| 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 [6608731]. | Mouse | — | — | — |
| 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 [19776219]. | Mouse | — | — | — |
| Prkar2b knockout | 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]. | Mouse | — | +0 to +14 | +0 to +14 |
| Coq7 knockout | Mice heterozygous in Coq7 live about 15 to 30% longer than controls [16195414]. | Mouse | +15 to +30 | — | — |
| 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 [17227869]. | Mouse | — | — | — |
| Msra knockout | 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]. | Mouse | -40 | — | — |
| 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 [16054100].
Sirt1-null mice do not exhibit lifespan extension upon Dietary Restriction [18335035]. | Mouse | — | — | — |
| Sirt6 knockout | Sirt6 knockout mice develop signs of premature ageing including a short lifespan [16439206].
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 [23217706].
| Mouse | — | — | — |
| Pou1f1 knockout | 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]. | Mouse | +25 to +50 | +25 to +50 | +25 to +50 |
| 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 [7493016]. 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 [8790408]. 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 [9462746]. | 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 [12368201]. 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 | — | — | — |
| 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 [10089885].
Cells from Terc(-/-) mice (G4 and upward) exhibit chromosomes lacking detectable teloemre repeats, aneuplody, and end-to-end fusions [9335332]. | Mouse | — | -26 | — |
| Whole-body Sirt1 deletion in the adulthood | Whole-body deletion of Sirt1 in the adulthood results in mice which are seemingly normal in every way. When mice were given low doses of resveratrol after Sirt1 was disabled, there were no discernible improvement in mitochondrial function or any paramenter, while mice with normal Sirt1 function given reservatrol showed dramatic increases in energy, mitochondrial biogenesis and function, AMPK activation and increased NAD+ levels in skeletal muscle. When mice lacking Sirt1 were given low doses of reserveratrol, AMPK was unaffected. When doses were significantly increased in these mice, AMPK was activated in a SIRT1-indepent manner, but still no benefit to mitochondrial function resulted [22560220]. | Mouse | — | — | — |
GenAge
GenDR
