Fig. 6: The UPR responsiveness is remodelled in aged worms extending lifespan upon HGD.

a Differentially expressed genes related to the UPR comparing each diet group with one another. b Overview of the unfolded protein response (UPR) in C. elegans. Created with BioRender.com. c qPCR comparing expression of genes cht-1, hsp-4, and F40F12.7 induced from UPR branches ATF-6, IRE-1, and PEK-1, respectively, in 1- and 5-day-old WT worms fed 24 h normal diet (ND, open circles) or high glucose diet (HGD, filled circles). Data shown are the mean ± SEM (n = 3). d–g Lifespan assay of 1- and 5-day-old atf-6(lof) (ND, n = 287; HGD-1, n = 99; HGD-5, n = 280 including biological replicates) (d) and pek-1(lof) (ND, n = 215; HGD-1, n = 52; HGD-5, n = 104 including biological replicates) (e) worm mutants fed ND or HGD. f Lifespan assay of ire-1(lof) worm mutant treated as in d (ND, n = 229; HGD-1, n = 387; HGD-5, n = 263 including biological replicates). Lifespan assays of WT, xbp-1(lof), gly-19p::xbp-1s, rab-3p::xbp-1s and jnk-1(lof) fed ND (g), HGD-1 (h) or HGD-5 (i). Statistical analysis was subjected to one-way ANOVA with Tukey’s test (c) or log-rank test for lifespan (d–i).