| Homozygous knock-in of proof-reading deficient Polg | Mice with a proof-reading-deficient version of Polg display an increased amount of mtDNA mutations (by 3 to 5-fold) and signs of premature ageing including a reduced lifespan, weight loss, reduced subcutaneous fat, alopecia, kyphosis, osteoporosis, anaemia, reduced fertility, and heart enlargement. Median lifespan of homozyous Polg mutant knock-in mice is 48 months [15164064]. | Mouse | — | — | — |
| 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 | — | — | — |
| Cisd2 knockout | Cisd2 knockout shortens lifespan resulting in premature aging [19451219]. | Mouse | — | — | — |
| 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Survival among make animals lacking Rgn (alias SMP30) is 50% at 180 days compared to 100% among controls [N. Maruyama, unpublished data].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 | — | — | — |
| Bub1b mutation | Bub1b mutation decreases median lifespan by 60% (from 15 to 6 months). Bub1b mutant mice develop many phenotypes suggestive of accelerated aging, including: progressive bilateral cataracts, substantial loss of sub dermal adipose tissue, spinal kyphosis, muscle atrophy, and decreased wound healing. Moreover, there is a pronounced increase in senescent associated Beta-galactosidase expression in late generation Bub1b mutant mice, indicative of increased rate of cellular senscence. Homozyogous knockout of Bub1b results in lethality, while heterozygous animals exhibit no aging phenotypes [15208629]. | Mouse | — | -60 | — |
| Replacement of Cebpa by Cebpb | Replacing the Cebpa gene by Cebpb increases mean lifespan by about 20% [15289464]. C/ebpalpha(beta/beta) animals consume more food but weight less than controls [10982846], and have a slightly elevated body temperature (0.3-0.5 degree Celsius) [15289464]. | Mouse | +20 | — | — |
| Sirt1 knockout | Sirt1 knock-out mouse embryonic fibroblasts (MEFs) have a significant greater replicative capacity in culture. p19ARF levels are significantly reduced in Sirt1 knock-out MEFs [16054100].
Sirt1-null mice do not exhibit lifespan extension upon Dietary Restriction [18335035]. | Mouse | — | — | — |
| 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 | — | — | — |
| 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 | — | — |
| 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 | — | — |
| 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 | — | — | — |
| 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 | — |
| Top3b knockout | Homozygous disruption of Top3b results in a normal development but a shorter lifespan (by approximately 70%) accompanied by lesions in multiple organs in C57BL/6 [11331780]. | Mouse | -70 | — | — |
| Heterozyogus Trp53 truncation mutation | Mice heterozyogous for an allele of p53 that removes the 5' portion of the protein demonstrate decreased cancer, permature aging phenotypes, and shortened lifespan in the mixed inbred C57BL/6â129/Sv background. It has been proposed that the this allele of p53 results in increased activity/overexpression [11780111]. | Mouse | — | — | — |
| Trp63 knockout | Heterozygous Trp632 mutant mice have a shortened lifespan (by 21.5%) and display features of accelerated aging [16107615].
The decreased longevity in Trp63(+/-) mice is almost identical to that of Trp53(+/m) mice in which enhanced Trp53 activity provides resistance to spontaneous tumors while simultaneously accelerating aging [16107615]. Trp63(+/-) are not susceptible to spontaneous tumors [16107615]. | Mouse | -21.5 | — | — |
| p53 deletion mutation | Mice heterozyogous for an allele of p53 that removes the 5' portion of the protein demonstrate decreased cancer, permature aging phenotypes, and shortened lifespan [11780111]. | Mouse | — | — | — |
| Ercc2 mutation | Mutations in Ercc2 increases cancer incidence and appear to accelerate ageing. Homozyogus mutation of Ercc2 results in an extreme shortening (71%) of lifespan (mean lifespan = 7 months) relative to wild-type (mean lifespan = 24 months) [de Boer et al. 2002]. The shortened lifespan of the mutant mouse is accompanied by symptoms of premature aging including osteoporosis, early greying, cahexia, and infertility.
It provides a mouse model for the britte hair disorder trichothiodystrophy (TTD) as it phenotypes include britte hair, UV sensitivity, and developmental defects [9651581]. | Mouse | -71 | — | — |
| 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 | — |
| HNRNPD deletion | HNRNPD deletion leads to accelerated aging as evidenced by strinking telomere erosion, markedly increased DNA damage repsosne at telomere ends, pronounced cellular senescence and rapid premature aging that increases with successive generations [Pont et al., 2012]. | Mouse | — | — | — |
| Wrn mutation | Mice lacking the helicase domain fo the WRN ortholog exhibit many phenotypic features of Werner Syndrom, including a pro-oxidant status and a shorter mean lifespan. Mice with a deletion in the helicase domain [9789047] recapitulates most of the Werner syndrome phenotypes, including an abnormal hyaluronic acid excretion, higher reactive oxygen species levels, dyslipidemia, increased genomic instability, and cancer incidence. Wrn(Dehl/Dehl) mutant mice have a 10 - 15% decrease in their mean lifespan [12707040; 19741171]. | Mouse | -10 to -15 | — | — |
| Bub1b mutation | The median and maximum lifespan of mice with a nonsense mutation 2211insGTTA in BubR1 is significantly reduced. BubR1(+/GTTA) mice develop several aging-related phenotypes at an accelerated rate, including catarct formation, lordokyphosis, skeletal muscle wasting, impaired exercise ability, and fat loss. Further BubR1(+/GTTA) mice develop mild anaplodies and exhibit enhanced growth of carcinogen-induced tumors [Wijshake et al. 2012]. | Mouse | — | — | — |
| Arhgap1 knockout | Most Ahrgap1 knockout mice are weak and die during the neonatal period. Animals that survived have a shorter lifespan (median lifespan is 12 months) and show premature aging-like phenotypes, including a reduction in body mass, a loss of subdermal adipose tissue, lordokyphosis, and osteoporosis [17227869]. | Mouse | — | — | — |
| Atm knockout | Atm-deficient mice are viable, retarded in growth, infertile (male produce no mature sperm and female no gametes), display neurological dysfunction, and exhibit severe defects in T cell maturation while going on to develop thymomas [8917548; 8689683]. The majority of mutant mice rapidly develop thymic lymphomas and die before 4 months of age [8843194].
Cells of Atm(-/-) mice exhibit slow growth also in culture and premature senescence, telomeres are extensively shortened in multiple tissues [8689683].
Mice mutant for Atm and Terc display progressive multi-organ system compromise and features of accelerated aging [12540856]. | Mouse | — | — | — |
GenAge
GenDR
