Gene rps-16 aco-2 rps-15 atp-2 C34B2.6 his-37 F23B12.5 F01G4.6 inf-1 F56D2.1 rpl-8 rps-5 pyc-1 mdh-1 eft-3 rps-0 eft-2 tbb-2 rpa-0 rpl-23 rps-20 rpl-31 F09F7.4 rpl-10a ZK829.4 rps-14 cpn-3 B0250.5 rrt-1 rpl-10 rpl-7 cct-1 rpl-17 acs-4 rps-11 rpl-3 rps-23 rack-1 pab-1 cct-8 sca-1 ORF T01C3.6 F54H12.1 F36A2.6 C34E10.6 C34B2.6 C50F4.7 F23B12.5 F01G4.6 F57B9.6 F56D2.1 Y24D9A.4 T05E11.1 D2023.2 F20H11.3 F31E3.5 B0393.1 F25H5.4 C36E8.5 F25H2.10 B0336.10 Y105E8A.16 W09C5.6 F09F7.4 Y71F9AL.13 ZK829.4 F37C12.9 F28H1.2 B0250.5 F26F4.10 F10B5.1 F53G12.10 T05C12.7 Y48G8AL.8 F37C12.7 F40F11.1 F13B10.2 F28D1.7 K04D7.1 Y106G6H.2 Y55F3AR.3 K11D9.2 Q22054 P34455 Q9XVP0 P46561 O44952 Q19749 Q0PDK0 P27639 P98080 Q9XVF7 P49041 O17732 O02640 P53013 P46769 P29691 P52275 Q93572 P48158 Q8WQA8 Q9U332 Q19278 Q9N4I4 Q23621 P48150 O01542 Q9XTI0 Q19825 Q09533 O01802 P41988 Q9BL19 Q20121 Q20206 Q6BEU5 Q19877 Q21215 Q9U302 Q9N358 Q9XU13 Protein of the small ribosomal subunit Probable mitochondrial aconitase Protein of the small ribosomal subunit Mitochondrial membrane ATP synthase Mitochondrial Lon protease ortholog H4 histone Component of mitochondrial pyruvate dehydrogenase Probable mitochondrial phosphate carrier protein Eukaryotic initiation factor 4A Mitochondrial cytochrome b-c1 subunit Protein of the large ribosomal subunit Protein of the small ribosomal subunit Pyruvate carboxylase-1 Malate dehydrogenase-1 Elongation factor 1-alpha Protein of the small ribosomal subunit Elongation factor 2 Beta tubulin ortholog Protein of the large ribosomal subunit Protein of the large ribosomal subunit Protein of the small ribosomal subunit Protein of the large ribosomal subunit Probable Enoyl-CoA hydratase Protein of the large ribosomal subunit Probable glutamate dehydrogenase Protein of the small ribosomal subunit Calponin ortholog Probable mitochondrial 3-hydroxyisobutyrate dehydrogenase Probable arginyl-tRNA synthetase Protein of the large ribosomal subunit Protein of the large ribosomal subunit Alpha subunit of cytosolic chaperonin complex Protein of the large ribosomal subunit Probable fatty acid Co-A synthetase Protein of the small ribosomal subunit Protein of the large ribosomal subunit Protein of the small ribosomal subunit Probable guanine nucleotide binding protein subunit beta-2-like 1 Ortholog of receptor activated c kinase Theta subunit of cytosolic chaperonin complex Sarco-endoplasmic reticulum Ca2+ ATPase 8.3 20.5 9.7 14.8 10.8 4.5 9.9 11.9 21.4 14.1 12.3 4.0 4.9 4.1 18.1 15.1 7.1 5.1 6.6 17.7 23.6 15.5 10.7 23.2 11.1 6.4 9.9 10.2 26.6 20.4 9.5 10.1 13.2 6.1 29.8 28.6 22.7 9.8 24.0 16.0 18.6 124 Aging, protein solubility and lifespan in C. elegans, P. Reis-Rodrigues et al. Table 1 Summary of survival analysis knocking down transcripts encoding insoluble proteins Accession number* Description Mean extension (%)† Lifespan experiments were repeated three independent times. Lifespan extension upon RNAi treatment was considered when a signiﬁcant (P < 0.05) extension was observed in all three experiments. Representative data for one experiment are shown. P-values for each individual experiment are shown. *UniProtKB protein accession number. †Relative to lifespan of wild-type feeding on control RNAi strain L4440. RNAi treatments extended mean lifespan and 14% of the RNAi reduced lifespan. In contrast, after fractionation by solubility, only 2% of the tested genes negatively affected lifespan. Taken together, these data sug- gest that insoluble proteins contribute to the relatively short lifespan of wild-type C. elegans. It is possible that lifespan is extended by distinct mechanisms for each protein but as these proteins were identiﬁed using a biochemical approach applied to prepare toxic, disease-associated pro- teins, it is also possible that worm proteins share structural features asso- ciated with toxicity such as an ability to interfere with protein homeostatic machinery. The notion that lifespan is limited by the capacity of the protein homeo- static network is supported by a series of genetic studies in which the expression of components of the network has been manipulated. In C. elegans and Drosophila, over-expression of molecular chaperone genes and their transcriptional regulator HSF-1 led to lifespan extension whereas lowering their expression suppressed longevity (Garigan et al., 2002; Hsu et al., 2003; Walker & Lithgow, 2003; Morley & Morimoto, 2004; Morrow et al., 2004; Wang et al., 2004). Furthermore, mutation of age-1 not only extends lifespan but also resulted in the suppression of protein aggregation in C. elegans expressing polyglutamine (polyQ), Published 2011. This article is a U.S. Government work and is in the public domain in the USA. Aging Cell ª 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland P value 0.0012 <0.0001 0.0017 <0.0001 <0.0001 0.0316 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 0.0037 0.0043 0.0443 <0.0001 <0.0001 0.0052 0.0485 <0.0001 <0.0001 <0.0001 <0.0001 0.0005 <0.0001 <0.0001 0.0197 0.0027 0.0005 <0.0001 <0.0001 0.001 0.0004 <0.0001 0.0334 <0.0001 <0.0001 <0.0001 0.0046 <0.0001 <0.0001 <0.0001 N 75 82 72 76 85 77 62 74 73 79 77 62 72 73 68 60 62 67 74 71 62 58 57 65 62 58 61 61 33 67 62 69 51 56 36 64 60 37 64 60 58