|Drd4 knockout ||Drd4 knockout mice, when compared with wild-type and heterozygous mice, display a 7 - 9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment . ||Mouse ||-7 to -9.7 ||— ||— |
|Foxm1 deletion ||Deletion of Foxm1 causes age-related deterioration in liver regeneration . ||Mouse ||— ||— ||— |
|Fgf23 knockout ||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 .
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 . ||Mouse ||— ||— ||— |
|Efemp1 knockout ||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 . ||Mouse ||— ||+20 ||+30 |
|Cdkn1a knockout ||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 .
The p21(-/-) strains like the Cdkn1a(tmi/Tyj) exhibits enormous regenerative capacities as it closes ear holes similar to MRL mice [20231440; 21722344]. ||Mouse ||— ||— ||— |
|Bax knockout ||Inactivation of proapoptotic Bax extends fertile potential and minimized age-related health problems, including bone and muscle loss, excess fat deposition, alopecia, cataracts, deafness, increased anxiety, and selective attention deficit. Bax deficiency does not lead to an increase in tumor incidence. Despite the apparently increased quality of life of aging females lacing Bax, there is no significant differences in overall lifespan . ||Mouse ||— ||— ||— |
|Atr knockout ||Deletion of Atr in young adults eliminates 80-90% of proliferating cells and results in several age-related phenotypes accompanied by a depletion of stem and progenitor cells and exhaustion of tissue renewal and homeostatic capacity .
Atr mutant mice (so called Seckle mice) exhibit high levels of replicative stress during embryogenesis, when proliferation is widespread, but this is reduced to marginal amounts in postnatal life. In spite of this decrease, adult Seckel mice display accelerated aging, which is further aggravated in the absence of p53. Seckel mice die in less than half a year, exhibit pancytopenia, cachexia and signs of premature aging, including hair graying, kyphosis, osteoporosis, accumulation of fat in the bone marrow, decreased density of hair follicles and thinner epidermis . ||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 .
Cells of Atm(-/-) mice exhibit slow growth also in culture and premature senescence, telomeres are extensively shortened in multiple tissues .
Mice mutant for Atm and Terc display progressive multi-organ system compromise and features of accelerated aging . ||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 . ||Mouse ||— ||— ||— |
|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%) .
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 . ||Mouse ||— ||+18 ||— |
|Sirt6 knockout ||Sirt6 knockout mice develop signs of premature ageing including a short lifespan .
Mice without Sirt6 have a higher risk of gastrointestinal cancers. Loss of Sirt6 increases the number, size and aggressiveness of tumors. Sirt6 loss leads to tumor formation even without activation of oncogenes. Transformed SIRT6-deficient cells exhibit increased glycolysis and tumor growth .
||Mouse ||— ||— ||— |
|Coq7 knockout ||Mice heterozygous in Coq7 live about 15 to 30% longer than controls . ||Mouse ||+15 to +30 ||— ||— |
|Lep knockout ||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 . ||Mouse ||— ||— ||— |
|Acacb knockout ||Acacb-null animals (alias Acc2-/-) exhibit upon regular diet an increase triglyceride breakdown, leaner phenotype, increased insulin sensitivity and no effect on lifespan . ||Mouse ||— ||— ||— |
|Trp63 knockout ||Heterozygous Trp632 mutant mice have a shortened lifespan (by 21.5%) and display features of accelerated aging .
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 . Trp63(+/-) are not susceptible to spontaneous tumors . ||Mouse ||-21.5 ||— ||— |
|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 . ||Mouse ||-70 ||— ||— |
|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 .
Cells from Terc(-/-) mice (G4 and upward) exhibit chromosomes lacking detectable teloemre repeats, aneuplody, and end-to-end fusions . ||Mouse ||— ||-26 ||— |
|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 . ||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 . 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 . 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 . ||Mouse ||— ||— ||— |
|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 .
Sirt1-null mice do not exhibit lifespan extension upon Dietary Restriction . ||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 . 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 ||— ||— ||— |
|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)  ||Mouse ||— ||— ||— |
|Hells mutation ||A hypomorphic deletion of helicase domains 3, 4 and part of 2, leads to expression of a C-terminal truncated Hells protein causing an extremely short lifespan. with 60% of homozyogous mutants dying after birth and remaining 40% surviving up to seven weeks (around 25 days) .
Hells disruption results in genomic hypomethylation, de-repression of silenced genes, and premature aging, characterized by decreased proliferation, increased replicative senescence, and altered expression of Bmi-1 and p16INK4a. Hells mutant exhibit significant hypoglycemia, low birth weight and growth retardation, and signs of premature aging such as greying hair and balding, reduced fat deposition, unstable gait, cachexia, and kyphosis . ||Mouse ||— ||— ||— |
|Homozygous Shc1 knockout ||Homozygous Shc1 knockout mice have an 28% increase in mean lifespan .
p66shc-/- cells are more resistant to apoptosis induced by hydrogen peroxide and UV light. p66shc-/- mice aremore restante to oxidative stress induced by paraquat . ||Mouse ||+28 ||— ||— |
|Heterozyogus Shc1 knockout ||Heterozyogus Shc1 knockout mice have an 7% increase in mean lifespan . ||Mouse ||+7 ||— ||— |