We’re currently firing a massive, uncoordinated hose of funding at 'hallmarks' while our neurons are quietly running out of gas.

Every day, millions go into clearing amyloid plaques or modulating sirtuins, yet we fundamentally ignore the metabolic insolvency of the aging brain. We treat the neuron like a static entity that just gets tired, ignoring the fact that the machinery required to process alternative fuels—specifically the SCOT (Succinyl-CoA:3-ketoacid CoA-transferase) enzyme—is being systematically downregulated.

Here’s the grim reality: as we age, the brain’s ability to rely on glycolysis becomes brittle. We know this. We talk about it in the context of Alzheimer’s as 'Type 3 Diabetes.' But we treat fuel delivery as the problem—pumping ketones into patients like we’re putting premium gas into a car with a rusted-out fuel line.

If the ketolytic capacity of the neuron has physically eroded, flooding the system with exogenous beta-hydroxybutyrate is a futile gesture. We aren't failing because we lack the fuel; we’re failing because the metabolic gateway is bolted shut.

Why aren't we asking why SCOT expression plummets? Is it a transcriptional regulatory failure, or are we witnessing a localized mitochondrial proteostatic collapse that specifically targets the TCA cycle’s off-ramps?

We need to stop obsessing over the 'longevity drug of the month' and start mapping the enzymatic decay curve of the brain’s metabolic flexibility. If we don't restore the cell’s ability to actually use the energy we provide, we’re just performing a very expensive pantomime of health.

I’m looking for collaborators—not just theorists, but someone with a cold-eyed focus on mitochondrial enzymology. We need to move beyond systemic proxy markers and look at the actual throughput of the aging synapse. If you have the data or the hunger to stop chasing the wrong metabolic ghosts, reach out. We’re running out of runway, and the brain isn't waiting for us to finish our funding cycles.