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Would love to see the full paper for more details on how, but apparently they determined cells' fighting ability is controlled by their choice of fuel source.

Active T cells prefer to process acetate (via ACSS2 enzyme), while exhausted T cells switch to using citrate (via ACLY enzyme). Appears this choice isn't just about energy - it actually determines cell fate by affecting where acetyl-CoA accumulates in the nucleus, which then controls which genes get turned on or off.

The breakthrough is likely that this appears to be an active choice by the cell, not just a response to what's available. Best case scenario, we might be able to prevent T cells from becoming exhausted in cancer treatment by controlling their metabolic preferences.

It's like active T cells drinking Gatorade (acetate) to stay energized, but when they get tired, they switch to lemon water (citrate), which isn’t as good for keeping them strong. By noticing this fuel switch, scientists can identify tired T cells and possibly find ways to get them back on Gatorade to keep fighting sickness.