Experiments

Lifespan experiments.

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Table 1. First-order interactors of LAGs in the WLN and HLN regulate lifespan in C. elegans

Study: Prediction of C. elegans Longevity Genes by Human and Worm Longevity Networks.
Species: Nematode
Data: network rnai_treatment symbol mean_extension function WLN T23D8.3 T23D8.3 25.7 Translation WLN F37C12.9 rps-14 16.6 Translation WLN T09A5.10 lin-5 16.4 Cell division WLN/HLN C03C10.3 rnr-2 14.2 DNA biosynthesis HLN R02D3.3 R02D3.3 13.0 RNA polymerase II WLN F54E7.2 rps-12 11.6 Translation HLN F10B5.6 emb-27 10.5 Cell division WLN F09F7.3 F09F7.3 8.1 RNA polymerase III HLN F29G9.3 aps-1 7.9 Adaptin HLN T09B4.10 chn-1 7.1 Ubiquitin ligase WLN C38D4.3 mel-28 6.5 Cell division WLN T20B12.8 hmg-4 6.5 Transcription elongation WLN F35G12.10 asb-1 6.4 ATP synthase WLN/HLN F26F4.11 rpb-8 6.4 RNA polymerase II HLN F28D9.1 rsr-1 6.1 Splicing WLN ZK1067.1 let-23 5.6 EGF receptor WLN C47D12.2 C47D12.2 5.5 Unknown WLN K10B3.7 gpd-3 5.3 Glycolysis HLN F18A1.5 rpa-1 5.1 DNA replication HLN C01H6.5 nhr-23 4.9 Molting HLN F31D4.3 fkb-6 2.4 Immunophilin WLN F43E2.7 F43E2.7 2.4 Mitochondrial carrier protein n/a Control n/a 0 n/a WLN R144.2 R144.2 -18.9 mRNA cleavage and polyadenylation WLN K07D4.3 rpn-11 -19.3 Proteasome WLN B0285.1 B0285.1 -22.2 Kinase HLN Y40B1A.4 sptf-3 -22.9 Transcription factor WLN R13G10.1 dpy-27 -23.5 Condensin WLN W07B3.2 gei-4 -27.0 Filament regulation HLN ZK1058.2 pat-3 -28.1 Integrin HLN C52E4.4 rpt-1 -28.4 Proteasome HLN F26H9.6 rab-5 -38.0 Endocytosis HLN D1014.3 snap-1 -39.9 Vesicle fusion HLN K02D10.5 K02D10.5 -48.6 SNARE complex #Postdevelopmental inactivation of 377 first-order LAG interactors in the WLN and HLN identified #104 candidates that conferred an increase in survival, and 55 a decrease. To subject candidates #to a more rigorous assessment of lifespan, 60 candidates (48 long-lived and 12 short-lived) #were inactivated postdevelopmentally in an enhanced RNAi mutant, eri-1. Survival was scored #on alternate days and significance was determined by Kaplan-Meier analysis with a threshold of #p<0.05. Our analysis confirmed the phenotypes of 33 new regulators of longevity, 22 that #increase longevity and 11 that shorten it, listed here with their network association (worm or #human longevity network), gene identifications, percentage change mean lifespan in #comparison to an empty vector RNAi control, and functional annotations. Annotations suggest #that these genes contribute to diverse biological functions, such as translation and energy #metabolism, disruption of which is strongly associated with longevity extension and endocytosis, #which has been identified as a requirement for lifespan extension downstream of insulin/IGF-1 #signaling.

Figure S3. Minimal impact of SIR-2.4 overexpression on stress resistance or lifespan

Study: C. elegans SIRT6/7 homolog SIR-2.4 promotes DAF-16 relocalization and function during stress.
Species: Nematode
Data: genotype mean max wt 21 30 sir-2.4(OE) 21 30

Figure 4. Minimal impact of SIR-2.4 on IIS-induced longevity, DAF-16 nuclear localization induced by reduced IIS, and dauer formation.

Study: C. elegans SIRT6/7 homolog SIR-2.4 promotes DAF-16 relocalization and function during stress.
Species: Nematode
Data: genotype treatment mean max N2 control 15 31 N2 sir-2.4(RNAi) 20 31 daf-2 control 52 93 daf-2 sir-2.4(RNAi) 52 89

TABLE 2 Adult life span profiles A. At 25°

Study: Genetic modifiers of the Drosophila blue cheese gene link defects in lysosomal transport with decreased life span and altered ubiquitinated-protein profiles.
Species: Fruit fly
Data: Genotype;Gender;num;Mean;SD;Max;pvalue #separator=; #temperature=25 Canton-S;Male;264;46.85;12.33;68 dor;Male;295;8.96;3.73;20;<0.0001 dor;Female;98;10.07;3.62;15;<0.0001 dor;Male;106;13.94;2.95;19;<0.0001 hook/hook;Male;110;18.76;8.27;58;<0.0001 hook;Male;338;19.861;7.26;36;<0.0001 carnation;Male;242;17.42;8.69;48;<0.0001 bchs/df clot;Male;330;21.69;10.54;46;<0.0001 bchs/bchs;Male;274;23.7;6.9;37;<0.0001 carmine;Male;351;21.97;6.96;38;<0.0001 light;Male;247;24.92;8.8;61;<0.0001 garnet;Male;111;27.41;11.75;45;<0.0001 ruby;Male;183;31.57;8.842;53;0.0001 atg8aep362;Male;150;41.9;15.4;66;0.0040

TABLE 2 Adult life span profiles A. At 29°

Study: Genetic modifiers of the Drosophila blue cheese gene link defects in lysosomal transport with decreased life span and altered ubiquitinated-protein profiles.
Species: Fruit fly
Data: Genotype;Gender;num;Mean;SD;Max;pvalue #separator=; #temperature=29 white1118;Male;124;36.02;10.97;58 deep orange;Male;136;8.19;2.4;14;<0.0001 rosy;Male;128;19.8;5.98;38;<0.0001 carmine;Male;122;20.69;7.73;36;<0.0001 carnation;Male;121;23.868;8.78;42;<0.0001 bchs/bchs;Male;156;20.08;6.74;36;<0.0001 bchs/Df(2L)clot7;Male;80;22.23;6.3;32;<0.0001 bchs (EP2299);Male;196;25.87;9.09;44;<0.0001 atg8a;Male;153;27.16;7.732;45;<0.0001 garnet;Male;98;32.08;13.84;54;0.0194

Figure 2: Overexpression of CG6783 or CG13890 throughout the whole body extends lifespan, which is associated with diet restriction.

Study: Overexpression of Fatty-Acid-β-Oxidation-Related Genes Extends the Lifespan of Drosophila melanogaster.
Species: Fruit fly
Data: genotype diet mean median max gender #background=white1118 da/+ - 26 32 64 male EPCG6783/+ - 46 - 70 male da>EPCG6783 - 46 58 72 male EPCG13890/+ - 32 - 56 male da>EPCG13890 - 35 42 60 male Act-GS-Gal4>UAS-CG6783 RU- 31 - 65 female Act-GS-Gal4>UAS-CG6783 RU+ 34 - 58 female

Table 1. First-order interactors of LAGs in the WLN regulate lifespan in C. elegans.

Study: Prediction of C. elegans Longevity Genes by Human and Worm Longevity Networks.
Species: Nematode
Data: intervention;symbol;mean_extension;max_extension;function;extra #separator=; #background=N2 Bristol T23D8.3(RNAi);T23D8.3;25.7;34.7;Translation; F37C12.9(RNAi);rps-14;16.6;21.7;Translation; T09A5.10(RNAi);lin-5;16.4;8.7;Cell division; C03C10.3(RNAi);rnr-2;14.2;21.7;DNA biosynthesis;b F54E7.2(RNAi);rps-12;11.6;21.7;Translation; F09F7.3(RNAi);F09F7.3;8.1;21.7;RNA polymerase III; C38D4.3(RNAi);mel-28;6.5;8.7;Cell division; T20B12.8(RNAi);hmg-4;6.5;0.0;Transcription elongation; F35G12.10(RNAi);asb-1;6.4;0.0;ATP synthase; F26F4.11(RNAi);rpb-8;6.4;0.0;RNA polymerase II;b C47D12.2(RNAi);C47D12.2;5.5;8.7;Unknown; K10B3.7(RNAi);gpd-3;5.3;0.0;Glycolysis; R144.2(RNAi);R144.2;-18.9;-25.0;mRNA cleavage and polyadenylation; K07D4.3(RNAi);rpn-11;-19.3;-25.0;Proteasome; B0285.1(RNAi);B0285.1;-22.2;-25.0;Kinase; R13G10.1(RNAi);dpy-27;-23.5;-25.0;Condensin; W07B3.2(RNAi);gei-4;-27.0;-38.0;Filament regulation; # %D mean and %D maximum lifespan (last quartile) were calculated in relation # to control. # Shared genes in WLN and HLN. # doi:10.1371/journal.pone.0048282.t001

Table 2. First-order interactors of LAGs in the HLN regulate lifespan in C. elegans.

Study: Prediction of C. elegans Longevity Genes by Human and Worm Longevity Networks.
Species: Nematode
Data: intervention;symbol;mean_extension;max_extension;function;extra #separator=; #background=N2 Bristol C03C10.3(RNAi);rnr-2;14.2;21.7;DNA biosynthesis;b R02D3.3(RNAi);R02D3.3;13.0;21.7;RNA polymerase II; F10B5.6(RNAi);emb-27;10.5;8.7;Cell division; F29G9.3(RNAi);aps-1;7.9;0.0;Adaptin; T09B4.10(RNAi);chn-1;7.1;8.7;Ubiquitin ligase; F26F4.11(RNAi);rpb-8;6.4;0.0;RNA polymerase II;b F28D9.1(RNAi);rsr-1;6.1;0.0;Splicing; F18A1.5(RNAi);rpa-1;5.1;21.7;DNA replication; C01H6.5(RNAi);nhr-23;4.9;8.7;Molting; Y40B1A.4(RNAi);sptf-3;-22.9;-37.0;Transcription factor; ZK1058.2(RNAi);pat-3;-28.1;-50.0;Integrin; C52E4.4(RNAi);rpt-1;-28.4;-50.0;Proteasome; F26H9.6(RNAi);rab-5;-38.0;-50.0;Endocytosis; D1014.3(RNAi);snap-1;-39.9;-50.0;Vesicle fusion; K02D10.5(RNAi);K02D10.5;-48.6;-72.0;SNARE complex; # %D mean and %D maximum lifespan (last quartile) were calculated in relation to # control. # Shared genes in WLN and HLN. # doi:10.1371/journal.pone.0048282.t002

Figure 5: Hac1-independent resistance to tunicamycin in afg3∆ and rpl20bΔ cells

Study: Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging.
Species: Budding yeast
Data: genotype mean median max num pvalue pvalue pvalue #temperature=30 wt 23.2 24 38 40 - - - afg3 28.4 28 56 160 2.04E-03 - - hac1 25.6 26 40 20 3.22E-01 2.15E-0.1 - afg3;hac1 30.7 32 50 40 2.08E-04 1.16E-01 3.49E-02 # Note: afg3;hac1 max LS is guessed.

Figure 6: Deletion of AFG3 reduces cytoplasmic translation and extends life span by a Sir2-independent, Gcn4-dependent mechanism

Study: Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging.
Species: Budding yeast
Data: genotype treatment mean median max num pvalue pvalue pvalue #temperature=30 fob1 - 32.7 35 52 39 - - - afg3;fob1 - 38.3 40 60 40 2.29E-02 - - wt - 20.3 19 38 80 - - - afg3 - 25.5 24 60 180 1.15E-03 - - sir2;fob1 - 19.7 20 40 39 9.29E-01 1.25E-02 - sir2;fob1;afg3 - 29.1 30 45 40 1.43E-06 1.42E-02 2.95E-05 sir2;fob1 - 30.8 34 46 20 sir2;fob1;afg3 - 46.0 44 78 20 3.60E-02 - - sir2;fob1 DR 42.9 50 64 20 1.67E-02 9.14E-01 - sir2;fob1;afg3 DR 45.3 48 67 20 1.48E-03 8.82E-01 7.56E-01 wt - 21.2 20 38 98 - - - afg3 - 26.7 26 53 260 2.95E-07 - - gcn4 - 22.7 21 42 80 2.24E-01 8.08E-04 - afg3;gcn4 - 18.0 17 50 119 4.10E-03 7.59E-13 4.82E-04 wt - 19.8 19 33 39 afg3 - 24.2 24 45 100 4.77E-03 - - rpl20b - 33.8 36 60 59 1.41E-08 4.34E-08 - afg3rpl20b - 30.3 32 52 40 2.23E-05 1.70E-03 1.24E-01

Supplemental Figure 2: Replicative lifespan curves of control strains sensitive to the tested stresses

Study: Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging.
Species: Budding yeast
Data: genotype mean median max num pvalue #temperature=30 wt 24.4 22 55 125 - sod1 3.8 3 16 76 6.71E-32 wt 26.3 25 48 45 - ctt1 24.9 24 47 43 6.64E-01 wt 28.3 29 46 55 - cta1 29.0 27 54 45 7.68E-01 wt 26.2 26 42 600 - msn2;msn4 29.3 30 57 623 1.76E-08 wt 26.5 26 56 545 hac1 29.1 29 57 543 6.77E-06 wt 24.2 23 51 150 rad52 10.8 33 10 130 # Note for some strain MLS had to be guessed.

Supplemental Figure 3: Growth curves and lifespan curves of respiratory dead or deficient strains

Study: Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging.
Species: Budding yeast
Data: genotype mean median max num pvalue #temperature=30 wt 26.3 26 59 425 - idh1 32.6 33 60 304 1.66E-14 wt 26.6 26 52 764 - idh2 30.7 31 60 595 4.10E-11 wt 25.2 23 43 35 atp5 27.3 27 53 55 4.22E-01 wt 25.3 21 40 15 - coq5 14.3 15 30 15 8.41E-04

Supplemental Figure 4: Unsuppressed growth of afg3∆, yta12∆, and mrpl32∆ and corresponding lifespan curves

Study: Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging.
Species: Budding yeast
Data: genotype mean median max pvalue pvalue pvalue #temperature=30 wt 23.7 23 60 80 - - - mrpl23 28.2 28 51 60 6.82E-03 - - wt 25.8 24 53 60 - - - yta12 20.0 20 41 53 5.45E-03 - - wt 26.7 26 57 160 - - - rho0 26.1 26 50 160 9.41E-01 - - afg3 30.7 31 43 20 3.71E-02 5.25E-02 - afg3;rho0 30.3 32 59 40 3.00E-02 7.74E-02 9.94E-01 W303 18.8 20 36 40 - - - W303;afg3 19.6 21 36 80 6.87E-01 - - # MLS of rho0 and some other are guessed.

Supplemental Figure 5: Cold incubation similarly impairs afg3∆ cell growth and longevity relative to rpl20b∆ cells

Study: Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging.
Species: Budding yeast
Data: genotype mean median max num pvalue #temperature=15 wt 22.3 21 40 40 afg3 23.5 21 49 79 7.21E-01 rpl20b 21.3 22 34 60 8.66E-01 yta12 21.2 22 39 79 8.51E-01

Figure 3 | Reduced vacuolar acidity causes mitochondrial dysfunction by disrupting amino acid homeostasis.

Study: An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast.
Species: Budding yeast
Data: genotype mean median max num pvalue #background=S288c WT 28.95 29 51 32 - AVT1(OE) 37 37 62 32 0.00376 avt1 23 22.5 45 31 0.0045

Figure 2 | Vacuolar acidity is reduced in ageing cells and regulates mitochondrial function and lifespan.

Study: An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast.
Species: Budding yeast
Data: genotype mean median max num pvalue #background=S288c WT 28 28 50 50 - VMA1(OE) 39 39 80 56 0.0002

Figure 4 | Calorie restriction extends lifespan by regulating vacuolar acidity.

Study: An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast.
Species: Budding yeast
Data: genotype treatment mean median max num pvalue #background=S288c WT - 31 31.5 50 32 - WT DR 45 45 75 31 <0.0001 vma2 - 5 5 15 60 <0.0001 vma2 DR 2 2 12 52 0.0398 WT - 29 29 50 38 - WT DR 44 43.5 76 40 <0.0001 VMA1(OE) - 42 43 75 36 <0.0001 VMA1(OE) DR 40 40 64 38 0.076

Supplementary Figure 3. Phenotypes of VPH2 overexpression mimic those observed with VMA1 overexpression.

Study: An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast.
Species: Budding yeast
Data: genotype mean median max num pvalue #background=S288c WT 26 26 50 53 - VPH2(OE) 32 32.5 67 52 0.0054

Figure 3. Increased life span of cardiotrophin 1 (CT-1)–null mice.

Study: Absence of Cardiotrophin 1 Is Associated With Decreased Age-Dependent Arterial Stiffness and Increased Longevity in Mice.
Species: House mouse
Data: genotype median num pvalue #background=C57BL6 #gender=male WT 28 18 - CT-1(null) 33 24 0.007

Figure 1. Regulation of Lifespan by Modulating Genes in the TOR Signaling Pathway

Study: Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway.
Species: Fruit fly
Data: genotype mean max num pvalue #background=w1118 +/da-GAL4 26 31 29 - +/UAS-dTsc1 25 34 109 - da-GAL4/UAS-dTsc1 29 40 136 <0.0001 +/da-GAL4 26 31 92 - +/dTsc2 25 34 118 - da-GAL4/UAS-dTsc2 29 37 112 <0.0001 +/da-GAL4 26 31 92 - +/UAS-dTORFRB 22 31 98 - da-GAL4/UAS-dTORFRB 30 40 126 <0.0001 +/da-GAL4 26 31 92 - +/UAS-dS6KKQ 23 34 115 - da-GAL4/UAS-dS6kKQ 30 40 122 <0.0001 +/da-GAL4 26 31 92 - +/UAS-dS6kSDETE 24 31 40 - da-GAL4/UAS-dS6kSTDETE 16 24 75 <0.0001 +/da-GAL4 58 78 133 - +/UAS-dTsc2 56 74 126 - da-GAL4/UAS-dTsc2 69 88 134 <0.0001 +/da-GAL4 48 79 133 - +UAS-dTORFRB 55 71 128 - da-GAL4/UAS-dTORFRB 72 89 112 <0.0001

Figure 2. Dependence of Lifespan Extension on Overexpression in Specific Tissues

Study: Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway.
Species: Fruit fly
Data: genotype mean max num pvalue #background=w1118 +/gmr-GAL4 31 42 102 - +/UAS-dTsc2 27 33 81 - gmr-GAL4/UAS-dTsc2 27 38 69 <0.01 +/appl-GAL4 32 42 85 - +/UAS-dTsc2 27 33 81 - appl-GAL4/UAS-dTsc2 33 42 108 <0.001 +/24B-GAL4 31 34 67 - +/UAS-dTsc2 27 33 81 - 24B-GAL4/UAS-dTsc2 37 45 107 <0.0001 +/PO188-GAL4 24 28 71 - +/UAS-dTsc2 27 33 81 - PO188-GAL4/UAS-dTsc2 35 45 76 <0.0001 +/DJ634-GAL4 24.6 31 120 - +/UAS-dTsc2 25.3 34 118 - DJ634-GAL4/UAS-dTsc2 30.6 40 120 <0.0001 +/PO163-GAL4 28 34 87 - +/UAS-dTsc2 27 33 81 - PO163-GAL4/UAS-dTsc2 36 45 126 <0.0001 +/DJ634-GAL4 25 31 120 - +/UAS-dTORFRB 22 31 98 - DJ634-GAL4/UAS-dTORFRB 31 37 107 <0.0001 +/DJ634-GAL4 25 31 120 - +/UAS-dS6kKQ 23 34 115 - DJ634-GAL4/UAS-dS6kKQ 31 40 110 <0.0001

Figure 3. Lifespan Extension by dTsc2 Overexpression Is Dependent on the Concentration of Yeast Extract in the Diet

Study: Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway.
Species: Fruit fly
Data: genotype;diet;mean;num;pvalue #temperature=29 #background=w1118 #separator=; +/da-GAL4;0.1% yeast extract;33;125 da-GAL4/UAS-dTsc2;0.1% yeast extract;30;164;<0.3 +/da-GAL4;0.3% yeast extract;31;139 da-GAL4/UAS-dTsc2;0.3% yeast extract;33;138;<0.03 +/da-GAL4;1% yeast extract;30;182 da-GAL4/UAS-dTsc2;1% yeast extract;34;164;<0.0001 +/da-GAL4;3% yeast extract;28;181 da-GAL4/UAS-dTsc2;3% yeast extract;34;154;<0.0001 +/da-GAL4;9% yeast extract;12;150 da-GAL4/UAS-dTsc2;9% yeast extract;24;156;<0.0001

Figure 5. Minocycline effect on life span of female Drosophila melanogaster

Study: Minocycline effect on life and health span of Drosophila melanogaster.
Species: Fruit fly
Data: diet mean max pvalue #background=Oregon #gender=female control 7 23 - minocycline 11 41 <0.0001

Figure 6. Minocycline effect on life span of male Drosophila melanogaster.

Study: Minocycline effect on life and health span of Drosophila melanogaster.
Species: Fruit fly
Data: diet mean max pvalue #background=Oregon #gender=male control 7 32 - minocycline 15 41 <0.0002

Lifespan assay 1. Confirmation of lifespan of spe-9(hc88) animals for library preparations

Study: Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans.
Species: Nematode
Data: genotype mean sem num #background=spe-9(hc88) #temperature=23 spe-9 8.65 0.22 114 spe-9 8.71 0.24 120 spe-9 8.52 0.21 101

Lifespan assay 2. Lifespan of spe-9(hc88) animals exposed to RNAi against alg-1 only during adulthood

Study: Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans.
Species: Nematode
Data: genotype mean sem max num pvalue #background=spe-9(hc88) control(RNAi) 9.32 0.24 - 97 alg-1(RNAi) 7.82 0.16 - 90 <0.0001 control(RNAi) 8.5 0.28 - 80 alg-1(RNAi) 7.68 0.16 - 87 0.0005 control(RNAi) 9.59 0.24 - 93 alg-1(RNAi) 8.17 0.16 - 110 <0.0001 control(RNAi) 9.14 0.33 15 - alg-1(RNAi) 7.89 0.15 10 - <0.0005

Lifespan assay 3. Lifespan of spe-9(hc88) animals at different temperatures

Study: Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans.
Species: Nematode
Data: temperature mean sem num pvalue #background=spe-9(hc88) 23 7.46 0.20 105 27 6.27 0.10 113 <0.0001 15 16.58 0.53 81 <0.0001 23 7.77 0.24 98 27 5.94 0.12 101 <0.0001 15 15.83 0.44 90 <0.0001

Lifespan assay 4. Lifespan of spe-9(hc88) animals exposed to RNAi of daf-2, daf-16 and hsf-1

Study: Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans.
Species: Nematode
Data: treatment mean sem num pvalue #background=spe-9(hc88) control(RNAi) 10.47 0.42 68 daf-2(RNAi) - - 58 <0.0001 daf-16(RNAi) 8.34 0.31 70 <0.0001 hsf-1(RNAi) 5.69 0.22 70 <0.0001 control(RNAi) 9.97 0.41 71 daf-2(RNAi) - - 75 <0.0001 daf-16(RNAi) 8.39 0.32 65 <0.0001 hsf-1(RNAi) 5.76 0.21 75 <0.0001

Figure 3. Deletion or Overexpression of Aging-Associated miRNAs Affects Life Span

Study: MicroRNAs both promote and antagonize longevity in C. elegans.
Species: Nematode
Data: genotype mean max #temperature=20 #strain=N2 control 17 25 mir-71(n4115) 9 12 mir-238(n4112) 14 19 mir-246(n4636) 15 22 mir-239(nDf62) 19 34 control 13 17 mir-71(OE) 16 26 mir-71(OE) 15 23 mir-71(OE) 17 24 control 16 21 mir-246(OE) 17 24 mir-246(OE) 17 24 mir-246(OE) 17 22 control 15 24 mir-239(OE) 13 18 mir-239(OE) 13 20 mir-239(OE) 13 16

Figure 5. miR-239 and miR-71 Function through the IGF-1/Insulin-like and the DNA Damage Checkpoint Pathways

Study: MicroRNAs both promote and antagonize longevity in C. elegans.
Species: Nematode
Data: genotype treatment mean max #temperature=20 #strain=N2 wt - 18 23 mir-239(nDf62) - 20 27 wt daf-16(RNAi) 13 19 mir-239(nDf62) daf-16(RNAi) 13 18 wt daf-2(RNAi) 29 34 mir-239(nDf62) daf-2(RNAi) 26 33 wt - 19 28 mir-71(n4115) - 9 15 wt daf-2(RNAi) 33 40 mir-71(n4115) - 13 21 wt - 20 24 mir-71(n4115) - 10 14 wt daf-16(RNAi) 14 19 mir-71(n4115) daf-16(RNAi) 10 13 wt - 20 24 mir-71(n4115) - 10 14 wt cdc-25.1(RNAi) 22 27 mir-71(n4115) cdc-25.1(RNAi) 11 14

Figure 3. Loss of mir-14 Is Associated with Semilethality, Reduced Lifespan, Stress Sensitivity, and Increased Levels of the Caspase Drice

Study: The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism.
Species: Fruit fly
Data: genotype mean max gender wt 29 42 female mir-14 13 27 female wt 31 42 male mir-14 22 33 male

Fig. 3. Animal survival and growth

Study: The prolongation of the lifespan of rats by repeated oral administration of [60]fullerene.
Species: Norway rat
Data: treatment;mean;median;max;num #separator=; #gender=male #background=Wistar water-treated;29;22;38;6 Olive oil-treated;41;26;58;6 C60-Olive oil-treated;62;42;66;6

Table 3 Parameters of life span in female SHR mice treated and not treated with metformin

Study: Metformin slows down aging and extends life span of female SHR mice.
Species: Norway rat
Data: treatment mean sem median max num pvalue Control 388 29.2 297 814 50 - Metformin 535 31.9 570 898 50 <0.01 # The differences with the controls are significant, p<0.01 (Student t test).

Table 4 Effect of metformin on parameters of life span in female HER-2/neu mice

Study: Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice.
Species: House mouse
Data: treatment mean sem max num pvalue Control 264 3.5 311 34 - Metformin 285 5.2 340 32 <0.05

Figure 3 Increased BubR1 expression protects against spontaneous tumours and extends lifespan

Study: Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan.
Species: House mouse
Data: genotype max num WT 1250 60 T-GFP 882 36 T23 1058 57 T-GFP 882 36 T23 1058 57

Figure S3 Overall and tumor-free survival of T23 animals is extended in males

Study: Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan.
Species: House mouse
Data: genotype max num WT 999 30 T-GFP 882 22 T23 1246 29 T-GFP 882 22 T23 1246 29

Figure S3 Overall and tumor-free survival of T23 animals is extended in females

Study: Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan.
Species: House mouse
Data: genotype max num WT 1057 30 T-GFP 803 14 T23 1003 28 T-GFP 803 14 T23 1003 28

Table 1 Lifespan analyses frh-1 dsRNA constructs - summary statistics

Study: Autophagy induction extends lifespan and reduces lipids content in response to frataxin silencing in C. elegans.
Species: Nematode
Data: genotype;treatment;mean;sem;max;num;pvalue #separator=; WT;control;17.6;0.4;27;-;140;- WT;frh-1 I(RNAi);18.3;0.5;27;130;0.45750 WT;frh-1 II(RNAi);17.2;0.3;27;140;0.37669 WT;frh-1 III(RNAi);16.7;0.4;27;130;0.61293 WT;frh-1 IV(RNAi);20.9;0.5;37;149;0.000001