| COQ3 deletion | Deletion of COQ3 decreases chronological lifespan and renders cells respiratory deficient and sensitive to hydrogen peroxide [12586694]. | Yeast | — | — | — |
| CPR7 deletion | Deletion of CPR7 has no effect on lifespan replicative lifespan, but increases chronological lifespan [11361336] | Yeast | — | — | — |
| CTF4 deletion | Deletion of CTF4 results in an approximately 75% reduced mean replicative lifespan [12024027]. | Yeast | — | — | — |
| CYT1 deletion | Deletion of CYT1 increases replicative lifespan by 15% in the alpha strain and decreases replicative lifespan by 20% in a strain. Deletion of CYT1 decreases replicative lifespan and cancels out replicative lifespan extension by HAP4 overexpression. Initially, it was shown that deletion of CYT1 also prevents lifespan extension by 0.5% glucose restriction [12124627], but later it was shown that either 0.5 or 0.05 % glucose restriction increases replicative lifespan of cyt1Delta cells [16311627]. | Yeast | — | — | — |
| daf-10 mutation | Loss of function mutation in daf-10 increases lifespan by 60% (in Bristol N2) [10617200]. daf-10 mutants are dauer defective, dye filling defective, octopamine deficient and have abnormal chemotaxis and osmotic avoidance. Mutants in daf-10 display abnormal sensory anatomy, especially amophidial neurons and sheath cells, and cephalic neurons. daf-10 mutant males do not mate [2428682]. | Worm | +60 | — | — |
| Prop1 knockout | Knockouts of Prop1 are dwarf (hence called the Ames dwarf mice) but live approximately 1 year longer than controls. Mean lifespan of males and females is extended by 49 and 68%, respectively Ames dwarf mice are small due to retarded post-natal growth and have primary pituitary deficiency consisting of the absence of, or extreme reduction in, anterior pituitary cells which produces growth hormone, prolactin and thyroid-stimulating hormone, and consequently a deficiency in these hormones. Levels of IGF1 is also extreme low in Ames dwarf mice [8900272]. | Mouse | +49 to +68 | — | — |
| daf-12 mutation | Mutations in daf-2 and daf-12, but not mutations in daf-12 alone, nearly quadruples lifespan [7789761]. Recessive loss of function mutation in daf-12 shortens lifespan. daf-12 activity is required for lifespan extension after germ line ablation [10360574]. daf-12 mutation suppresses the lifespan extension by mutation in daf-28 [8807293]. daf-12 mutants are dauer defective and heterochronic [7219552]. Some daf-12 alleles exhibit synthetic lethality with mutation of age-1 [8807293] or daf-12 [1732156]. | Worm | — | — | — |
| daf-18 mutation | daf-18 is required for complete dauer formation. daf-18 mutation partially suppresses the lifespan extension of age-1 and daf-2 mutants. daf-18 mutants are defective for dauer formation and form some dauer-like larvae when starved [7789761; 8601482]. | Worm | — | — | — |
| daf-19 mutation | Loss-of-function mutations in daf-19 increase lifespan up to 50% [10617200]. daf-19 mutants are dauer constitutive, dye-filling defective, and lack sensory cilia [7219552; 9475731]. | Worm | +50 | — | — |
| egl-4 mutation | Mutations in egl-4 extends lifespan by up to 55%. Lifespan extension by mutation of egl-4 is suppressed by daf-16. egl-4 mutation results in normal morphology and development, however egl-4 animals are almost twice as big as normal and have weak eff-laying defects [12571101]. | Worm | +55 | — | — |
| FOB1 deletion | Mutation in FOB1 extends replicative lifespan by 30-50% [10230397]. FOB1 mutation increases replicative lifespan by 25% in the alpha strain and by 10% in a strain [19030232]. FOB1 mutant exhibit an about 20% mean replicative lifespan increase [15722108]. Deletion of FOB1 causes extension in the short life span of the sir2 mutant by around 50% [10521401]. Mutation of the FOB1 gene slows the generation of rDNA circles and thus extends life span by approximately 30% in W303 and 50% in K2307 [10230397]. Even in cells lacking both Sir2 and Fob1, nicotinamide prevents the lifespan extension by DR [16311627]. | Yeast | — | — | — |
| GAL83 deletion | Deletion of GAL83 has no effect on replicative lifespan in S228C [10921902] and general GAL83 mutants have no obvious phenotype [10990457]. | Yeast | — | — | — |
| Ghr knockout | Ghr knockouts (the so called Laron mice) are dwarfs with significantly extended lifespan by 40-50% [12933651]. Ghr-/- mice are significantly longer lived as Ghr+/+ or Ghr+/- mice (by 40-50%) in both females and males [10875265; 19370397]. 30% DR fails to affect overall survival, average or median long-lifespan of Growth hormone receptor knockout (GHRKO) mice and increased maximal lifespan only in females. Insulin sensitivity in GHRKO mutants is greater than in wild-type and is not further increased by DR [16682650]. Intermittent fasting also fails to extend the long lifespan of GHRKO mice [19747233].
Lifespan of mice with a deletion in the Ghr gene live almost 5 years [21123740]. In C57BL/6J this mutation increases life expectancy by 16 to 26% depending on gender [12933651] and in mice of mixed genetic background the increases amounted to 36-55% [9371826]. Serum levels of GH are elevated in mutant mice [9371826] and mutants are smaller than wild-type. IGF-1 and IGFBP-3 levels are also reduced in Ghr mutant mice [10875265]. The age-associated decline in memory retention is delayed in Ghr mutants [11336996]. | Mouse | +16 to +55 | — | — |
| Ghrhr knockout | Homozygosity for the Ghrhr(lit) knockout mutation (called little mouse) lowers plasma growth hormone levels, impairs growth and increases lonegevity about 20% [11371619]. Lit homozygous animals are smaller than normal mice [1270792] and their pituitary is defective in growth hormone and prolactin [978118]. | Mouse | +20 | — | — |
| GPD1 deletion | GPD1 deletion shortens replicative lifespan by 25% and prevents lifespan extension by high osmolarity [12391171]. | Yeast | +25 | — | — |
| gro-1 mutation | Mutation in gro-1 extends lifespan extension by 29% and slows growth. Post-embryonic growth rate is greatly reduced in gro-1 mutants. gro-1 mutant exhibit increased resistance to heat-shock and tends to avoid bacterial lawn [Mutation in gro-1 extends lifespan extension by 29% and slows growth. Post-embryonic growth rate is greatly reduced in gro-1 mutants. gro-1 mutant exhibit increased resistance to heat-shock and tends to avoid bacterial lawn [8638122]. | Worm | +29 | — | — |
| 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 | — | — |
| HDA1 deletion | Deletion of HDA1 has no effect on longevity under AL, but acts synergistically with 0.1% glucose restriction to increase replicative lifespan [12213553]. Deletion of HDA1 leads to a slightly increased chronological lifespan [19801973]. Deletion of HDA1 has no effect on the wild-type lifespan in the short-lifespan of YSK771 strain, but suppresses the short-lifespan of SIR3 mutants [10512855]. Null mutation results in increased telomeric silencing and increased histone acetylation [8962081]. | Yeast | — | — | — |
| 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 | — | — | — |
| 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 | — | — |
| HSC82 deletion | Deletion of HSC82 has no effect on replicative lifespan, but shortens chronological lifespan [11361336]. | Yeast | — | — | — |
| HSP104 deletion | Deletion of HSP104 leads to a 14% [9851879] to 40% [17908928] reduction in mean replicative lifespan, therfore it is required for required for longevity. Exposure of cells to transient sub-lethal heat-stress extends mean lifespan by 12% while decreasing maximum lifespan by 14%. This effect does not occur in an HSP104 null mutant [9851879]. HSP104 null mutant is viable but displays reduced high temperature survival [8643570]. | Yeast | -14 to -40 | — | — |
| Igf1r knockout | Homozygous null mutation of Igf1r is lethal at birth [8402901]. Mice heterozygous for IGF1R live 26% longer. Female Igf1r(+/-) mice have 33% longer mean lifespan, whereas male mice exhibit an increase in mean lifespan of 16% (not statistically significant). Long-lived Igf1r+/- mice do not develop dwarfism, have normal energy metabolism, food and water intake, unaffected nutrient uptake, physical activity, glucose regulation, serum insulin and glucose, fertility and reproduction [12483226]. Heterozygous Igf1r mutants are more resistant to paraquat and mouse embryonic fibroblasts derived from them are more resistant to hydrogen peroxide [8402901]. | Mouse | +16 to 33 | — | — |
| 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 | — | — | — |
GenAge
GenDR
