GMC2 deletion | Deletion of GMC2 decreases replicative lifespan by 50% in the alpha strain [19030232]. | Yeast | -50 | — | — |
YNR066C deletion | Deletion of YNR066C decrease replicative lifespan by 50% in the alpha strain [19030232]. | Yeast | -50 | — | — |
NPT1 deletion | NPT1 deletion decreases replicative lifespan by 50% [17482543] as well as chronological lifespan [17110466]. Deletion of NPT1 shortens the lifespan in W303R. Replicative lifespan extension of cdc25-10 mutation (assumed to act as a genetic DR-mimetic) is cancelled out by NPT1 deletion [11000115].
NPT1 mutation results in loss of telomere and rDNA silencing [10841563], an effect that is likely caused by a loss of SIR2 activty due to decreased NAD levels. Mutation of NPT1 is synthetical lethal with mutation of QPT1 [11000115]. | Yeast | -50 | — | — |
Homozygous Gh1 anti-sense transgene | Animals carrying two copies of a Gh1 anti-sense transgene (tg/tg) have a slighlty shorter lifespan (by 5-10%) compared to -/- animals. tg/tg animals are dwarfs and exhibit reduced levels of serum IGF1 [12057928]. | Rat | -5 to -10 | — | — |
ucp-4 overexpression | Overexpression reduces mean lifespan by 5%, has no significant effect on median lifespan, and slighlty increases maximum lifespan by 12% [22737090]. | Worm | -5 | — | +12 |
snap-29 RNAi | RNAi against snap-29 starting in the adulthood decreases mean and maximum lifespan by 49 and 72%, respectively [23144747]. | Worm | -48.6 | — | -72.0 |
lt mutation | Loss-of-function mutation reduces mean lifespan by 47% and maximum lifespan by 10% [17435236]. | Fly | -47 | — | -10 |
NMT1 mutation | nmt1-451D allele shortens mean and maximum replicative lifespan by 47 and 44% at 24 degree Celsius (permessive temperature). Mutants have decreased resistance to acute and gradual nutrient deprivation, even at the permissive temperature [10921902]. A NMT null mutant is lethal. | Yeast | -47 | — | -44 |
YME1 deletion | Deletion of YME1 decreases chronological lifespan by 50% [17492370] as well as replicative lifespan by 45% in the alpha strain [18340043]. | Yeast | -45 to -50 | — | — |
ry mutation | Loss-of-function mutation of ry reduces mean lifespan by 45% and maximum lifespan by 35% [17435236]. | Fly | -45 | — | -35 |
bar-1 mutation | BAR-1 may play a role in regulating daf-16 during dauer formation, particularly in conditions of oxidative stress as it directly interaction with DAF-16 and loss of bar-1 reduces activity of DAF-16 in dauer formation and lifespan. Deletion of bar-1 reduces mean (44%) and maximal (18%) lifespan, which is to a similar degree as seen to daf-16 mutants [15905404]. | Worm | -44 | — | -18 |
cm mutation | Loss-of-function mutation in cm reduces mean lifespan by 43 - 53% and maximum lifespan by 40 - 44% [17435236]. | Fly | -43 to -53 | — | -40 to -44 |
ACO1 deletion | Deletion of ACO1 decreases mean chronological lifespan by 42 - 56% in diploid cells [21447998]. | Yeast | -42 to -56 | — | — |
AKR1 deletion | Deletion of AKR1 decreases replicative lifespan by 40% in the alpha strain [18340043]. Replicative lifespan decreased by 50% in the alpha strain [19030232]. | Yeast | -40 to -50 | — | — |
RAD51 deletion | Rad51 mutations result in a 40% reduced mean replicative lifespan in strain PSY316 [10207108]. RAD51 is required for gene conversion, but not for repair of an HO-induced double-stranded break [8692957]. RAD51 deletion decreases formation of extrachromosomal rDNA circles [10207108]. | — | -40 | — | — |
RIF deletion | Deletion of RIF1 decrease replicative lifespan by 40% [9275199]. RIF1 deletion increases telomere silencing and length [8319907; 1577274], and therefore likely recruits SIR2 from rDNA to the telomeres which result in lifespan shortening. The sir4-42 allele suppresses the short lifespan of a RIF1 mutant [9275199]. | — | -40 | — | — |
Hsp22 transposition | Animals that do not express Hsp22 (due to a transposition into its transcriptional starting site) have a 40% decrease in lifespan, exhibit a 30% decrease in locomotor activity and are sensitive to mild stress [20036725]. | Fly | -40 | — | — |
SOD1 deletion | Deletion of SOD1 decreases replicative lifespan by 40% [17460215]. Cells with a deletion of SOD1 exhibit a profound defect in entry into and survival during stationary phase (i.e. chronological lifespan) in the W303-B strain [8647826; 10222047], which is suppressed by expression of human Bcl-2 [9199172]. Deletion of SOD1 shortens replicative lifespan by approximately 40%. The magnitude of the decrease in lifespan does not appear to dependent on oxygen concentration in the atmosphere [12020810]. Deletion of SOD1 shortens replicative lifespan [10547026] Deletion of SOD1 shortens replicative as well as chronological lifespan [10222047].
Hypersensitivity to oxygene and significantly decreased replicative lifespan of SOD1 deletion can be ameliorated by exogenous ascorbate. If acorbate's negative effects of auto-oxidation are prevented by exchange of medium, ascorbate prolongs mean and maximum replicative lifespan in the atmosphere of air and pure oxygene [15621721].
SOD1 deletion causes sensitivity to hyperoxia as well as methionine and lysine auxotrohies [9199172]. | Yeast | -40 | — | — |
ARP1 deletion | Deletion of ARP1 decreases replicative lifespan by 40% in the alpha strain [18340043; 19030232]. | Yeast | -40 | — | — |
mir-71 mutation | Loss-of-function of mir-71 decreases lifespan [21129974]. mir-71 mutants have a reduced lifespan with 40% decrease in mean lifespan. Loss of mir-71 function suppresses the long lifespan of glp-1(e2141) mutants [22482727], | Worm | -40 | — | — |
HAP5 deletion | Deletion of HAP5 shortens replicative lifespan by approximately 40%. This is not a premature aging phenotype as "old" HAP5 cells do not become premature sterile or exhibit other biomarkers of yeast aging [9271578]. HAP5 null mutants are unable to grow on a non-fermentable carbon source [7828851]. | Yeast | -40 | — | — |
YBR225W deletion | Deletion of YBR225W decreases replicative lifespan by 40% in the alpha strain [19030232]. | Yeast | -40 | — | — |
YDC1 overexpression | YDC1 overexpression decreases chronological lifespan by 40% [19059240]. | Yeast | -40 | — | — |
Msra knockout | Msra homozygous knockouts exhibit a 40% shorter lifespan than wild-type or heterozygotes (C57BL/6J). Msra -/- mice have enhanced sensitivity to oxidative stress, accumulatehigher levels of protein cabronyls, and demonstrate and atypical walking pattern [11606777]. | Mouse | -40 | — | — |
his-46 RNAi | Knockdown of his-46 via RNAi started after the animal reached the late L4 stage decreases mean lifespan by 4% [22103665]. | Worm | -4 | — | — |