| 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 |
| 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 |
| 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 |
| MSN2 | Multicopy suppressor of SNF1 mutation 2 | Deletion of MSN2 and MSN4 extends replicative lifespan and is further extended by cyr1::mTn [14741356]. Deletion of MSN2 and MSN4 does not significantly decrease chronological lifespan under AL, but attenuates chronological lifespan extension by water starvation and 0.5% glucose restriction [18225956] as well as cancels out lifespan extension of cyr1::mTn [14741356] and decreases chronological lifespan extension of ras2 deletion mutant [12586694]. Simultaneous deletion of MSN2 and MSN4 has no effect on chronological lifespan, but prevents lifespan extension by RAS2 deletion [12586694]. msn2 msn4 has no effect on replicative lifespan in PSY316, and does not prevent lifespan extension by DR [11000115] or by high osmolarity [12391171]. | Budding yeast |
| MSN4 | Multicopy suppressor of SNF1 mutation 4 | Deletion of MSN2 and MSN4 extends replicative lifespan and is further extended by cyr1::mTn [14741356]. Deletion of MSN2 and MSN4 does not significantly decrease chronological lifespan under AL, but attenuates chronological lifespan extension by water starvation and 0.5% glucose restriction [18225956] as well as cancels out lifespan extension of cyr1::mTn [14741356] and decreases chronological lifespan extension of ras2 deletion mutant [12586694]. Simultaneous deletion of MSN2 and MSN4 has no effect on chronological lifespan, but prevents lifespan extension by RAS2 deletion [12586694]. msn2 msn4 has no effect on replicative lifespan in PSY316, and does not prevent lifespan extension by DR [11000115] or by high osmolarity [12391171]. | Budding yeast |
| LCB4 | Long-Chain Base 4 | Deletion of LCB4 increases replicative lifespan and cancels out replicative lifespan extension of 0.5% glucose DR [18690010]. | Budding yeast |
| 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 |
| 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 |
| Ilp2 | Insulin-like peptide 2 | Flies with an ablation of median neurosecretary cells (which eliminates Ilp2 expression) exhibit a significant increase in mean and maximum lifespan over that of control flies and an increase to oxidative stress and starvation. The mutants also exhibit increased storage of lipid and carbohydrate, reduced fecundity, and reduced tolerance of heat and cold [15708981]. The median and maximum lifespan of females is increased by 33.5% and 40%, respectively. In males the median and maximum lifespan is increased by 10.5% and 27%, respectively [15708981].
Ilp2 RNA interference results in a 24% to 47% increase in median lifespan [19005568].
Ilp2 is transcriptional down-regulated in long-lived mutants. Ilp2 null mutants are significant longer-lived with a 8-13% longer median lifespan, but have a normal DR response. Ilp2 Ilp3 Ilp5 triple null mutants fail to have a normal response to DR. Their response is right shifted, with mutants shorter-lived compared to wild-type on low but longer-lived on high yeast concentrations [20195512]. | Fruit fly |
| HXT17 | HeXose Transporter 17 | HXT17 mutation extends both replicative and chronological lifespan as well as cancels out DR-induced replicative and chronological lifespan extension. Mean and maximum replicative lifespan are extended by 27 and 49%, respectively [21584246]. | Budding yeast |
| GUP1 | Glycerol UPtake 1 | GUP1 deletion extends mean and maximum replicative lifespan by 32 and 30%, respectively, as well as chronological lifespan. DR-induced maximal replicative lifespan extension is not further increased by GUP1 deletion, while gup1 mutant displayed longer chronological lifespan under DR [21584246]. | Budding yeast |
| AIM4 | Altered Inheritance rate of Mi 4 | AIM4 (alias SOY1) deletion increases chronological and replication lifespan, which is non-additive with DR. On AL mean and maximum replicative lifespan are extended by 63 and 69%, respectively. DR appears to decrease aim4-induced replication lifespan extension, indicating a negative interaction. aim4 mutation does not change DR-induced chronological lifespan extension [21584246]. | Budding yeast |
| HHF1 | Histone H Four 1 | HHF1 deletion extends mean and maximum replicative by 45 and 69%, respectively, as well as chronological lifespan. Chronological lifespan extension by HHF1 deletion and DR is non-synergistic. DR appears to extend replicative lifespan more when combined with hhf1 mutation, whereas DR does not change hhf1-induced replicative lifespan extension, suggesting a positive interaction [21584246]. | Budding yeast |
| FRE6 | Ferric REductase 6 | FRE6 deletion increases mean replicative lifespan by 14% and cancels out the lifespan extending effect of DR [22912585]. | Budding yeast |
| RCR2 | Resistance to Congo Red 2 | RCR2 deletion extends mean replicative lifespan by 18% and cancels out the lifespan extending effect of DR [22912585]. | Budding yeast |
| OPT2 | OligoPeptide Transporter 2 | OPT2 deletion increases mean and maximum replicative lifespan by 23 and 9%, respectively, and cancels out the lifespan-extending effect of DR [22912585]. | Budding yeast |
| ATG11 | AuTophaGy related 11 | ATG11 deletion extends replicative lifespan under AL and abrogates DR-lifespan extension [18690010]. | Budding yeast |
| elt-3 | Erythroid-Like Transcription factor 3 | Expression of elt-3 decreases with development and aging. elt-3 RNAi extends maximum lifespan and totally cancels out the daf-2 or DR-induced (eat-2) lifespan extension [18662544]. | Nematode |
| ADE4 | ADEnine requiring 4 | ade4 mutation extends chronological lifespan, but not replicative lifespan, and is non-additive with 0.5% glucose or amino-acid DR on chronological lifespan extension. ADE4 deletion in atg16 mutants results only in a partial extension of the chronological lifespan by 0.5% glucose DR [20421943]. | Budding yeast |
