| Sod2 | superoxide dismutase 2, mitochondrial | 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].
Two-fold overexpression of Sod2 in young (4-6 months) and old (26-28 months) throughout the life results in decreased lipid peroxidation, increased resistance against paraquat-induced oxidative stress, and decreased age-related decline in mitochondrial ATP production, without any change on lifespan or age-related pathology [19633237].
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 cataract 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]. | House mouse |
| Gh | growth hormone 1 | Overexpression of a growth hormone antagonist (a mutated growth hormone that competes with the endogenous one) in mice has no effect on lifespan [12933651]. | House mouse |
| Acacb | acetyl-Coenzyme A carboxylase beta | Acacb-null animals (alias Acc2-/-) exhibit upon regular diet an increase triglyceride breakdown, leaner phenotype, increased insulin sensitivity and no effect on lifespan [17923673]. | House mouse |
| Igf2 | insulin-like growth factor 2 | Altered imprinting of Igf2 does not affect longevity [20550518]. | House mouse |
| — | Diabenol | In female NMRI and transgenic HER-2/neu mice supplementation of diabenol with drinking water 5 times a week since the age of 2 months, increases survival and inhibits spontaneous carcinogenesis.
In NMRI diabenol does not influence body weight gain dynamics, food and water consumption, but slowed down age-related disturbances in estrous function and increases the lifespan of all and 10% most long-living ones. Diabenol treatment in NMRI mice also inhibits spontaneous tumor incidence (mammary and lymphomas mainly) and increases mammary tumor latency. Diabenol treatment slows down age-related changes in estrous function in HER-2/neu mice, but fails to influence survival and slightly inhibited the incidence and decrease the size of mammary adenocarcinoma metastasis into the lung [15754958]. | House mouse |
| SOD1 | superoxide dismutase 1, soluble | Ubiquitous overexpression of SOD1 does not extend lifespan in mice. Homozyous transgenic mice with two- to five-fold overexpression of SOD1 in various tissues exhibit a light reduction in lifespan. Hemizygous transgenic mice, with 1.5- to 3-fold overexpression of SOD1 display no difference in lifespan compared with nontransgenic litermate controls [10719757]. Transgenic mice with a mutant SOD1 transgene develop neuronal cytoskeletal lesions resembling the human amytrophic lateral sclerosis (ALS) phenotype [8610185]. Transgenic mice overexpressing SOD1 (and having 3.1-fold higher cellular Cu,Zn SOD activity in the brain) have reduced infarct size following experimental cerebral ischemia [1763030].SOD1 was not found to be associated with longevity [24163049]. | Human |
| ABCA1 | ATP-binding cassette, sub-family A (ABC1), member 1 | The R219K SNP was examined in 256 centenarians and 190 healthy younger controls. The allelic frequency were not different between the two groups [12601526]. | Human |
| REN | renin | Polymorphic repeats in intron 7 (short and long alleles) were examined in 196 centenarians (143 females and 53 makes) and 358 controls (196 females and 162 male; 10-85 years old). No significant difference in genotype frequencies was found between centenarians and controls [9887369].REN was found to be associated with longevity [15105583]. REN was not found to be associated with longevity [9887369]. | Human |
| TLR4 | toll-like receptor 4 | The ASP299GLY ploymorphism in the TLR4 gene shows a significantly lower frequency in patients affected by myocardial infarction compared to controls, whereas centenarians exhibit a higher frequency [16803999]. TLR4 was found to be associated with longevity [16803999; 17493663].TLR4 was found to be associated with longevity [17493663]. TLR4 was not found to be associated with longevity [17493663]. | Human |
| HRAS1 | v-Ha-ras Harvey rat sarcoma viral oncogene homolog | HRAS1 was found to be associated with longevity [19367319]. HRAS1 was not found to be associated with longevity [19367319]. | Human |
| SIRT3 | sirtuin 3 | SIRT3 was found to be associated with longevity [14580859]. SIRT3 was found to be associated with longevity [15676284]. SIRT3 was found to be associated with longevity [15676284]. SIRT3 was found to be associated with longevity [19367319]. SIRT3 was found to be associated with longevity [19367319]. SIRT3 was not found to be associated with longevity [19367319]. SIRT3 was found to be associated with longevity [17989723]. SIRT3 was not found to be associated with longevity [23839864]. SIRT3 was found to be associated with longevity [23839864]. | Human |
| TH | tyrosine hydroxylase | Polymorphyc repeats in intron 1 (Short and Long alleles) of the TH gene were examined in 196 centenarians (143 females and 53 males) and 358 controls (196 females and 162 male; 10-85 years old). A significant loss of LL homozygous genotypes was found at the THO locus in male but not in female centenarians with respect to matched controls [9887369].TH was found to be associated with longevity [12297342]. TH was found to be associated with longevity [21407269]. TH was found to be associated with longevity [19367319]. TH was not found to be associated with longevity [19367319]. TH was found to be associated with longevity [11053670]. TH was found to be associated with longevity [17989723]. | Human |
| INS | insulin | INS was not found to be associated with longevity [19367319]. | Human |
| IGF2 | insulin-like growth factor 2 (somatomedin A) | A/G ApaI site SNP in the IGF2 gene was examined in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity (150 males and 74 females) and a group of 441 younger subjects (22 years). An increase in the A allele was observed in older Ashkenazi females and a highly significant increase was observed in the AA genotype in these subjects [15621215].IGF2 was found to be associated with longevity [19367319]. IGF2 was not found to be associated with longevity [19367319]. IGF2 was found to be associated with longevity [17989723]. IGF2 was found to be associated with longevity [15621215]. | Human |
| DEAF1 | deformed epidermal autoregulatory factor 1 (Drosophila) | DEAF1 was found to be associated with longevity [19367319]. DEAF1 was found to be associated with longevity [19367319]. DEAF1 was found to be associated with longevity [19367319]. DEAF1 was not found to be associated with longevity [19367319]. | Human |
| KRTAP5-6 | keratin associated protein 5-6 | KRTAP5-6 was found to be associated with longevity [19367319]. KRTAP5-6 was not found to be associated with longevity [19367319]. | Human |
| TSPAN32 | tetraspanin 32 | TSPAN32 was found to be associated with longevity [19367319]. TSPAN32 was not found to be associated with longevity [19367319]. | Human |
| TSHR | thyroid stimulating hormone receptor | Two single nucleotide in the TSHR were associated with increased TSH in both centenarians and their offspring [19837933].TSHR was found to be associated with longevity [19837933]. TSHR was not found to be associated with longevity [19837933]. | Human |
| CYP1A1 | cytochrome P450, family 1, subfamily A, polypeptide 1 | CYP1A1 was not found to be associated with longevity [15177664]. CYP1A1 was not found to be associated with longevity [15195682]. | Human |
| CYP1B1 | cytochrome P450, family 1, subfamily B, polypeptide 1 | CYP1B1 was not found to be associated with longevity [15177664]. | Human |
| GSTP1 | glutathione S-transferase pi 1 | GSTP1 was not found to be associated with longevity [15177664]. | Human |
| FVII | coagulation factor VII (serum prothrombin conversion accelerator) | FVII was not found to be associated with longevity [10744171]. | Human |
| KIR | killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 1 | KIR was not found to be associated with longevity [20426625]. | Human |
| GSTM1 | glutathione S-transferase mu 1 | GSTM1 was not found to be associated with longevity [11162685]. | Human |
| GSTT1 | glutathione S-transferase theta 1 | Deletion in the GSTT1 was examined in 94 nonagenarians and centenarians and 418 control subjects of younger age. A significant difference in the proportion of nonagenarians and centenarians homozygotes for the deletion was observed in comparison to control subjects [11162685].GSTT1 was found to be associated with longevity [11162685]. GSTT1 was found to be associated with longevity [16574194]. GSTT1 was not found to be associated with longevity [11162685]. GSTT1 was not found to be associated with longevity [15195682]. | Human |
