| YHB4 | Yeast HemogloBin-like protein 4 | sfa1;yhb1 double mutant cancels out the ability of moderate DR to extend replicative lifespan, but not chronological lifespan. Indicating that NO homeostasis during DR-induced replicative lifespan extension is crucial. Deleting YHB1 partially abolished DR-induced replicative lifespan extension, whereas deleting SFA1 alone had no effect. Yhb1 and Sfa1 may play redundant roles [21584246]. | Budding yeast |
| sams-1 | S-Adenosyl Methionine Synthetase 1 | sams-1 RNAi significantly extends lifespan of wild-type by 14 - 15%, of daf-16 mutant by 30% and daf-2 by 55%, but fails to significantly further extend lifespan of eat-2 mutants. mRNA level of sams-1 is 2-fold reduced in eat-2 mutants. Like DR, sams-1 RNAi reduces brood size and slightly reproductive timing as well as causes a slender phenotype [16103914]. sams-1 RNAi significantly reduces paralysis in Q35YFP transgenic animals [18331616]. | Nematode |
| drr-1 | Dietary Restriction Response (WT but not eat-2 lifespan increased) 1 | RNAi of drr-1 starting at L1 extends mean, 25%ile and median lifespan by 3, 8 and 8% [15998808]. drr-1 RNAi significantly extends mean lifespan of wild-type by 37 - 44%, of daf-16 mutants by 18%, and of daf-2 mutants by 14%, but does not extend significantly the lifespan of eat-2 mutants. drr-1 RNAi does not affect pumping, but similar to DR reduces and delays reproduction as well as causes a slender appearance. drr-1 mRNA is 2-fold downregulated in response to DR [16103914]. | Nematode |
| CG5389 | — | RNAi of complex V subunit CG5389 results in increased mean longevity under standard laboratory food conditions (3% yeast) in males. RNAi started from the development results in a mild lifespan increase in both sexes (3-11% in females and 3-8% in males). Post-developmental RNAi and silencing limited to neurons has variable effects with reduction in lifespan of up to 9% [19747824]. Under rich media conditions CG5389 knockdown throughout development and adulthood increases mean lifespan by 26% and abolished the lifespan extension by DR (started in the adulthood) in males. Suppression of CG5389 only during the adulthood either via RNAi by tub-GS or via oligomycin (a specific inhibitor of complex V) feeding prevents an increase in longevity under DR (started in the adulthood) in males [19968629]. | Fruit fly |
| icl-1 | IsoCitrate Lyase homolog 1 | RNAi knockdown of icl-1 (alias gei-7) starting at hatching or only during the adulthood significantly extends lifespan of wild-type, but does not alter, or even shortens the lifespan of eat-2 mutants [22810224]. | Nematode |
| fat-2 | FATty acid desaturase 2 | RNAi knockdown of fat-2 starting at hatching or only during the adulthood significantly extends lifespan of wild-type, but does not alter, or even shortens the lifespan of eat-2 mutants. FAT-2 is downregulated in eat-2 [22810224].
| Nematode |
| acdh-1 | Acyl CoA DeHydrogenase 1 | RNAi knockdown of acdh-1 starting at hatching or only during the adulthood significantly decreases lifespan of eat-2 without affecting wild-type lifespan. ACDH-1 significantly upregulated in eat-2. Increased content of ACDH-1 is, at least partially, required for lifespan-extension by DR [22810224]. | Nematode |
| wwp-1 | WW domain Protein (E3 ubiquitin ligase) 1 | RNA interference of wwp-1 decreases median lifespan by 9% in wild-type animals and 24% in daf-2 mutants [18006689]. Loss of wwp-1 function by RNAi or mutation reduces lifespan at 25 degree Celsius, but not 20 degree Celsius. wwp-1 overexpression extends lifespan by up to 20%. Reduced levels of wwp-1 completely suppress the extended longevity of eat-2 mutants. Lifespan of wwp-1 mutants across entire food concentration range by bacterial dilution in liquid culture or on solid plates does not noticeable change. There is no difference in wwp-1 mRNA levels under AL and DR. RNAi reduction of pha-4, but not of daf-16 suppresses increased longevity by wwp-1 overexpression. Mutations in iron sulphur component of complex III, isp-1, increases longevity by reducing mitochondrial function. wwp-1 RNAi does not suppress the extended lifespan of isp-1 mutants and has only minor suppressive effects on lifespan of another mitochondrial mutant, clk-1, and in cyc-1 RNAi treated worms. RNAi depletion of wwp-1 has no effect on long lifespan of daf-2 mutants [19553937]. | Nematode |
| wnk-1 | mammalian WNK-type protein kinase homolog 1 | RNA interference of wnk-1 decreases lifespan by 9% and suppresses lifespan extension by eat-2 mutation [22829775]. | Nematode |
| unc-52 | UNCoordinated 52 | RNA interference of unc-52 in adulthood extends mean lifespan by 11% [17411345]. RNAi knockdown of unc-52 starting at hatching or only during the adulthood significantly decreases lifespan of eat-2 without affecting wild-type lifespan. UNC-52 levels are elevated in eat-2 mutants. Increased content of UNC-52 is, at least partially, required for lifespan-extension by DR [22810224]. | Nematode |
| smk-1 | SMEK (Dictyostelium Suppressor of MEK null) homolog 1 | RNA interference of smk-1 completely suppresses the extended longevity of daf-2 mutations and partly the life-extension of clk-1 mutants. smk-1 RNAi decreases mean and maximum lifespan of similar level than daf-16 knockdown [16530049]. smk-1 RNAi only slightly shortens the lifespan of wild-type worms, but abolishes the extended lifespan of eat-2 mutants [17476212]. Loss of smk-1 by temperature sensitive allele suppresses the extended lifespan under optimal bDR, but not the response to DR itself [17476212]. | Nematode |
| sbds-1 | Shwachman-Bodian-Diamond Syndrome protein homolog 1 | RNA interference of sbds-1 decreases median lifespan by 24% in daf-2 mutants [18006689]. RNAi knockdown of sbds-1 starting at hatching or only during the adulthood significantly decreases lifespan of eat-2 without affecting wild-type lifespan. SBDS-1 are elevated in eat-2 mutants. Increased content of SBDS-1 is, at least partially, required for lifespan-extension by DR [22810224]. | Nematode |
| pyc-1 | PYruvate Carboxylase 1 | RNA interference of pyc-1 starting at hatching or only during the adulthood significantly decreases eat-2 lifespan without affecting the lifespan of wild-type. PYC-1 is downregulated in eat-2 mutants [22810224]. | Nematode |
| pod-2 | Polarity and Osmotic sensitivity Defect 2 | RNA interference of pod-2 starting at hatching or only during the adulthood significantly decreases eat-2 lifespan without affecting the lifespan of wild-type. POD-2 is downregulated in eat-2 [22810224]. | Nematode |
| phi-50 | — | RNA interference of phi-50 decreases mean lifespan by 29% and suppresses lifespan extension by isp-1 and eat-2 mutation but does not significantly affect lifespan extension by daf-2 [22829775]. | Nematode |
| skn-1 | SKiNhead 1 | RNA interference of or mutations in skn-1 prevent the life-extension effects of dietary restriction [17538612]. skn-1 transgenes that overexpress a constitutive nuclear form of SKN-1 in the intestine extend the mean lifespan by 5-21%, independently of DAF-16 [18358814]. skn-1 mutation does not alter lifespan under AL, but cancels out the lifespan extension effect of lDR or food variation at all. Response to lDR in skn-1 mutant is restored by ectopic expression of skn-1 in ASI neurons and gut. Ectopic expression of skn-1b in ASI neurons rescued lDR longevity defects of skn-1. Ablation of ASI neurons completely suppresses the response to DR in wild-type or daf-16 mutants and cause a small increase in basal longevity of wild-type but not daf-16 mutants. lDR significantly increases SKN-1 expression in ASI neurons. lDR worms exhibit elevated respiration, which is absent in skn-1 mutants. skn-1 is necessary for increased respiration and the increase in respiration is necessary for lDR longevity effect, because two different inhibitors of mitochondrial electron transport chain complex III, myxothiazol and antimycin, suppress lDR longevity without shortening lifespan under AL. In contrast, the long life of a daf-2 mutant is not affected by antimycin. Some isoforms of SKN-1 are expressed from an operon downstream of bec-1. Beclin-1 mediates autophagy induced by nutrient deprivation. Therefore, skn-1 might be regulated by nutritional stress [17538612]. IF significantly extends lifespan of skn-1 mutants [19079239]. sDR extends lifespan of a skn-1 loss-of-function mutant (which displays a premature stop codon in all three isoforms) and wild-type to a similar extent [19239417].
skn-1(zu67) mutation decreases mean, median, and maximum lifespan by 11-23, 13-28 and 12-23%, respectively, and totally cancels out lifespan extension by ragc-1 RNAi [22560223].
| Nematode |
| l(3)neo18 | lethal (3) neo18 | RNA interference of l(3)neo18 in females increases mean lifespan by 14-18% when applied during development and adulthood in the whole organism and by 8-24% when applied in the neurons. The effect is more variable in males. A consistent increase (8-18%) is however observed for whole organisms RNAi in adults [19747824].
l(3)neo18 (alias CG9762) is translational upregulated upon DR. Under rich nutritional conditions lifespan of l(3)neo18 RNAi knockout animals is indistinguishable from wild-type, while upon DR, lifespan extension is diminished in males and females [19804760].
| Fruit fly |
| ins-7 | INSulin related 7 | RNA interference of ins-7 extends the mean lifespan by 55% at 20 degree Celsius in N2 rrf-3(pk1426) [12845331]. ins-7 RNAi significantly extends lifespan under AL. Treating wild-type with 2% glucose produced pattern of gene expression that overlaps significantly with that produced by genetic inhibition of daf-16 activity in daf-2 mutants. This results in changes in expression of several insulin-like genes, including DAF-16 target gene ins-7. Addition of glucose triggers an increased ins-7:GFP expression. Glucose suppresses the extended lifespan by ins-7 RNAi [19883616]. RNAi of ins-7 does not further extend the lifespan in daf-2 mutants [12845331]. ins-7 is repressed in animals with reduced daf-2 activity and elevuated in animals with reduced daf-16 activity. | Nematode |
| hsf-1 | Heat Shock Factor 1 | RNA interference of hsf-1 suppresses normal dauer formation and life-extension due to insulin-like signaling [14668486]. hsf-1 overexpression extends mean, median, and maximum lifespan by 37, 35, and 29%[22737090]. hsf-1 RNAi abrogates lifespan extension by daf-2(e1370) mutation, but not eat-2(ad1116) or isp-1(qm150). HSF-1, like DAF-16, is required for daf-2 mutations to extend lifespan [12750521]. A mutant allele of hsf-1 slightly decreases lifespan under AL, but cancels out the lifespan extension effect of bDR. hsf-1 RNAi also prevents lifespan extension by bDR. bDR significantly reduces paralysis of Q35YFP or ABeta42 transgenic animals and hsf-1 RNAi totally cancels this effect. DR confers a general protective effect against proteotoxicity and promotes longevity by a mechanism involving hsf-1 [18331616]. Glucose or glycerol does not shorten the lifespan of hsf-1 mutants. Glucose treatment completely suppresses the long lifespan caused by hsf-1 overexpression [19883616]. sDR extends the lifespan of hsf-1 mutant with a premature stop codon, that eliminates activation domain, and that of wild-type to a similar extent [19239417]. hsf-1 RNAi attenuates lifespan extension by bDR, but only partially that of daf-2 mutation. hsf-1 RNAi attenuates protection against oxidative stress by bDR. hsf-1 expression is induced by bDR [19924292]. RNAi of hsf-1 shortens median and maximum lifespan by approximately 35%. hsf-1 RNAi animals exhibit phenotypes associated with accelerated aging (as assyed by Nomarsky microscopy) [12136014]. | Nematode |
| drr-2 | Dietary Restriction Response (WT but not eat-2 lifespan increased) 2 | RNA interference of drr-2 extends lifespan [15998808]. drr-2 RNAi extends lifespan of wild-type by 10-16%, but fails to significantly extend lifespan of daf-2 mutants or eat-2 mutants. drr-2 RNAi keeps a normal, well-fed appearance and normal reproduction. drr-2 mRNA expression is 2-fold reduced in eat-2 mutants [16103914]. drr-2 RNAi significantly reduces paralysis in Q35YFP transgenic animals [18331616]. drr-2 overexpression suppresses lifespan extension by eat-2 mutation and solid plate-based DR [20456299]. | Nematode |
| cpf-2 | Cleavage and Polyadenylation Factor 2 | RNA interference of cpf-2 decreases mean lifespan by 6% and suppresses lifespan extension by eat-2 mutation [22829775]. | Nematode |
| acdh-12 | Acyl CoA DeHydrogenase 12 | RNA interference of acdh-12 starting at hatching or only during the adulthood significantly decreases eat-2 lifespan without affecting the lifespan of wild-type [22810224]. | Nematode |
| vit-5 | VITellogenin structural genes (yolk protein genes) 5 | RNA interference against vit-5 extends mean lifespan by 10-22%. vit-5 is differentially transcribed in daf-16 and daf-2 RNAi animals [12845331]. RNAi knockdown of vit-5 starting at hatching or only during the adulthood significantly extends lifespan of wild-type, but does not alter, or even shortens the lifespan of eat-2 mutants [22810224]. | Nematode |
| atg-7 | AuTophaGy (yeast Atg homolog) 7 | RNA interference against atg-7 shortens mean lifespan by 23% and maximum lifespan by 30% in a eat-2 mutant background but not in wild-type animals. Thus, atg7 RNAi does not affect lifespan of wild-type, but totally cancels out the lifespan extension effect of eat-2 mutation [17912023]. | Nematode |
| asp-3 | ASpartyl Protease 3 | RNA interference against asp-3 significantly reduces lifespan of eat-2(ad1116) mutants, without any significant affect on the lifespan of wild-type. Mean and 75%ile lifespan of eat-2 mutants is reduced by 13-14% and 5-9% by asp-3 RNAi. ASP-3 is upregulated in eat-2 mutants [22810224]. | Nematode |
