Figure 7. Schematic representation for the role of the ether lipid biosynthetic machinery in multiple pro-longevity paradigms.

(A) Model of ether lipid action in biguanide-prompted lifespan extension. Activation of ether lipid biosynthesis leads to longevity-promoting activity of metabolic stress defenses downstream of the transcription factor skn-1. (B) Model portraying a broader than previously appreciated role of ether lipids in longevity downstream of biguanides, mitochondrial electron transport inhibition, mTORC1 inhibition, and eat-2 mutation-mediated dietary restriction (EAT-2 DR). Dashed lines for DAF-16 indicate its requirement for fard-1 overexpression-, but not biguanide-mediated lifespan extension, suggesting a context-dependent role for daf-16/FoxO in mediating pro-longevity outcomes through modulation of ether lipid levels.