| 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 |
| SCH9 | — | Transposon-mediated mutagenesis of SCH9, which encodes for a serine threonine kinase homologous to Akt/PKB, increases resistance to oxidants and thermal stress as well as extends chronological lifespan by 30%. SCH9 deletion increases chronological lifespan by up to threefold. Stress-resistance transcription factors Msn2/Msn4 and protein kinase Rim15 are required for this life-extension. Deletion of the mitochondrial antioxidant enzyme superoxide dismutase gene SOD2 prevents the increased chronological lifespan caused by SCH9 deletion [11292860]. Mutations that decrease the activity of the Ras/Cyr1/PKA pathway also extend longevity and increase stress resistance by activating transcription factors Msn2/Msn4 and Sod2 [12855292]. SCH9 deletion mutants exhibit more than 3-fold extension of chronological lifespan. By day 9 of medium depletion all the wild-type cells were dead while 50% sch9 mutants survived [17710147]. Deletion of SCH9 also increases resistance to heat shock and oxidative stress [11292860], and increases replicative lifespan by 18% (in DBY746) [12586694]. SCH9 deletion increases the replicative lifespan by 40% in the alpha strain [18340043] and increases mean chronological lifespan by 97 - 246% (97, 133, 154, 226, 246) in diploid cells [21447998]. Mutation or deletion of SCH9 increases resistance to oxidants and extends chronological lifespan [11292860; 16286010]. The extended lifespan of SCH9 deletion mutants is not further extended by low glucose DR and is independent of Sir2 [16293764]. Deletion of RIM15 or GIS1 reverses chronological lifespan extension associated with sch9Delta. Water restriction further increases chronological lifespan of sch9Delta [18225956]. Deletion of SCH9 results in a longer chronological lifespan [21076178]. | 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 |
| CYR1 | CYclic AMP Requirement 1 | The CDC35-1 allele of the adenylate cyclase CYR1 confers a 75% extension of replicative lifespan at 25 degree Celsius [11000115]. Transposon-mutagenized CYR1 increases resistance to oxidants and extends chronological lifespan by up to 90%. Stress-resistance transcription factors Msn2/Msn4 and protein kinase Rim15 are required for this lifespan extension [11292860]. CYR1 mutation is assumed to act as genetic DR mimetic [11000115]. The CDC35-1 allele of the adenylate cyclase CYR1 confers a 75% extension of replicative lifespan at 25 degree Celsius [11000115]. cyr1-1 mutation extends median chronological lifespan by 28-47% and is non-addative with lifespan extension conferred by overxpression of human MAPK1 [17662940]. | Budding yeast |
| CDC25 | Cell Division Cycle 25 | The CDC25-10 allele extends mean and maximum replicative lifespan by 34% and 18%, respectively, at 30 degree Celsius. cdc25-10 mutants have an extended replicative lifespan under AL. Growth on 0.5% glucose restriction does not further extend replicative lifespan of cdc25-10 mutants. CDC25 null mutant is not viable. CDC25 appears to act in the same genetic pathway as SIR2 and NPT1 and is suggested to be genetic model of DR [11000115]. | Budding yeast |
| 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 |
| SWH1 | — | SWH1 (alias OSH1) deletion mutants have an extended replicative lifespan (p=0.02) and DR does not increase the long lifespan of SWH1 deletion mutants [Xia et al. unpublished]. | 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| age-1 | AGEing alteration 1 | Recessive knockout mutants of age-1 have a 40-65% increase in mean lifespan and a 65-110% increase in maximum lifespan [8608934; 8700226]. age-1(mg44) zygotic null mutants have a mean (99%) and maximum (117%) lifespan extension [18828672]. Even in axenic culture lifespan of age-1 is extended up to 100%. age-1 mutation significantly extends lifespan under AL, but only slightly under sDR [16720740].
RNAi against age-1 extends lifespan by 30% [8700226; 8608934]. age-1 RNAi increases mean and maximum lifespan by 36-46% and 48-50% [12447374]. RNAi against age-1 increases mean lifespan by 83% [18828672].
age-1 mutants are dauer constitutive [8056303] and display lower brood size as well as increased embryonic lethality [9504918]. Additionally, age-1 mutants have elevated levels of superoxidase dismutase and catalase activities [8389142]. age-1 RNAi and mutation extend lifespan by 30% and 100%, respectively [8700226; 8608934]. | 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 |
| 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 |
| 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 |
| pka1 | cAMP-dependent protein kinase 1 | pka1 knockouts exhibits a three-fold increase in chronological lifespan with up to 187% longer maximum lifespan [16822282]. Deleting ser/thr cAMP-activated protein kinase pka1 extends chronological lifespan under normal condition, but there is no additive effect with DR [20075862]. | Fission yeast |
| p53 | — | Overexpression of wild-type p53 during adult life has no significant effect on lifespan. Expression of dominant-negative versions of p53 in adult neurons extends lifespan by 58% in females and by 32% in males and increases resistance to genotoxic stress and resistance to oxidative stress, but not to starvation or heat stress, while not affecting egg production or physical activity.
Dominant negative p53 expression cancels out lifespan extension effect of DR, low calorie-food (5% SY). Muscle or fat body specific expression of a dominant negative form of p53 as well as globally lack of p53 decreases lifespan [16303568]. Loss of p53 activity slightly shortens the lifespan. Mutants that lack p53 survive well up to 50 days, but mortality rate increases relative to wild-type at later ages. p53 mutant animals are extremely sensitive to irradiation [12935877].
Expression of dominant-negative (DN) form of p53 in adult neurons, but not in muscle or fat body cells, extends median lifespan by 19% and maximum lifespan by 8%. The lifespan of dietary-restricted flies is not further extended by simultaneously expressing DN-DMp53 in the nervous system, indicating that a decrease in Dmp53 activity may be part of the DR lifespan-extending effect. Selective expression of DN-Dmp53 in only the 14 insulin-producing cell (IPCs) in the brain extends lifespan to the same extent as expression in all neurons and this lifespan extension is not additive with DR [17686972].
| Fruit fly |
