| nhr-62 | Nuclear Hormone Receptor family | NHR-62 is required for metabolic and physiologic responses associated with DR-induced longevity. *nhr-62* mediates the longevity response of *eat-2* mutants and blunts the longevity by bacterial food dilution [Heestand, et al. 2012].
Mutation in *nhr-62* suppresses the lifespan extension of eat-2(ad465) animals (p<0.001) [Heestand et al. 2013].
Wild-type (N2) worms with extrachromosomal array dhEx627 (carrying a wild-type nhr-62) exhibit a significant increase in lifespan compared to wild-type (p<0.001) [Heestand et al. 2013]. | 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 |
| nekl-2 | NEK (NEver in mitosis Kinase) Like 2 | RNA intereference of nekl-2 decreases lifespan by 24% and suppresses lifespan extension by eat-2 mutation [22829775]. | 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| shk-1 | SHaKer family of potassium channels 1 | shk-1 encodes a shaker family of potassium channel which functions in muscle [21059759], is expressed in sensory neurons [16899454], and downregulated in space. Mutation or RNA interference of shk-1 extends lifespan on NGM agar covered with killed or live bacteria as well as in liquid culture medium. shk-1 RNAi extends mean, 75%ile, and maximum lifespan by 16, 15, and 22%. shk-1(RB1392) mutation extends mean, 75%ile, and maximum lifespan by 19-22, 19-21, and 20-24%. Lifespan extension by unc-17 mutation is totally abolished by RNAi inactivation of either daf-16 or skn-1. eat-2 RNAi shortens the lifespan of shk-1 mutants. RNAi inactivation of shk-1 reduces Q35 aggregation [22768380].
Mutation and RNAi of shk-1 enhance pheromone-induced dauer formation [22768380].
| Nematode |
| F57A8.4 | Protein F57A8.4 | F57A8.4 encodes a rhodopsin-like G-protein coupled receptor that is known to sense light [11493519] and is downregulated in space.
Mutation or RNA interference of F57A8.4 extends lifespan on NGM agar covered with killed or live bacteria as well as in liquid culture medium. F57A8.4 RNAi extends the mean, 75%ile and maximum lifespan by 34, 39, and 61%. F57A8.4(tm4341) mutation extends the mean, 75%ile, and maximum lifespan by 18-38, 21-25, and 42-68%. Lifespan extension by gar-3 mutation is not abolished by RNAi inactivation of either daf-16 nor skn-1. eat-2 RNAi shortens the lifespan of F57A8.4 mutants [22768380].
Mutation and RNAi of F57A8.4 suppresses pheromone-induced dauer formation [22768380].
| Nematode |
| cha-1 | abnormal CHoline Acetyltransferase 1 | cha-1 encodes a choline acetyltransferase which is expressed in motor [18041778] neurons and downregulated in space. Mutation or RNA interference of cha-1 extends lifespan on NGM agar covered with killed or live bacteria as well as in liquid culture medium [22768380]. cha-1(TY1652) mutation extends mean, 75%ile, and maximum lifespan by 23, 29, and 38%. The cha-1(PR1152) allele extends mean, 75%ile, and maximum lifespan by 22-49, 18-25, and 11-21%. Lifespan extension by cha-1 mutation is not abolished by daf-16 RNAi inactivation. eat-2 RNAi shortens the lifespan of cha-1 mutants. RNAi inactivation of cha-1 reduces Q35 aggregation [22768380].
cha-1 participates in determining pharyngeal pumping rate to affect food intake [6698395]. | Nematode |
| aakg-2 | AMP-Activated protein Kinase Gamma subunit 2 | aakg-2 overexpression extends mean, median, and maximum lifespan by 47, 45, and 35%. Overexpression of aakg-2 toegther with D. rerio ucp2 was non-additive with sDR [22737090]. | Nematode |
| unc-51 | UNCoordinated-51 | unc-51(e369) mutation reduces mean but extends maximum lifespan. unc-51(e369) mutation reduces lifespan of eat-2(ad1116) mutants to that of wild-type [18219227]. | Nematode |
| ckr-1 | CholecystoKinin Receptor homolog 1 | ckr-1 RNAi significantly reduces lifespan of eat-2 but not that of age-1 nor clk-1 mutants [19783783]. | Nematode |
| mdt-15 | MeDiaTor 15 | mdt-15(tm2182) mutation does not affect lifespan on ad libitum, but further increases the lifespan when combined with DR (starting at the 4th day of adulthood) even more as wild-type [22132200]. | Nematode |
| rab-10 | RAB family | rab-10 RNA interference significantly extends lifespan of wild-type by 14 - 16%, of daf-16 mutants by 47%, and of daf-2 by 46%, but fails to significantly further extend lifespan of eat-2 mutants. rab-10 RNAi does not affect pumping, but similar to DR reduces and delays reproduction as well as cause a slender appearance. rab-10 mRNA is 2-fold downregulated in response to DR [16103914]. rab-10 RNAi significantly reduces paralysis in Q35YFP transgenic animals [18331616]. | Nematode |
| let-363 | LEThal 363 | let-363 RNAi significantly extends the lifespan of wild-type, but does not further extend the long lifespan of eat-2 mutant [17266679]. let-363 RNAi led to an average increase in lifespan of 8% in wild-type and 3% in eat-2 background. let-363 works synergistically with eat-2 mutation. Inhibition of let-363 leads to a phenotype similar to starved animals and modest increase in lifespan [16720740]. DR fails to significantly extend lifespan of let-363 RNAi-treated animals [19079239]. RNAi or mutation of let-363 results in a doubling of lifespan. RNAi of let-363 begun at hatching extends lifespan to the same extent as RNAi begun at the first day of adulthood. RNAi of let-363 fails to further extend the lifespan of daf-2(e1370) mutants [14668850]. Lifespan extension of let-363 RNAi does not require daf-16, as mutations in daf-16 do not suppress the long-lived phenotype of let-363 RNAi animals [14668850]. let-363 RNAi slightly extends lifespan of daf-16 mutation [16720740]. RNAi of let-363 causes many phenotypes similiar to daf-2 mutation: lipid accumulation in intestinal cells, reduced fertility, and reduced viability due to embryonic/larval arrest [14668850]. The let-363(h111) allele has no significant effect on lifespan [15253933]. Disruption of let-363 by RNAi appears to incomplete as lifespan is not extended as much asin let-363 mutants [14668850]. The let-363(h114) allele at 25.5 degree Celsius extends mean lifespan by 150% [14668850].
The absence of LET-363 activity causes developmental arrest at the L3 stage [12225660]. | Nematode |
| vps-34 | related to yeast Vacuolar Protein Sorting factor 34 | vps-34 RNAi does not significantly change lifespan of wild-type, but cancels out the lifespan extension effect of eat-2 mutation [18282106]. | Nematode |
| rheb-1 | RHEB (Ras Homolog Enriched in Brain) hom | rheb-1 RNAi extends lifespan by mimicking the DR effect. Under AL condition, rheb-1 RNAi extends lifespan by 19.1% and the longevity-promoting effects of two DR regimens sDR and intermittent fasting are abolished [19079239]. Knockdown of rheb-1 by RNAi only during the adulthood increases mean, median and 75th %ile lifespan by 18-25, 25 and 23-24%, respectively, but failed so in skn-1 or daf-16 mutant (with and without FUdR). Knockdown of rheb-1 dramatically enhances stress tolerance in an skn-1, but not daf-16-dependent manner [22560223]. | Nematode |
| hsp-12.6 | Heat Shock Protein | hsp-12.6 loss-of-function mutation significantly extends lifespan under AL and significantly suppresses intermittent fasting (IF)-induced increase in lifespan, to a similar extend to that of daf-16 mutation. HSP-12.6 expression is induced by fasting in various tissues, including body wall muscle and neuronal systems. hsp-16.2 is one of downstream targets of DAF-16 in IF-induced longevity. The extent of IF-induced longevity in daf-16 hsp-12.6 double mutant is similar to that of single hsp-12.6 or daf-16 mutants. hsp-12.6 and daf-16 function in same signaling pathway. Low insulin/IGF-like signaling in daf-2 results in constitutive activation of DAF-16 and higher expression of hsp-12.6 [19079239]. Expression of hsp-16.2 predicts longevity [13-18 in 22829775]. | Nematode |
| hif-1 | HIF (hypoxia inducible factor) homolog 1 | hif-1 mutation does not suppress lifespan extension of bDR or eat-2 mutation [19372390]. hif-1 deletion extends lifespan by 24% and inhibition of hif-1 by RNAi also extends adult lifespan. hif-1 mutation extends lifespan under AL, but does not further extend lifespan extension under modified sDR. Activation of hif-1 by egl-9 deletion diminishes lifespan extension by modified sDR. hif-1 acts independent of insulin-like signaling: Lifespan extension by hif-1 suppression does not require DAF-16, because inhibition of hif-1 by RNAi extends lifespan of wild-type and daf-16 null mutant to a similar level. hif-1 RNAi further extends the lifespan of daf-2 mutants. hif-1 is in the TOR pathway, downstream of S6K/rsks-1: Inhibition of hif-1 by RNAi does not further extend lifespan of daf-15 heterozygous mutants. Lifespan extension by deletion mutant of rsks-1 is fully suppressed by egl-9 mutation. hif-1 mutation does not further extend rsks-1 lifespan. pha-4 RNAi slightly reduces lifespan in wild-type and hif-1 mutants, but hif-1 mutation extends lifespan of animals treated with control or pha-4 RNAi to a similar level [19461873]. | Nematode |
