| Ctf1 | Cardiotrophin 1 | 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].
Treatment of cells with CT-1 increases SA-β-galactosidase, and apotosis and senescence makers (p53, p21 and p16), without modifying Mdm2 expression [23172930]. | House mouse |
| Dgat1 | Diacylglycerol O-acyltransferase 1 | Deficiency in Dagat1 promotes leanless and extends mean, median and oldest 10% survival by 23, 26 and 9% without limiting food intake [22291164]. | House mouse |
| Prkar2b | protein kinase, cAMP dependent regulatory, type II beta | Loss of function of Prkar2b results in mice that are lean and insulin sensitive. Both median and maximum lifespan is increased by 14%. Median lifespan is increasesd (from 884 to 1005) and 80% lifespan increased from 941 to 1073 days. There is no difference either in median or 80% lifespan in female genotypes [19536287]. | House mouse |
| Gsta4 | glutathione S-transferase, alpha 4 | Gsta4 null mice, had impaired 4-hydroxynonenal detoxification, but extended average lifespan. | House mouse |
| Trp53 | Transformation related protein 53 | 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]. Decreased activity of Trp53 results in increased cancer and decreased apoptosis. Mutant mice with activated Trp53 display enhanced resistance to spontaneous tumours and signs of premature ageing including reduced lifespan, osteoporosis, organ atrophy and a diminished stress tolerance [11780111]. However, super-p53 mice generate by a transgenic copy of a large genomic segment containing an intact and complete copy of p53 have an ehanced response to DNA damage, are significantly protected from cancer and had no indication of accelerated aging [12426394]. super-Ink4a/Arf/p53 mice have a synergic protection against cancer and delayed aging [Workshop RoSyBa 2011]. | House mouse |
| Terf2 | telomeric repeat binding factor 2 | Overexpression results in signs of premature ageing. | House mouse |
| Surf1 | surfeit gene 1 | Knockout mice displayed a prolonged lifespan of about 20%. | House mouse |
| Shc1 | SHC (Src homology 2 domain containing) transforming protein 1 | Heterozyogus and homozygous Shc1 knockout mice have an 7% and 28% increase in mean lifespan, respectively [10580504].
p66shc-/- cells are more resistant to apoptosis induced by hydrogen peroxide and UV light. p66shc-/- mice aremore restante to oxidative stress induced by paraquat [10580504]. | 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Cebpa | CCAAT/enhancer binding protein (C/EBP), alpha | 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 |
| Cdkn1a | Cyclin-dependent kinase inhibitor 1A | Deletion of Cdkna1 (alias p21) prolongs the lifespan of telomerase-deficient mice with dysfunctional telomeres and improves the repopulation capacity and self-renewal of hematopoietic stem cells [17143283].
The p21(-/-) strains like the Cdkn1a(tmi/Tyj) exhibits enormous regenerative capacities as it closes ear holes similar to MRL mice [20231440; 21722344]. | House mouse |
| Adcy5 | adenylate cyclase 5 | Adcy5 knockout mice are to cardiac stress and have an increased median lifespan of 30% as well as an increased maximal lifespan of 12%. Further, they are also protected from age-related reduced bone density and susceptibility to fractures, and reduced cardiac function [17662940]. | House mouse |
