| 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 |
| 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 |
| TCO89 | Tor Complex One | TCO89 deletion increases chronological lifespan, increases mitochondrial oxygen consumption, but decreases mitochondrial and cellular ROS in early stationary phase [21641548]. Deletion of TCO89 cancels out replicative lifespan extension by moderate DR [18690010]. | Budding yeast |
| TOR1 | Target Of Rapamycin 1 | TOR1 deletion extends mean and maximum replicative lifespan by 21 and 25% [16293764] as well as chronological lifespan [21076178]. This lifespan extension is independent of SIR2 and additive with deletion of FOB1 [16293764]. Deletion of TOR1 fails to increase the replicative lifespan of a sir2 mutant [20947565]. Deletion of TOR1 substantially extends chronological lifespan, increasing median survival almost 3-fold (wild-type 4.5 days, tor1 null 12 days), i.e. by 167%. By 21 days in culture, the vast majority of wild-type cells had died (>99.9%), whereas many tor1 null cells remained viable. Deletion of TOR1 also extends the chronological lifespan of the relatively short-lived BY4742 strain, one of the two haploid genetic backgrounds of the widely used Yeast Knockout Collection available from Open Biosystems. Deletion of TOR1 fails to extend chronological lifespan in Petite strains that are unable to respire [17403371]. TOR1 deletion increases replicative lifespan by 30% in the alpha strain and 20% in a strain [19030232]. TOR1 deletion mutant have and increased mean and maximum replicative lifespan by 21% and 6%, respectively [21931558]. Deletion of TOR1 extends replicative lifespan as well as chronological lifespan [21076178] and glucose restriction fails to further extend the long replicative lifespan of tor1Delta [16293764; 16418483; 18225956]. Water starvation (extreme DR) further extends chronological lifespan of tor1 mutants [18225956]. | Budding yeast |
| slcf-1 | SoLute Carrier Family 1 | slcf-1 RNAi or mutation extends the lifespan. slcf-1 mutation increases average lifespan by 40%. DR (by dilution of bacteria on solid medium or by bacterial deprivation) failes to extend slcf-1 mutant's long lifespan and lifespan is even reduced by lowering bacteria concentration (i.e. higher strength of DR) [21040400]. | 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 |
| 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 |
| S6k | RPS6-p70-protein kinase | Ubiquitous overexpression of a dominant-negative form of S6k (alias dS6K) increases mean lifespan by 22% and overexpression of a constitutively active form of S6k decreases mean lifespan by 34% at 29°C. Overexpression of a dominant-negative form of S6k protects mutants from deleterious effects of rich food, as if mimicking the effect of DR [15186745]. | Fruit fly |
| RPL31A | Ribosomal Protein of the Large subunit 31A | Deletion of RPL31A increases mean replicative lifespan by 45% [16293764]. Mean replicative lifespan increases by 35% in the alpha strain and 50% in a strain [19030232; 18423200]. Mean replicative lifespan of the RPL31A deletion mutant increases by 35% in the ORF collection and by 29% in the remade strain [22377630]. RPL31A deletion increases significantly replicative lifespan [17174052]. Deletion of RPL31A extends replicative lifespan and is not further extended by 0.05% glucose restriction [18423200]. | Budding yeast |
| 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 |
| 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 |
| RPD3 | Reduced Potassium Dependency 3 | Deletion of the histone deacetylase gene RPD3 extends lifespan by 41%, independently of an intact Sir silencing complex (in the short lived YSK661 strain) [10512855]. Deletion of RPD3 extends replicative lifespan and there was no additive effect by neither 0.1% glucose nor amino acid restriction [12213553].
RPD3 deletion increases rDNA silencing in a partially SIR2-dependent manner [10082585].
Its effects on chromatin functional state were evidenced by enhanced silencing at the three known heterochromatic regions in the genome, the silent mating type (HM), subtelomeric, and rDNA loci, which occurred even in the absence of SIR3 [10512855]. | Budding yeast |
| RAS2 | Ras-like protein 2 | Overexpression of RAS2 causes a 43% increase in mean and 18% increase in maximum lifespan as well as postpones the age-related increase in generation time. RAS2 deletion causes a 23% decrease in mean and a 30% decrease in maximum lifespan [8034612]. Deletion of RAS2 leads to a longer chronological lifespan [21076178]. Deletion of the RAS2 gene, which functions upstream of CYR1, doubles the mean chronological lifespan by a mechanism that requires Msn2/4 and Sod2 [12586694]. DR further extends chronological lifespan of ras2Delta [18225956]. | 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 |
| 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 |
| PKH2 | Pkb-activating Kinase Homolog 2 | PKH2 deletion increases replicative lifespan by 20% in the alpha strain and by 15% in the a strain [18340043]. Deletion of PKH2 increases chronological lifespan by 29% [22319457] to 34% [21447998] as well as by 19 - 54% (19, 24, 29, 54) in diploid cells [21447998]. PKH2 mutation extends both replicative and chronological lifespan as well as cancels out DR-induced replicative and chronological lifespan extension [21584246]. Mean and maximum replicative lifespan on AL is extended by 38 and 69%, respectively. | 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 |
| Orco | Odorant receptor co-receptor | Loss-of-function mutation in Orco (alias Or83b) results in olfactory defects, altered adult metabolism, enhanced stress resistance, and life-extension. Fully fed female homozygous Or83b null mutants exhibit a 56% increase in median lifespan and a 30% increase in maximum lifespan. Males are also significantly longer-lived, though to a smaller degree and maximum lifespan is not extended. Heterozygous mutants of both sexes show an intermediate longevity. Lifespan of homozygous Orco null mutants is further increased by DR, but the relative increase in median and mean longevity is significantly greater when mutants were maintained in well-fed conditions [17272684].
| Fruit fly |
| nlp-7 | Neuropeptide-Like Protein | nlp-7 RNAi or overexpression reduces oxidative stress resistance and shortens lifespan of wild-type under AL. nlp-7 RNAi significantly reduces extended lifespan of eat-2 mutants, but failed to block lifespan extension of age-1 or clk-1 mutants. Lifespan of nlp-7 mutants increases only moderately by sDR [19783783]. nlp-7 expression is induced under DR via the use of a chemically defined axenic medium [17023606] and by sDR [19783783]. | Nematode |
| NDE1 | NADH Dehydrogenase, External 1 | Overexpression of NDE1 and NDE2 increases intracellular NAD/NADH ratio by lowering NADH concentration and increases replicative lifespan by 20-25%. This lifespan extension is non-additive 0.5% glucose restriction [14724176]. Deletion of NDE1 extends chronological lifespan [16436509]. | 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 |
| 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 |
| 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 |
| 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 |
| 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 |
