Two Brain Enzymes, Opposite Roles in Memory as Mice Age

Jeff's Daily Pick. Two enzymes that break down fats in the brain pull memory in opposite directions. In old mice, boosting one and silencing the other both improved memory.

In the United States and China, two studies published in October 2026 point to the same family of enzymes, phospholipases, as regulators of memory in the aging brain. Both include Amar Sahay, a neuroscientist at Massachusetts General Hospital and Harvard Medical School, among their authors. One enzyme appears to protect; the other appears to erode.

The protector: Pla2g2f

In Nature Neuroscience on October 15, a team led by Vicidomini and colleagues reported that the gene Pla2g2f became more active when connections between some neurons were disrupted in mice. Mice engineered to lack the gene showed a surge of inflammation and neuron degradation as they aged, and middle aged knockout mice scored lower on spatial memory tests than controls. Mice with extra Pla2g2f had less inflammation and better connected neurons, and older animals with boosted levels scored higher than older controls, Nature's news team reported. In human data, PLA2G2F activity rose with age, and in brains from donors who had been cognitively tested before death, it was highest in resilient people whose cognition stayed intact despite amyloid deposits. Sahay described the enzyme as a compensatory cognitive resilience mechanism.

The saboteur: PLA2G7

In Nature Aging, a team led by Fuling Wu, Yingxue Wu and Nannan Guo at Southern Medical University, with Sahay, reported that neural stem cells in the hippocampus secrete PLA2G7, which weakens inhibitory synapses in the dentate gyrus, the gateway region for new memories. When the researchers silenced the gene in aged mice, inhibitory synapses rebounded, the balance of excitation and inhibition partly normalized, and the animals performed markedly better on demanding spatial learning and memory tests.

Put side by side, the papers suggest that lipid processing near neurons is part of how the hippocampus copes with age, with enzymes that push in both directions. Timothy Hohman of Vanderbilt, who was not involved, called the Pla2g2f work a great example of using a model system to get at resilience mechanisms that are hard to study in humans. Drugs are not yet on the table for either target.