| YKU70 deletion | Deletion fo YKU70 shortens lifespan, but does not accelerate the normal aging process [10521401]. YKU70 null mutants are defective for non-homologous end-joining [8754818] and for telomeric silencing [9635192]. | Yeast | — | — | — |
| YKU80 deletion | Deletion of YKU80 shortens replicative lifespan, but does not accelerate the normal aging process [10521401]. YKU80 null mutant is defective for non-homologous end-joining [8754818] and for telomere silincing [9501103; 9635192] | Yeast | — | — | — |
| HSC82 deletion | Deletion of HSC82 has no effect on replicative lifespan, but shortens chronological lifespan [11361336]. | Yeast | — | — | — |
| Klotho disruption | Klotho disruption results in infertility and signs of premature ageing such as a short lifespan, arteriosclerosis, skin atrophy, osteoporosis, and emphysema. Klotho is highly expressed in brain and kidney [10631108]. The circulating form of Klotho binds to a cell-surface receptor and represses intracellular signals of insulin and IGF1. Perturbing insulin and IGF1 alleviates the aging-like phenotypes in Klotho-deficient mice [16123266]. kl/kl mice initially develop normally but exhibit growth retardation starting at 3-4 weeks of age. Their average lifespan is 61 days (none more than 100 days). These mice gradually become inactive, with reduced stride length, atrophic genital organs, thymus atrophy, arteriosclerosis (medial calcification and intimal thickening), ectopic calcification in arterial walls, osteroposis, skin atrophy, impaired maturation of gonadal cells, emphysema, reduced growth hormone-producing cells in the pituitary gland, slight hypercalcemia, and hyperphosphatemia [9363890]. kl/kl mice have decreased insulin production and increased insulin sensitivity [11016890]. | Mouse | — | — | — |
| LAC1 deletion | Deletion of LAC1 the homolog of LAG1 [9872981] has no effect on replicative lifespan in strain W303R and PSY316 [N. Bishop, G. Liszt, and L. Guarente, unpublished]. LAC1 null mutant has no obvious growth defect [10198056], but is synthetically lethal with LAG1 mutation [9872981]. | Yeast | — | — | — |
| mec-8 mutation | Recessive loss of function allele in mec-8 extends lifespan [10617200]. mec-8 mutations are mechanosensory defective and have defective dye filling of sensory neurons [8625846]. | Worm | — | — | — |
| mes-1 mutation | mes-1(bn7) mutant animals that lack germ cells live about 60% longer than fertile mes-1(bn7) controls. This lifespan extension requires daf-16 [11799246]. Homozygous mes-1 mutant progeny from homozygous mutant mothers are sterile [1783292]. | Worm | — | — | — |
| mev-1 mutation | Loss of function in mev-1 shortens lifespan to 66% of wild-type (i.e. by 34%) and accelerates accumulation of aging-associated biomarkers such as protein carboynls and fluorescent materials. mev-1 mutants are hypersensitive to raised oxygen concentrations and their lifespan decreases dramatically as oxygen concentrations increase [9716135]. Mutation of mev-1 results in paraquat sensitivity, slow grows, and low fecundity. mev-1 mutants have a 50% reduction in superoxide dismutase activt relatively to wild-type [2233820]. | Worm | — | — | — |
| MSN2 MSN4 double mutation | Deletion of MSN2 and MSN4 extends replicative lifespan and is further extended by cyr1::mTn [14741356]. Deletion of MSN2 and MSN4 does not significantly decrease chronological lifespan under AL, but attenuates chronological lifespan extension by water starvation and 0.5% glucose restriction [18225956] as well as cancels out lifespan extension of cyr1::mTn [14741356] and decreases chronological lifespan extension of ras2 deletion mutant [12586694]. Simulatnous deletion of MSN2 and MSN4 has no effect on chronological lifespan, but prevents lifespan extension by RAS2 deletion [12586694]. msn2 msn4 has no effect on replicative lifespan in PSY316, and does not prevent lifespan extension by DR [11000115] or by high osmolarity [12391171]. | Yeast | — | — | — |
| 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 | — | — | — |
| pept-2 mutation | Deletion of pept-1 (alias opt-2 or pep-2) results in retarded development, reduced body size and extended reproductive lifespan. It also further extends (60%) the life-extension caused by daf-2 mutations [15155758].
pept-2 mutants exhibit a decrease in fat content. | Worm | — | — | — |
| Akt1 mutation | Akt1 homozygotous have a significantly decreased lifespan [11292874].
Heterozygous Akt1 animals form dwarfs [11292874]. | Fly | — | — | — |
| Homozygous Prdx1 knockout | Homozygous Prdx1 knockout mice have a lifespan significant shorter than +/+ and +/- littermates and develop severe haemolytic anaemia and several malignant cancers (starting at about 9 months of age) [12891360] | Mouse | — | — | — |
| puc mutation | Heterozygous loss-of-function mutations in puc (either pucA241.1 or pucE69) significantly extend median and maximum lifespan and increase resistance to oxidative stress. Heterzyogosity for puc only modestly extends lifespan in animals carrying a hypomorphic allele of the JNK kinase hep [14602080].
puc heterzyogotes do not differ signficantly from wild-type for body size, reproductive activity or developmental timing, but exhibit increased resistance to oxidative stress and starvation [14602080]. | Fly | — | — | — |
| rad-8 mutation | Mutation of rad-8 increases lifespan by approximately 30% at 16 degree Celsius but not at 20 degree Celsius [8169328]
rad-8 mutants are hypersensitive to UV radiation, but not X-rays or MMS [7152245] | — | — | — | — |
| RAD1 mutation | Deletion of RAD1 has no effect on replicative lifespan [10207108]. | Yeast | — | — | — |
| RAD7 deletion | Deletion of RAD7 has no effect on replicative lifespan in PSY316 [10207108].
Mutation in RAD7 results in decrease repair of the non-transcribed strand in rDNA [8604332]. | Yeast | — | — | — |
| Rgn knockout | Survival among make animals lacking Rgn (alias SMP30) is 50% at 180 days compared to 100% among controls [N. Maruyama, unpublished data].
SMP30-/- mutant mice are indstuguishibale form their SMP30+/+ littermates in terms of development and fertilization capacity [12368201]. However, -/- mice were more susceptible to liver injury after treatment with anti-FAS antibody. SMP30-/- hepatocytes cultures in vitro are more susceptible to apoptosis induced by tumor-necrosis factor (TNF-alpha) plus actinomycin D (ActD) than SMP30+/+ hepatocytes.
| Mouse | — | — | — |
| RSR1 deletion | Deletion of RSR1 (alias BUD1) shortens replicative lifespan [9789734]. | Yeast | — | — | — |
| RTG2 deletion | RTG2 is required for replicative lifespan extension associated with the retrograde response, a pathway that signals the functional status of mitochondria to the nucleus to regulate the expression of several genes [11024000]. RTG2 is not required for replicative lifespan extension by DR [11024000].
RTG2 null mutants are not petite [8422683], but display various nutrient auxotrphies and alterations of carbohydrate metabolism [7727418]. | Yeast | — | — | — |
| SIM1 deletion | Disruption of SIM1 shortens mean (87.5%), but not maximum, lifespan without causing any other gross changes in cell cycle parameter or growth characteristics [8810036].
Cells bearing deletions in CLB1-4 are unable to undergo mitosis and normally arrest in G2. SIM1 disruption in clb1-4 mutant backgrounds will allow a second round of DNA synthesis without mitosis [8574583]. sim1delta;uth1delta double mutants exhibit various defects, including binucleated cells, benomyl sensitivity, heat shock sensitivity, inability to store glycogen, sensitivity to starvation and failure of spores to germinate [10612745]. | Yeast | — | — | — |
| SLT2 deletion | Deletion of SLT2 has no effect on replicative lifespan in W303 strain [12640455].
SLT2 deletion increases rDNA silencing and rDNA recombination and decreases silencing at the telomeres and HM loci [Ray et al., 2003] as well as results in decreased phosphorylation of Sir3 [12640455]. | Yeast | — | — | — |
| Sod2 homozygous knockout | Sod2(-/-) mice are born smaller, pale and less vigorous, and die with 7-10 days. The major problems are dilated cardiomyopathy, accumulaiton of lipid in various tissues particularly liver and skeletal muscle, and metabolic acidosis [7493016]. In another strain background Sod2(-/-) mice have severe anemia, degeneration of neurons in the basal ganglia and brainstem, and progressive weakness, fatigue, and cricling behavior [8790408]. Treatment of Sod(-/-) mice with superoxide dismuate/catalase mimetics (EUK-8, EUK-134, or EUK-189) partially rescues the short lifespan (mean lifespan 14-28 days) and other phenotypes [9462746]. | Mouse | — | — | — |
| Sod2 heterozyogous knockout | Life-long reduction in MnSOD activity leads to increased levels of oxidative DNA damage and increase cancer incidience, but does not appear to affect aging. Sod2(+/-) mice that have a 50% reduction in MnSOD activity in all tissues throughout the life have increased oxidative damage as evidenced by significantly elevated levels of 8-oxo-2-deoxyguanosine in nuclear DNA (in all tissues) as well as in mitochondrial DNA (in lver and brain). Increased oxidative damage to DNA is associated with a 100% increase in tumor incidience in old Sod2(+/-) mice. However, mean and maximum lifespan of Sod2(+/-) and wild-type mice is identical. Biomarkers of aging, such as catarct formation, immune response, and formation of glycooxidation products carboxylmethyl lysine and pentosidine in skin collagen changes with age to the same extent in both wild-type and Sod2(+/-) mice.
Sod2(+/-);Gpx(-/-) animals exhibit no reduction in lifespan, despite increased levels of oxidative damage and neoplasms as well as tumorgenesis [19776219]. | Mouse | — | — | — |
| Terc deletion | Telomerase null mice exhibit age-dependent telomere shortening and shortened lifespan with succeeding generations. Median lifespan is reduced by 26% in G6 Terc(-/-) mice compared to wild-type or G1-G3 Terc(-/-) (18 months vs. 24 months). G6 Tec(-/-) display hair greying, hair loss, and ulcerative skin lesions, as well as impaired response to wound healing and hematoitopitic ablation, and an increased incidence of cancer [10089885].
Cells from Terc(-/-) mice (G4 and upward) exhibit chromosomes lacking detectable teloemre repeats, aneuplody, and end-to-end fusions [9335332]. | Mouse | — | -26 | — |
GenAge
GenDR
