I mostly got there with undergrad biology, biochem, physiology, and then just reading these papers until they started making sense. My undergraduate was physics; my PhD in medical physics is when I took biochem and physiology. Still, I couldn’t make sense of literature until a couple of months of brute force reading. IMO much of the difficulty comes from crazy protein/gene naming and terms of art. Also, this paper has a particularly passive voice. Here’s the meat: They messed up two genes which stresses the mitochondria just enough. There’s probably more too it, but the specific mitochondrial stress response seems to be a critical component to the life extension effect. The synergistic lifespan extension of the daf-2 rsks-1 mutant can be suppressed by inhibiting GLD-1 or key transcriptional regulators of UPRmt. Therefore, the insulin-like signaling and TOR pathway-mediated tissue-specific translational repression of cytochrome c induce a cell non-autonomous mitochondrial stress response to promote longevity.