Lifespan extension from missing mitochondrial proteins in C. elegans may not be due to protein protection responses

Knockdown of the genes mfn-1, cco-1, or nuo-6 resulted in increased longevity in Caenorhabditis elegans.

• Activation of the mitochondrial unfolded protein response (UPR(mt)) was associated with both increased and decreased longevity depending on the gene affected.
• Blocking the UPR(mt) pathway did not prevent lifespan extension from mfn-1, cco-1, or nuo-6 gene knockdown.
• UPR(mt) activation alone did not lead to increased longevity.
• Longevity increases from mfn-1, cco-1, or nuo-6 knockdown occurred independently of the GCN-2 nutrient-sensing pathway.
• The findings suggest that UPR(mt) and GCN-2 pathways are not responsible for lifespan extension associated with mitochondrial dysfunction.

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