| INM2 deletion | Deletion of INM2 decreases replicative lifespan by 70% in the alpha strain [19030232]. | Yeast | -70 | — | — |
| Drd4 knockout | Drd4 knockout mice, when compared with wild-type and heterozygous mice, display a 7 - 9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment [23283341]. | Mouse | -7 to -9.7 | — | — |
| pas-3 RNAi | RNA interference of pas-3 shortens mean lifespan by 7% and suppresses lifespan extension by isp-1 mutation [22829775]. | Worm | -7 | — | — |
| SdhB mutation | SdhB mutants are hypersensitive to oxygen and displays signs of premature aging, including a 66% decrease in mean lifespan and a 17% decrease in maximum lifespan [17056719]. | Fly | -66 | — | -17 |
| TPS2 deletion | Deletion of TPS2 has no effect on replicative lifespan and does not prevent lifespan extension by high osmolarity [12391171]. Deletion of TPS2 decreases intracellular trehalose concentration and shortens mean chronological lifespan by 61% (at 30 degree Celsus in BY4742) [22783207].
TPS2 is required for trehalose biosynthesis in response to osmotic stress [8444170]. | Yeast | -61 | — | — |
| SIP2 deletion | Deletion of the N-myristoylprotein SIP2 results in reduced resistance to nutrient deprivation and a 60% shorter lifespan accompanied by signs of accelerated aging such as loss of silencing from telomeres and mating loci, redistribution of Sir3 to the nucleolus, progressive sterility, nucleolar fragmentation and enlargement, and accumulation of extrachromosomal rDNA [10921902].
SIP2 deletion increases replicative lifespan by 20% in the alpha strain [19030232].
SIP1 null mutation causes increase in the intracellular ATP and NAD+ levels in both young cells (generation 0-1) and older cells (generation 4), but the increase is greater in older cells [10921902]. | — | -60 to +20 | — | — |
| RAD27 deletion | Deletion of RAD27 results in signs of premature aging and approximately 60% reduction in mean replicative lifespan [12024027]. | Yeast | -60 | — | — |
| kuk Overexpression | Overexpression of kugelkern in the adult muscle results in a 60% reduction of mean lifespan [18494863]. | Fly | -60 | — | — |
| SGS1 mutation | Deletion of SGS1 causes premature aging including a shortened replicative lifespan by approximately 60%, sterility, fragmentation of the nucleolus and redistribution of the Sir3 silencing protein from telomeres to the nucleolus [Sinclair et al, 1997]. Mutation in SGS1 shortens replicative lifespan by 30% [11290710]. Introduction of mutant allele with a point mutation (SGS1 K(706)-->A) in the RecQ helicase domain that eliminates the DNA helicase activity of Sgs1 fails to rescue the premature aging of the sgs1Delta strain, demonstrating that Sgs1 DNA helicase activity is required for a normal lifespan [11861900].
Most cell death in sgs1 mutant cells is caused by a stochastic cell cycle arrest that is associated with a large-budded terminal morpholgy [McVey et al, 2001]. Overexpression of SIR2 or deletion of FOB1 extend lifespan of only those sgs1 cells that escape this arrest [11290710; 10230397].
sgs mutants have greater rate of telomere loss than wild-type cells in the abscence of telomerase [11179234]. | Yeast | -60 | — | — |
| CLA4 deletion | Deletion of CLA4 decreases replicative lifespan by 60% in the alpha strain [18340043; 19030232]. | Yeast | -60 | — | — |
| YGR071C deletion | Deletion of YGR071C decreases replicative lifespan by 60% in the alpha strain [19030232]. | Yeast | -60 | — | — |
| gdi-1 RNAi | RNAi against gdi-1 started after the animal reaches the late L4 stage decreases mean lifespan by 6-7% [22103665]. gdi-1 RNAi decrease median lifespan by 34% in daf-2 mutants [18006689]. | Worm | -6 to -7 | — | — |
| C15H9.9 RNAi | RNAi against C15H9.9 started after the animal reaches the late L4 stage decreases mean lifespan by 6-7% [22103665]. | Worm | -6 to -7 | — | — |
| bra-1 mutation | bra-1(nk1) mutation reduces mean lifespan by 6-25% [17900898]. | Worm | -6 to -25 | — | — |
| cpf-2 RNAi | RNA interference of cpf-2 decreases mean lifespan by 6% and suppresses lifespan extension by eat-2 mutation [22829775]. | Worm | -6 | — | — |
| hk mutation | Loss of function mutation in hk decreases mean lifespan by 58 - 60% and maximum lifespan by 15 - 47% [17435236]. | Fly | -58 to -60 | — | -15 to -47 |
| VAM3 deletion | Deletion of VAM3 decreases mean replicative lifespan by 56% both on AL [19030232] and on moderate DR [18690010] (in BY4742/alpha strain). | Yeast | -56 | — | — |
| AFG3 deletion | Deletion of the mitochondrial AAA protease AFG3 increases replicative lifespan by 20% in the alpha and a strains [18340043], but decreases chronological lifespan by 37 - 51% in diploid cells [21447998].
AFG3 deletion changes mean, median and maximum lifespan by 15 to 26% 17 to 30% and -25 to +58%, respectively.
AFG3 deletion leads to reduced cytoplasmic mRNA translation and its lifespan extension is independent of Sir2 and Hac1, but requires Gcn4. AFG3 deletion further extends the lifespan of cell deficient in both SIR2 and FOB1, but fails to extend the lifespan of dietary restricted cells or cells lacking GCN4. Gcn4 protein levels are increased in afg3 mutants. The deletion of AFG3 fails to extend the replicative lifespan in the W303AR strain. AFG3 deletion does deletion extend the replicative lifespan at 15°C. | Yeast | -51 to +20 | — | — |
| YHF1 deletion | Deletion of YFH1 decreases replicative lifespan by 50% [15130665]. | Yeast | -50 | — | — |
| CCS1 deletion | Deletion of CCS1 reduces replicative lifespan by 50% [17460215]. | Yeast | -50 | — | — |
| SRS2 deletion | Deletion of SRS2 shortens mean replicative lifespan by 50% [11290710]. Overexpression of SGS1 increases maximum, but not mean lifespan of SRS2 mutants [11861900]. Deletion of SRS2 is synthetical lethal in combination with deletion of SGS1 [11290710]. | Yeast | -50 | — | — |
| RRG1 deletion | Deletion of RRG1 decreases replicative lifespan by 50% in the alpha strain [19030232]. | Yeast | -50 | — | — |
| LAG2 deletion | Deletion of LAG2 in haploid SP1 strain does not affect growth, but results in a 50% decrease in the mean and maximum replicative lifespan [8760941]. | Yeast | -50 | — | -50 |
| MPT5 deletion | Deletion of MPT5 shortens replicative lifespan by about 50% [9150138; 7859289]. MPT5 deletion decreases average chronological lifespan by 50%, which is rescued to the wild-type level by PKC1 overexpression [17172436].
MPT5 mutants are temperature sensitive [7845352], hypersensitive to mating pheromone [9154842], and null mutants exhibit increased silencing at telomeres and decreased rDNA silencing [9584615]. Deletion of MPT5 is synthetical lethal with mutation of either SWI4, SWI6, or CCR4 in an ssd1-d background [11805047]. MPT5 is required for relocalization of the SIR complex to the nucleolus in sir4-42 strain [7859289]. | Yeast | -50 | — | — |
| Cav1 knockout | Knockout mice are viable and fertile but exhibit an approximately 50% reduction in lifespan probably due to a combination of pulmonary fibrosis, pulmonary hypertension, and cardiac hypertrophy [14690422]. | Mouse | -50 | — | — |
GenAge
GenDR
