| sir-2.1 | Yeast SIR related 1 | sir-2.1 deletion slightly reduces lifespan of wild-type [16860373]. sir-2.1 overexpression extends lifespan by about 50% and this lifespan extension depends on DAF-16 activity as it is suppressed by mutation in daf-16 and it does not synergize with daf-2 [11242085]. sir-2.1 suppresses longevity of unc-13 and eat-2, but not daf-2 or unc-64 mutants. sir-2.1 is therefore partially required for lifespan extension from mutation of eat-2 [16860373], but is completely independent for lifespan extension from DR using a reduced feeding protocol [Kaeberlein et al. in press]. sDR increases lifespan of wild-type and sir-2.1 mutants to the same extent [19239417].
Overrexpression of sir-2.1 synergizes with TGF-beta mutation (daf-4 and daf-1) for dauer formation [11242085]. | Nematode |
| YPT7 | Yeast Protein Two 7 | YPT7 deletion decreases replicative lifespan by 15% in the alpha strain [18340043]. Deletion of YPT7 cancels out replicative lifespan extension of 0.5% glucose restriction and results under DR also into a shorter replicative lifespan than under AL [18690010]. | Budding yeast |
| 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 |
| 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 |
| 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 |
| VPS8 | Vacuolar Protein Sorting 8 | Lack of VPS8 reduces lifespan under starvation conditions to a level similiar to that of wild-type cells incubated in synthetic complete medium and therefore blocked the lifespan-extending effect of DR [20657825]. | Budding yeast |
| VPS30 | Vacuolar Protein Sorting 30 | VPS30 deletion prevents chronological lifespan extension induced by amino-acid DR [20421943]. | Budding yeast |
| VPS21 | Vacuolar Protein Sorting 21 | Lack of VPS21 reduces lifespan under starvation conditions to a level similiar to that of wild-type cells incubated in synthetic complete medium and therefore blocked the lifespan-extending effect of DR [20657825]. | Budding yeast |
| VPS20 | Vacuolar Protein Sorting 20 | VPS20 deletion decreases mean and maximum replicative lifespan by 16% and 19%, respectively, and additionally cancels out the DR-induced replicative lifespan extension [22912585]. | Budding yeast |
| VAM7 | VAcuolar Morphogenesis 7 | VAM7 deletion decreases replicative lifespan under AL and blocked DR-mediated lifespan extension. Replicative lifespan decreases by 70% on DR in VAM7 deletion mutant [18690010]. | Budding yeast |
| VMA2 | Vacuolar Membrane Atpase 2 | VMA2 deletion mutants have a reduced ΔΨ and mitochondrial morphology similar to aged cells. The restoration of the vacuolar acidity in daughter cells requires V-ATPase activity as it is eliminated in VMA2 deletion mutant cells [23172144]. VMA2 deletion mutation decreases the mean replicative lifespan by 80% in the alpha strain [18340043]. Deletion of VMA2 decreases mean, median and maximum replicative lifespan by 84%, 84% and 70%, respectively. DR (0.5% glucose restriction) does not extend the replicative lifespan of VMA2 and shortens it even more [23172144]. | Budding yeast |
| VMA1 | Vacuolar Membrane Atpase 1 | Overexpression of VMA1 increases vacuolar acidity and suppresses age-induced mitochondrial dysfunction of aged cells (17 or 18 cell divisions) which requires the V-ATPase activity. VMA1 overexpression significantly increases mean, median and maximum lifespan by 39 - 45%, 39 - 48% and 50 - 60%, respectively. DR (0.5% glucose restriction) does not further increase the lifespan of VMA1 overexpression strain [23172144].
| Budding yeast |
| ucp2 | uncoupling protein 2 | Overexpression of zebrafish's ucp2 in nematode increases mean, median, and maximum lifespan by 42, 40, and 26%, which is non-additive with sDR [22737090]. | — |
| 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 |
| 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 |
| ubc-18 | UBiquitin Conjugating enzyme 18 | ubc-18 overexpression is unable to extend lifespan (possibly, UBC-18 is not limiting for WWP-1 function in lifespan). Loss of ubc-18 function by mutation or RNAi reduces lifespan at 25 degree Celsius, but only slightly at 20 degree Celsius. RNAi depletion of ubc-18 completely suppresses increased longevity of eat-2 mutants. RNAi depletion of ubc-18 has no effect on long lifespan of isp-1 or daf-2 mutants. Combined knockdown of wwp-1 and ubc-18 by RNAi does not shorten lifespan any further than RNAi of either single gene. Knockdown of ubc-18 suppresses extended lifespan of wwp-1 overexpression [19553937]. | 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 |
| trx-1 | ThioRedoXin 1 | Thioredoxins regulate many cellular redox processes. trx-1 is mainly associated with neurons and is expressed in ASJ ciliated sensory neurons and to some extent also on the posterior-most internal cells. trx-1 reduces protein disulfides in the presence of a heterologous thioredoxin reductase. trx-1 null mutant display reduced mean and maximum lifespan [16387300]. Mutants with a deletion in the trx-1 gene display a decrease in lifespan and are sensitive to oxidative stress [16324156]. trx-1 overexpression extends lifespan in wild-type but not in eat-2 mutants. trx-1 deletion completely suppresses the lifespan extension caused by eat-2 mutation, but only partially suppresses that by daf-2 or osm-5 mutations. Ectopic expression of trx-1 in ASJ neurons (but not in the intestine) in trx-1 mutants rescues the lifespan-extension conferred by eat-2 mutation. trx-1 overexpression extends lifespan of wild-type but not in eat-2 mutants. trx-1 deletion almost completely suppresses lifespan extension induced by dietary deprivation (DD). DD upregulates trx-1 expression in ASJ neurons. DR activates trx-1 in ASJ neurons which in turn triggers a trx-1-dependent non-cell autonomous mechanism to extend adult lifespan [21334311].
| Nematode |
| TSA1 | Thiol-Specific Antioxidant 1 | A gain-of-function allele of peroxiredoxin (thioredoxin peroxidase, Tsa1) causes a dominant oxidative stress-resistance and robust premature aging phenotype with reduced mean lifespan. These effect is not provoked by altered Tsa1 levels, nor can it be stimulated by deletion, haploinssufficiency or overexpression of wild-type allele [20729566]. Disruption of TSA1 shortens chronological lifespan [15129730]. Replicative lifespan extension by DR in sir2;fob1 double mutant is reduced by TSA1 deletion mutant. Wild-type cells require TSA1 to fully extend lifespan. Mutation in CDC35 (adenylate cyclase), a genetic mimetic of DR, is dependent on TSA1 to extend lifespan [21884982]. | 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 |
| SLM4 | Synthetic Lethal with Mss4 4 | SLM4 deletion blocks replicative lifespan extension by moderate DR, but does affect lifespan on AL significantly [22912585]. | Budding yeast |
| SUR4 | SUppressor of Rvs161 and rvs167 mutations 4 | Deletion of SUR4 cancels out replicative lifespan extension of 0.5% glucose DR [18690010]. | Budding yeast |
| SRX1 | SulfiRedoXin 1 | Extra copy of SRX1 counteracts age-related hyperoxidation of Tsa1 and extends replicative lifespan by 15 - 20% in a TSA1-dependent manner. Replicative lifespan extension in sir2;fob1 double mutant by DR is reduced by SRX1 deletion. Wild-type cells require SRX1 to fully extend lifespan. DR fails to further extend replicative lifespan of cells carrying an extra copy of SRX1. Mutation in CDC35 (adenylate cyclase), a genetic mimetic of DR, is dependent on SRX1 to extend replicative lifespan [21884982]. | 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 |
| 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 |
