| Gpx4 | Glutathione peroxidase 4 | Heterozygous knockouts have a 7% increase in median lifespan. | House mouse |
| htr1b | 5-hydroxytryptamine (serotonin) receptor 1B | Knockout mice displayed a decreased lifespan and early age-related motor decline. | House mouse |
| Igf1 | Insulin-like growth factor 1 (somatomedin C) | Cardiac specific overexpression of Igf1 results in a 23% increase in median lifespan, though no increase in maximum lifespan [17973971]. | House mouse |
| Igf1r | Insulin-like growth factor 1 receptor | 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]. | House mouse |
| Insr | Insulin receptor | Deletion of Insr specifically in adipose tissue results in a 15-18% increase in mean, median and maximum lifespan. Fat-specific insulin-receptor knockout (FIRKO) reduces fat mass and protects against age-related obesity and its subsequent metabolic abnormality, without an decrease in food intake. Both male and female FIRKO mice have an increase in mean lifespan of around 134 days (18%), with parallel increases in median and maximum lifespan. FIRKO mice consume the same amount of food on per animal basis as control littermates, but have 15-25% lower body-mass and 50-70% reduced fat mass [12543978]. Disruption of Insr in all tissues reults in neonatal lethality [8612577]. | House mouse |
| Irs1 | insulin receptor substrate 1 | Median lifespan was extended 18% in knockouts from both sexes and 32% in females. Female animals displayed signs of resistance to ageing markers in skin, bone, immune system, and motor dysfunction, in spite of mild, lifelong insulin resistance. Heterozygous animals had normal lifespans. | House mouse |
| Irs2 | insulin receptor substrate 2 | Irs2 brain-specific knockout mice were overweight, hyperinsulinemic, glucose intolerant, yet more active and lived up to 18% longer. | House mouse |
| Kl | Klotho | Klotho disruption results in infertility and signs of premature ageing such as a short lifespan, arteriosclerosis, skin atrophy, osteoporosis, and emphysema. Klotho overexpression leads to lifespan extension [9363890]. 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]. | House mouse |
| Lmna | lamin A | Homozygous mice display signs of premature ageing, including a marked reduction in growth rate and death by 4 weeks of age. | House mouse |
| Mcm2 | minichromosome maintenance deficient 2 mitotin (S. cerevisiae) | Conditional knockouts with reduced expression develop normally but lifespan is greatly reduced with most animals living 10-12 weeks accompanied by deficiencies in the proliferative cell compartments of several tissues and increased cancer incidence. | House mouse |
| Mgat5 | mannoside acetylglucosaminyltransferase 5 | Although grossly normal at birth, knockout mice display multiple deficiencies with age including hypersensitivity to autoimmune disease, higher oxidative metabolism, resistance to weight-gain, and signs of early ageing such as osteoporosis, decreased muscle mass, and depletion of adult stem cells. Interestingly, Mgat5-/-Pten+/- and Mgat5+/-Pten+/- mutant mice showed a small but significant increase in lifespan when compared to Pten+/- mice, accompanied by an apparent delay in the inevitable development of cancer in Pten+/- mice. | House mouse |
| Msh2 | mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) | About 50% of knock-out animals were dead by 8 month of age and all animals were dead by 12 month of age because of increased incidence of multiple cancers making these model as putatively progeroid. | House mouse |
| Msra | Methionine sulfoxide reductase A | 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]. | House mouse |
| Neil1 | nei endonuclease VIII-like 1 (E. coli) | Knockout mice develop severe obesity, dyslipidemia, fatty liver disease, increased levels of DNA damage in the mtDNA, and have a tendency to develop hyperinsulinemia. | House mouse |
| Nos3 | nitric oxide synthase 3, endothelial cell | Knockout males exhibited premature death and age-related cardiac dysfunction but not females. | House mouse |
| Pappa | Pregnancy-associated plasma protein A | Genetic deletion of PAPPA extended mean and maximum lifespan by 30-40% and reduced cancer incidence with no reduction in food intake or secondary endocrine abnormalities. | House mouse |
| Pawr | PRKC, apoptosis, WT1, regulator | Mice overexpressing the pro-apoptotic protein domain were resistant to tumours. Transgenic animals showed normal fertility, viability, and ageing, though they were slightly longer-lived possibly because of the cancer-resistance. | House mouse |
| Pck1 | phosphoenolpyruvate carboxykinase 1, cytosolic | Overexpression of Pck1 in skeletal muscle results in an increased number of mitochondria, markedly increase in activity, and extended lifespan by 30%. Transgenic mice ate 60% more than controls but had half the body weight and 10% of the body fat [17716967; Hakimi, Berger and Hanson, unpublished]. Pck1 overxpression leads to increased storage and utilization of fatty acids in muscle for energy purposes and mutants store up to 5-times more triglyceride in their skeletal muscle, and exhibit increased levels of physiological activity [18394430]. | House mouse |
| Pou1f1 | POU domain, class 1, transcription factor 1 (Pit1, growth hormone factor 1) | Snell dwarf mutation (Pit1dw) due to knockout of Pou1f1 results in a dramatic lifespan extension. The mean, median and maximum lifespan is increased by 40-50% for Snell dwarf (Pit1dw/Pit1dw) DW/J females, and 25-50% for dwarf DWC3F1 males and females with a compound heterozygous Pit1dw/Pit1dw-J genotype. Although, Snell dwarf (Pit1dw/Pit1dw) DW/J males exhibit aspects of delayed senescence, their median lifespan is by about 25% shorter, probably due to the affects of housing conditions [11718806]. Mice homozygous for loss-of-function mutations at Pit1 locus have a mean and maximum lifespan extension over 40%. Mutant dwJ/dw animals exhibit delays in age-dependent collagen cross-linking and in six age-senstive indices of immune system status. Pituitary transplantation into dwarf mice does not reverse the lifespan extension effect. Male Snell dwarf mice become obese and exhibit proportionately high leptin levels in old age [11371619]. | House mouse |
| Plau | Plasminogen activator, urokinase | Transgenic mice (called alphaMUPA) overexpression Plau in many brain sites (including hypothalamus) consume (20%) less food, have a reduced body weight (by 20%) and length (by 6%), reduced temperature, and a prolonged lifespan (by 20%) [9060969].
alphaMUPA mice have reduced levels of blood sugar and smaller size and birth frequency compared to parental control [9060969] as well as a reduced body weight [10638529]. | House mouse |
| Polg | Polymerase (DNA directed), gamma | 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]. | House mouse |
| Ppm1d | protein phosphatase 1D magnesium-dependent, delta isoform | Knockout mice are resistant to spontaneous tumors but show a modest reduction in lifespan and reduced body weight. | House mouse |
| Prdx1 | Peroxiredoxin 1 | 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] | House mouse |
| Prop1 | Prophet of Pit1, paired-like homeodomain transcription factor | 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 [8900272]. Ames dwarf mice are small due to retarded post-natal growth with a body size of one-third upon maturation into adulthood) [10838701; 8900272] 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 [8565826; 8900272]. Levels of IGF1 is also extreme low in Ames dwarf mice [8900272] and they maintain lower body temperature at rest and during stress, which is on average 1.6 degree Celsius lower [10497963]. df/df mice tend to be steril [14173795]. | House mouse |
| Rae1 | RAE1 RNA export 1 homolog (S. pombe) | Haploinsufficiency of Bub3 and Rae1, but not haploinsufficiency of either gene by itself, reduces lifespan by 12% and appears to accelerate ageing. | House mouse |
