| aak-2 constitutive active mutation | A constitutive active mutation of aak-2 is sufficient to cause increase stress resistance as well as to significantly extend lifespan. Both increased stress resistance and extended lifespan is reverted in daf-16 knockdown by RNAi [17900900]. | Worm | — | — | — |
| Sir2 mutation | A decrease in Sir2 (alias dSir2) blocks the life-extending effect of caloric reduction or rpd3 mutations [15520384]. Sir2 mutation does not reduce lifespan under AL [15520384]. | Fly | — | — | — |
| Mnt Mutation | A dMnt null allele results in flies with larger cells, increased weight, and decreased lifespan [16055719]. | Fly | — | — | — |
| TSA1 activating mutation | 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]. | Yeast | — | — | — |
| lin-14 gain-of-function mutation | A gain-of-function mutation in lin-14 decreases lifespan [16373574]. | Worm | — | — | — |
| LAG1 deletion | A gene deletion of LAG1 in haploid cells results in a pronounced increase (approximately 50%) in mean and in maximum replicative lifespan in the YPHDF-1A strain [8195187], but has no significant effect on lifespan in stains W303R or PSY316 (N. Bishop, G.Liszt, and L. Guarente, unpublished]. The LAG1 transcribed is preferentially expressed in young cells. LAG1 null mutant is viable and has no obvious phenotypes but shows delayed ER to Golgi transport when combined with DGT1 mutation [10198056] and is synthetical lethal with LAC1 deletion. | Yeast | +50 | — | +50 |
| hypomoprhic hep mutation | A hypomorphic allele of hep (hep1) laerlgy prevents lifespan extension caused by puc heterozygosity [14602080]. | Fly | — | — | — |
| Hells mutation | A hypomorphic deletion of helicase domains 3, 4 and part of 2, leads to expression of a C-terminal truncated Hells protein causing an extremely short lifespan. with 60% of homozyogous mutants dying after birth and remaining 40% surviving up to seven weeks (around 25 days) [15105378].
Hells disruption results in genomic hypomethylation, de-repression of silenced genes, and premature aging, characterized by decreased proliferation, increased replicative senescence, and altered expression of Bmi-1 and p16INK4a. Hells mutant exhibit significant hypoglycemia, low birth weight and growth retardation, and signs of premature aging such as greying hair and balding, reduced fat deposition, unstable gait, cachexia, and kyphosis [15105378]. | Mouse | — | — | — |
| lin-14 loss-of-function mutation | A loss-of-function mutation in lin-14 extends lifespan by 31% [16373574]. lin-14(n719) mutation extends mean and maximum lifespan of control animals by 20 and 67%, respectively [23097426].
The life-extending effects is dependent on daf-16 and hsf-1 [16373574]. Inactivation of lin-14 does not increase the lifespan of pash-1 mutants [23097426].
| Worm | +20 to +31 | — | +67 |
| isp-1 mutation | A missense mutation in isp-1 leads to low oxygen consumption, decreased sensitivity to reactive oxygen species, and increased mean (60%) and maximum (100%) lifespan. An isp-1;daf-2 double mutant has a lifespan that is longer than either single mutant, but the lifespan extension of the double mutant is not addative relative to each single mutant [11709184]. | Worm | +60 | — | +100 |
| hsf-1 mutation | A mutant allele of hsf-1 slightly decreases lifespan under AL, but cancels out the lifespan extension effect of bDR. hsf-1 RNAi also prevents lifespan extension by bDR. Glucose or glycerol does not shorten the lifespan of hsf-1 mutants. Glucose treatment completely suppresses the long lifespan caused by hsf-1 overexpression [19883616]. sDR extends the lifespan of hsf-1 mutant with a premature stop codon, that eliminates activation domain, and that of wild-type to a similar extent [19239417]. | Worm | — | — | — |
| nrh-49 mutation | A mutant allele, nhr(nr2041) results in a short lifespan. nhr-49 mutant animals accumulate fat, due to decreased expression of enzymes involved in fatty acid beta-oxidation [15719061]. | Worm | — | — | — |
| CKIepsilon mutation | A mutation in CKIepsilon called tau, if homozygous, shortens the circadian period (by 20%), increases metabolic rate (by 20%), and increases lifespan by 14-16% under conditions of constant darkness [12054192].
Male and female wild-type hamsters are heavier than homozygous mutants throughout the entire lifespan, and heterozygous mutants have intermediate weight [12054192]. | Hamster | +14 to +16 | — | — |
| wrn-1 mutation | A nonfunctional wrn-1 DNA helicase decreases the lifespan [23075628].
The expression of miR-124 in whole wrn-1 mutant worms is significantly reduced [23075628].
Supplementation of vitamin C normalizes the median lifespan of wnr-1 and mir-124 mutants [23075628]. | Worm | — | — | — |
| ATP2 Mutation | A temperature sensitive allele of ATP2 causes a clonal senescence phenotype resulting from the disruption of the age asymmetry between mother and daughter cells in that that daughter cells are born as old as they mother cells at 36 degree Celsius. This Mutation of valine to isoleucine at amino acid 90 does not affect growth on non-fermentable carbon source. This allele is associated with loss of mitochondrial membrane potential as well as failure to segregate functional mitochondria to daughter cells [12242224]. | Worm | — | — | — |
| aak-1 mutation | aak-1 does not appear to be required for the control of lifespan [15574588]. | Worm | — | — | — |
| aak-2 mutation | aak-2(ok524) knockout mutants have a 12% and 18% shorter mean and maximum lifespan, respectively as well as faster age-dependent accumulation of a lipofuscin-like fluorescent pigment in the intestine [15574588]. aak-2 mutation suppresses lifespan extension and delay of the decline in locomotor activity resulting from sDR [17900900]. aak-2 mutation cancels out the lifespan extension effect of sDR and PD, regardless of the concentration of bacteria or peptones. bDR significantly extends lifespan of aak-2 mutants, but to lesser extent than that of wild-type. eat-2 mutation extends the lifespan of aak-2 mutants to the same extent than that of wild-type. Resveratrol does not increase lifespan of aak-2 mutants [19239417]. daf-2(m577);aak-2(ok524) double mutant has a lifespan that is indistinguishable from those of aak-2(ok524) single mutant [15574588]. | Worm | -12 | — | -18 |
| ABP1 deletion | ABP1 deletion increases replicative lifespan by 30% in the alpha strain and decreases replicative lifespan by 20% in the a strain [18340043]. Deletion of ABP1 increases replicative lifespan by 20% in the alpha strain and decreases replicative lifespan by 20% in the a strain [19030232]. | Yeast | -20 to +30 | — | — |
| Ctf1 knockout | Absence of Ctf1 is associated with decreased arterial fibrosis, stiffness mad senescence and increased longevity. Ctf1-null mice have a decrease in arterial stiffness and decrease in levels of inflammatory, apoptotic and senescence, whereas telomere-linked and DNA repair proteins as well as antioxidant enzyme activities are increased. The median lifespan of Ctf1-null mice is increased by 5 month (18%) [23172930].
Wild-type and Ctf1-null mice exhibit an increase of senescence markers (p53, Mdm2, p21, and p16) with age but are lower in Ctf1-null mice. Ctf1-null mice have a diminished vascular NFκB signaling, lower inflammation and oxidative stress and reduced senescence. Ctf1-null mice have a 12% increase in body weight, 130% increased adiponectin levels and 51% decreased leptin concentrations [23172930]. | Mouse | — | +18 | — |
| Nlaz mutation | Absence of Nlaz, which is homologous to ApoD, results in a reduced lifespan in both sexes. Median lifespan is 30.8% and 22.5% lower in females and males, respectively. Maximum lifespan is reduced by 12% and 30% in females and males [21376794]. | Fly | — | -22.5 to -30.8 | -12 to -30 |
| TEC1 deletion | Absence of TEC1 causes a significant shortened chronological lifespan, but does not block chronological lifespan extension by rapamycin [21840851]. | Yeast | — | — | — |
| Ilp5 mutation | Abundance of Ilp5 mRNA is reduced under DR. Ilp5 null mutants have a normal lifespan under AL and a normal DR response. Ilp2 Ilp3 Ilp5 triple null mutants fail to have a normal response to DR. Their response is right shifted, with mutants being shorter-lived compared to wild-type on low but longer-lived on high yeast concentrations [20195512]. | Fly | — | — | — |
| Acacb knockout | Acacb-null animals (alias Acc2-/-) exhibit upon regular diet an increase triglyceride breakdown, leaner phenotype, increased insulin sensitivity and no effect on lifespan [17923673]. | Mouse | — | — | — |
| ACH1 deletion | ACH1 deletion cells accumulate a high amount of extracellular acetic acid and display a reduced mean and maximum chronological lifespan. Maximum lifespan is reduced by 32%. Lifespan shortening is completely abrogated by alleviating the acid stress either by a DR regimen that prevents acetic acid production or by transferring chronologically aging mutant cells to water. Deletion of ACH1 is accompanied by reactive oxygen species accumulation, severe mitochondrial damage, and an early insurgence of apoptosis [22754872]. | Yeast | — | — | -32 |
| Adcy5 knockout | Adcy5 knockout mice are to cardiac stress and have an increased median lifespan of 30% as well as an increased maximal lifespan of 12%. Further, they are also protected from age-related reduced bone density and susceptibility to fractures, and reduced cardiac function [17662940]. | Mouse | — | +30 | +12 |
GenAge
GenDR
