Restoring Menin in old mice improved skin, bone and cognition within 30 days

The strength of the design is that Menin was tested in both directions. Falling levels on their own show an association, and they showed up in certain ventromedial hypothalamus neurons while astrocytes and microglia in the same region kept theirs ^[3][4]. So the team built conditional knockout mice and switched the protein off on purpose ^[5]. Young animals without it developed hypothalamic inflammation, lower bone mass, thinner skin, cognitive decline and a modestly shorter lifespan, and they were not yet old when those traits appeared ^[6]. Leng's group had previously found that Menin restrains inflammation in the hypothalamus ^[7], a region that coordinates metabolism and whose inflammatory signalling reaches tissues elsewhere in the body ^[17].

The reversal arm went into 20-month-old mice, with the gene for Menin delivered to the hypothalamus ^[10]. Thirty days is about 5 percent of the age of a 20-month-old mouse ^[20]. Within that window the treated animals had thicker skin, greater bone mass and better performance on tests of learning, cognition and balance ^[11].

A second route out of the hypothalamus runs through D-serine. Mice with less Menin made less D-serine, because an enzyme in the production pathway, itself regulated by Menin, lost activity ^[8]. D-serine activates receptors that neurons use to adjust the strength of their connections when they store information ^[9]. The gene went into the hypothalamus, and the D-serine rose in the hippocampus ^[12].

Giving D-serine on its own also improved cognition in these mice ^[13]. Food does not substitute for that. The serine in soybeans, eggs, fish and nuts is L-serine, the body converts some L-serine into D-serine, and the two forms are not interchangeable ^[15].

The paper appeared on 16 March 2023 and the account that surfaced it on 18 September 2026, about three and a half years later ^[1][2][19]. That account does not state sample sizes or effect sizes, so a reader cannot tell from it how large any of these improvements were ^[18]. Whether restoring Menin lengthens life is untested here; the knockout shortened lifespan modestly ^[6], and the gains reported in the old animals were skin, bone, behaviour and hippocampal D-serine ^[11][12]. In my view the cognition arm is the only part of this with a small-molecule handle so far, and it needs a second species before it needs a dose.