| Genetic Background | Lifespan Effect of PHB Depletion | UPRmt Response | Mechanism/Notes | Key Reference |
|---|---|---|---|---|
| Wild-type | Shortens lifespan (pqac-00000008, pqac-00000011, pqac-00000012, pqac-00000025) | Strongly induced (pqac-00000008, pqac-00000009, pqac-00000006) | PHB loss disrupts mitochondrial membrane organization and proteostasis, induces mitochondrial stress, and is generally detrimental in metabolically normal animals (pqac-00000001, pqac-00000016, pqac-00000018) | Gatsi et al. 2014; Fernández-Abascal et al. 2025; Lourenço & Artal-Sanz 2021 (pqac-00000008, pqac-00000012, pqac-00000025) |
| daf-2(e1370) | Extends lifespan (pqac-00000008, pqac-00000011, pqac-00000012, pqac-00000025) | Suppressed/attenuated relative to PHB-depleted wild type (pqac-00000008, pqac-00000009, pqac-00000025) | Canonical example of context dependence: defective IIS buffers some PHB-loss consequences; longevity links to altered lipid/energy metabolism and requires mitochondrial stress signaling components including ATFS-1 in recent work (pqac-00000008, pqac-00000010, pqac-00000011) | Gatsi et al. 2014; Fernández-Abascal et al. 2025; Lourenço & Artal-Sanz 2021 (pqac-00000008, pqac-00000010, pqac-00000025) |
| sgk-1(ok538) | Extends lifespan (reported ~18% in one study) (pqac-00000023, pqac-00000026, pqac-00000030) | Induced in sgk-1 mutants, but PHB depletion-associated longevity is accompanied by suppressed UPRmt relative to PHB-depleted wild type; later work also shows lifespan extension requires UPRmt and autophagy (pqac-00000025, pqac-00000027) | PHB depletion suppresses sgk-1 mitochondrial, lipogenesis, yolk/lipoprotein, ROS, and oxygen-consumption defects; indicates strong interaction with TORC2/SGK-1 and membrane-lipid homeostasis (pqac-00000023, pqac-00000027, pqac-00000029) | Gatsi et al. 2014; de la Cruz-Ruiz et al. 2021 (pqac-00000023, pqac-00000025, pqac-00000027) |
| rict-1(ft7) | Extends lifespan (pqac-00000025, pqac-00000030) | UPRmt regulation parallels sgk-1; rict-1 loss suppresses PHB depletion-associated UPRmt and interacts with SGK-1 in a pathway parallel to DAF-2 (pqac-00000024, pqac-00000025, pqac-00000030) | Supports model that mTORC2/RICT-1-SGK-1 signaling is a major determinant of whether PHB depletion is pro- or anti-longevity (pqac-00000024, pqac-00000028, pqac-00000030) | Gatsi et al. 2014 (pqac-00000024, pqac-00000025, pqac-00000030) |
| Dietary restricted animals | Extends lifespan (pqac-00000012) | Not specified directly in the cited review excerpt (pqac-00000012) | Lourenço & Artal-Sanz summarize that PHB depletion can extend lifespan in dietary restriction contexts, reinforcing that PHB effects depend on systemic metabolic state rather than PHB acting as a simple pro- or anti-aging factor (pqac-00000012, pqac-00000013) | Lourenço & Artal-Sanz 2021 (pqac-00000012, pqac-00000013) |


*Table: This table summarizes how prohibitin depletion has opposite effects on lifespan depending on the C. elegans genetic or metabolic background. It is useful for quickly comparing longevity outcomes, UPRmt behavior, and the major mechanistic interpretations across key studies.*