| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| htr1b | 5-hydroxytryptamine (serotonin) receptor 1B | Knockout mice displayed a decreased lifespan and early age-related motor decline. | House mouse |
| Gpx4 | Glutathione peroxidase 4 | Heterozygous knockouts have a 7% increase in median lifespan. | House mouse |
| Ghrhr | Growth hormone releasing hormone receptor | 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]. | House mouse |
| Ghr | Growth hormone receptor | 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]. Overexpression of a growth hormone antagonist (a mutated growth hormone that competes with the endogenous one) has no effect on lifespan [12933651]. | House mouse |
| Gh | Growth hormone | Overexpression of GH is associated wtih markedly reduced lifespan and various indices of premature aging [8100276]. Transgenic mice overexpressing bovine GH1 are bigger than controls and display signs of premature aging such as a shortened lifespan, glomerulosclerosis and glomerulonephritis, increased astrogliosis, and early onset of age-related changes in cognitive function [14583653]. | House mouse |
| Fxn | frataxin | Disruption results in reduced lifespan, increased oxidative stress, impaired respiration, and the development of hepatic tumors [16278235]. | House mouse |
| Foxm1 | Forkhead box M1 | Deletion of Foxm1 causes age-related deterioration in liver regeneration. Increased hepatocyte expression in 12-month-old (aged) transgenic mice of Foxm1b alone is sufficient to restore hepatocyte proliferation to levels found in 2-month-old (young) regenerating liver [14647066]. | House mouse |
| Fgf23 | Fibroblast growth factor 23 | Fgf23 knockouts have a short lifespan and display premature aging-like symptoms including kyphosis, muscle wasting, osteopenia, emphysema, uncoordinated movement, atherosclerosis, and atrophy of the intestinal villi, skin, thymus, and spleen [16436465].
Lack of Fgf23 activities results in extensive premature aging-like features and early mortality of Fgf-23(-/-) mice, while restoring the systemic effects of FGF-23 significantly ameliorates these phenotypes, with the resultant effect being improved growth, restored fertility, and significantly prolonged survival of double mutants [18729070]. | House mouse |
| Ercc4 | Excision repair cross-complementing rodent repair deficiency, complementation group 4 | ERCC4-ERCC1-deficient mice exhibit signs of premature aging [17183314]. | House mouse |
| Ercc2 | Excision repair cross-complementing rodent repair deficiency, complementation group 2 | 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]. | House mouse |
| Efemp1 | Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 | Efemp1 knockout mice exhibited an early onset of aging-associated phenotypes including a 20% shorted median lifespan and 30% shorter maximum lifespan, decreased body mass, lordokyphosis, reduced hair growth, and atrophy [17872905]. | House mouse |
| Coq7 | demethyl-Q 7 | Mice heterozygous in Coq7 live about 15 to 30% longer than controls [16195414]. Transgenic overexpression of mouse Coq7 reverts the extended lifespan of clk-1 mutants in C. elegans [11511092].
| House mouse |
| Chek2 | CHK2 checkpoint homolog (S. pombe) | Mice hypomorphic for Brca1 and double mutant for chk2 exhibit signs of premature ageing. | House mouse |
| Cebpb | CCAAT/enhancer binding protein (C/EBP), beta | 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]. | House mouse |
