HSP-1/HSPA8 directs selective translation towards longevity or immunity

Greer and colleagues describe HSP-1 in C. elegans and its human orthologue HSPA8 as a translation-control node that can shift cells toward longevity or immunity. HSP-1 depletion accelerated aging, removed the lifespan benefit associated with reduced translation, impaired lysosomal acidification and autophagy, and activated p38-MAPK immune signalling. HSPA8 depletion in human cells produced related changes in p38 signalling and lysosomal biology. The proposed model is that translation reduction is not a single beneficial switch. It changes the allocation of cellular resources, and HSP-1 helps determine whether the result supports maintenance or immune activation. This could help explain why broad translation or mTOR interventions have context-dependent effects. The evidence is mechanistic and preclinical. The abstract does not provide a human intervention, a validated aging biomarker endpoint or a dose that can be used clinically. HSPA8 is a core chaperone, so direct inhibition would carry substantial biological risk. The paper is useful for mechanism mapping but does not support a supplement, drug or evidence-grade change.

HSP-1/HSPA8 directs selective translation towards longevity or immunity.