of Menin in ventromedial hypothalamic neurons caused hypothalamic inflammation and produced multiple aging phenotypes, including reduced bone density, thinner skin, cognitive decline and a modestly shorter lifespan. Menin loss also lowered D‑serine production by reducing activity of the enzyme that synthesises this amino‑acid neurotransmitter.
A separate experiment gave D‑serine in drinking water for three weeks, which improved cognitive performance in both young and old mice but did not reproduce the broader physical improvements seen after Menin restoration. Researchers noted that D‑serine supplementation is not equivalent to dietary L‑serine intake.
The study’s authors suggested that age‑related decline of hypothalamic Menin may drive systemic aging, but the relevance to humans remains uncertain and further research is needed to determine underlying mechanisms, durability of benefits, and safety of targeting Menin or D‑serine in people.