| 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 |
| Igf2 | insulin-like growth factor 2 | Altered imprinting of Igf2 does not affect longevity [20550518]. | 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 |
| Interleukin 6 | IL-6 | — | 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 |
| Klf10 | Kruppel-like factor 10 | Klf10 is circadian, induced by glucose, binds and represses Arntl promoter. Klf10 RNAi caused cellular period shortening (of Arntl- and Per2-luc) [20070857]. | House mouse |
| Lamp2a | lysosomal-associated membrane protein 2 | Lamp2a, the receptor for chaperone-mediate autophagy (CMA) decreases in abundance with age. Maintaining the amount of the Lamp2a (in a double transgenic mice) specifically in the liver at levels found in young adults prevents age-dependent decrease in receptor abundance at the cellular and organ levels. In this mice CMA activity is maintained until advanced ages which results in preservation of the autophagic activity and is associated with lower intracellular accumulation of damaged proteins, better ability to handle protein damage and improved organ function [19115216; 18690243]. Lamp2a expression restored not only CMA but also macrophagy and proteasomal degradation to the level observed in young liver as well as `youthful` mitochondrial function and cellular ATP abundance and overall youthful liver functions [18776878].
| House mouse |
| Lep | leptin | Lep knockout results in ob/ob mice which eats excessively and becomes profoundly obese. ob/ob mice live shorter on ad libitum, but achieve a lifespan similiar to control levels under DR, yet their precentage of body fat is much greater that that of controls [6608731]. | 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 |
| miR-214 | microRNA 214 | Expression increases with age in mouse liver. The miRNA downregulates detoxification and regeneration genes, which may contribute to aging [18561983]. | House mouse |
| Mir1 | — | miR-1 is associated with stem cell differentiation in mouse and human ESCs [18371447]. | House mouse |
| Mir133 | — | miR-133 is associated with stem cell differentiation in mouse and human ESCs [18371447]. | House mouse |
| MIR20A | microRNA 20a | Overexpression of MiR-20a in mouse embryonic fibroblasts induces senescence by lowering Lrf (a transcriptional repressor of the Mdm2 inhibitor p19ARF [15662416; 9529248]) protein levels and in turn increasing p19ARF levels [18596985]. | House mouse |
| Mir27a | MicroRNA 27a | In Ames dwarf mice (which displays delayed Aging), Mir27a expression is significantly higher than in control mice. Mir27a may be responsible for delayed Aging in dwarf mice: it suppresses the expression of ODC1 and SRM, which in turn suppresses polyamine synthesis in dwarf mice liver. Part of the ability of dwarf mice to suppress or avoid tumor or Cancer growth may be attributed to the decreased Polyamine biosynthesis. [19878148] | House mouse |
| Mir489 | microRNA 489 | Mir489 is maintaining adult stem cells in quiescence phase. Inhibition of miR489 is sufficient to make murine satellite muscle cells exit the quiescence phase and enter the cell cycle through downregulation of the oncogene Dek [22358842]. | House mouse |
| Mir669c | microRNA 669c | Expression increases with age in mouse liver. The miRNA downregulates detoxification and regeneration genes, which may contribute to aging [18561983]. | 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 |
| Nfkbia | nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha | Overexpression of an endothelial dominant-negatvie I?B? gene prolonged the lifespan [22302838]. | House mouse |
| Nos3 | nitric oxide synthase 3, endothelial cell | Knockout males exhibited premature death and age-related cardiac dysfunction but not females. | House mouse |
