| ANKRD19 | ankyrin repeat domain 19, pseudogene | ANKRD19 was not found to be associated with longevity [21612516]. | Human |
| APBB1 | amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65) | At least one copy of the minor allele of F65 was associated with decreased risk of sporadic dementia of the Alezheimer's type as suggest by a larde epidemiological study [9799084]. Fe65 protein binds to the intracellular domain of the beta-amyloid precursor protein and may modulate the internalization of betaPP. The deletion/substitution of the minor allele occurs with the intron that interrupts the two exons encoding the betaPP binding site. Linkage of the minor allele with resistance to DAT was confirmed in another study in populations over 75 years-of-age [11065130], while epidemiological studies that did not support the linage [11436125; 11099823; 11029529] lacked representation of individuals older than 75 years-old. Any protective effect that the minor allele of Fe65 might have is probably restricted to individuals older than 75 years. | Human |
| APBB2 | amyloid beta (A4) precursor protein-binding, family B, member 2 | APBB2 was found to be associated with longevity [22279548]. | Human |
| Apo C-I | apolipoprotein C-I | Apo C-I was found to be associated with longevity [9105559]. | Human |
| APOA1 | apolipoprotein A-I | APOA1-MspI-RFLP (-75 nt from the transcription starting site) polymorphism was examined in a healthy population with 304 subjects aged 18-45 years, 267 subjects aged 46-80 years and 229 subjects aged 81-109 years (including 184 subjects, 43 males and 141 females, older than 100 years). The APOA1 allele P, which increases serum LDL-C at middle-age and is over-represented in cardiovascular diseases, tends to increase its frequency in the centenarians males [12556235].APOA1 was found to be associated with longevity [12556235]. | Human |
| APOA4 | apolipoprotein A-IV | Two restriction polymorphisms, HinfI347 (Thr347/Ser) and Fnu4HI360 (Gln360/His), and a VNTR (alleles 3, 4) at the 3 region of the APOA4 gene were examined in 71 centenarians (18 men and 53 women, 100-107 years of age, mean 102.3 years) and 100 unrelated adults (21 men and 79 women, 19-59 years of age, mean 35.7 years). The Hinf347 genotype distribution was significantly different in centenarians [9622284].APOA4 was found to be associated with longevity [9533408]. APOA4 was found to be associated with longevity [9622284]. APOA4 was not found to be associated with longevity [9622284]. APOA4 was not found to be associated with longevity [12556235]. | Human |
| APOB | apolipoprotein B (including Ag(x) antigen) | A sample of 143 centenarians and a control sample of 158 individuals were examined for polymorphism in APOB restriction fragment length (RFLP) (XbaI2488 and EcoRI4154) and variable number of tandem repeat (VNTR) (3'APOB-VNTR) polymorphisms. Neither the XbaI-RFLP nor the EcoRI-RFLP was able to discriminate between centenarians and controls, while the 3'APOB-VNTR multiallelic system revealed significant differences between the samples: the frequency of alleles with fewer than 35 repeats was lower in centenarians than in controls [9050915].apoB was found to be associated with longevity [17393087].APOB was found to be associated with longevity [15028112]. APOB was found to be associated with longevity [17393087]. APOB was not found to be associated with longevity [17393087]. APOB was found to be associated with longevity [9050915]. APOB was not found to be associated with longevity [11592926]. APOB was not found to be associated with longevity [8018664]. APOB was not found to be associated with longevity [9050915]. | Human |
| APOC1 | apolipoprotein C-I | A polymorphism in the APOC1 gene is significantly associated with longevity [21740922].APOC1 was found to be associated with longevity [21740922].APOC1 was found to be associated with longevity [21740922]. APOC1 was found to be associated with longevity [9105559]. | Human |
| APOC3 | apolipoprotein C-III | Several small nucleotide polymorphisms in the APOC3 gene were associated with longevity [8018664; 11193221; 16602826].
The Sst I polymorphism was examined in 179 Finnish centenarians. The S2 allele (Sst I restriction site present) occurred more often in the centenarians (frequency, 12.9%) than in the youngest reference population (frequency, 8.8%) [8018664]. | Human |
| APOCIII | apolipoprotein C-III | APOCIII was found to be associated with longevity [8018664]. | Human |
| APOE | apolipoprotein E | In humans APOE is located on chromosome 19. There are three common allelic variants of APOE (ε2 to ε4).
The resulting proteins are referred to as ApoE2, ApoE3 and ApoE4.
The respective proteins differ only in single amino acid, but have a dramatic influence on the life of affected humans.
The frequency of the epsilon 2 allele of ApoE is significantly increased in centenarians relative the overall control population, while the epsilon 4 allele is significantly decreased in centenarians [8136829]. Among individuals 85 years or older how had good cognition, the mortality of those that had the 2/3 genotype was half that in those who carried the epsilon 3/3 genotype and the mortality in subjects with the epsilon 3/4 genotype is twice that of those who carry the epsilon 3/3 genotype. This 4-fold variation results in 2-year difference in survival [8624216].
The epsilon 4 allele is also associated with higher cholesterol levels and cardiovascolar disease [10818513; 8624216] as well as risk factor for cognitive impariment under age 85 [8624216]. However the APOE polymorphism is not a risk factor for cognitive impairment in individuals older than 85 years [8624216].
The Polymorphism (E2, E3, and E4) was examined in a sample of 228 healthy Italian subjects (124 men and 104 women) aged 18-93, with the result that the frequency of E4 decreased with age and was not found in subjects aged 75 and older [8541369].
By Examining the common polymorphism was in 182 women and 100 men aged > 84 years and in 100 boys and 100 girls younger than 17 years (English, Cambridge) a difference between genotypes in the elderly women and the young sample was observed. However, this did not retain significance when the genotype frequencies of the young sample were adjusted to values expected from the allele frequencies on the basis of Hardy-Weinberg equilibrium and compared to observed genotypes in elderly men and women [9105559].
In a Braxiallian population the common polymorphism was examined in 70 elderly patients aged 80 years or more. No association was observed between the genotypes and longevity, though individuals with the E3E4 genotype had a mean age greater than those with the E3E3 genotype [12185856].
In a Korean population the common polymorphism examination of 103 centenarians (13 men and 90 women, mean age 102.4 +/- 2.6 years) and 6435 adults (5008 men and 1427 women) of mean age 50.7 +/- 7.9 years found that the frequencies of genotypes and alleles of the centenarians were not significantly different from those of the control groups. The frequency of the E4 allele was significantly higher in centenarians with dementia than in centenarians without definitive dementia [12634288].
Examination of the common polymorphism 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) revealed that the Ashkenazi older subjects were characterized by an increased percentage of the E2 allele and a decreased percentage of the E4 allele [15621215].
A study of APOE polymorphisms in a samples of 538 Colombian subjects (aged 18-106 years) did not find any differences between young and old subjects [16971231].
APOE correlated highly with longevity in a plethora of genetic signatures and has been associated with Alzheimer's disease [22279548].
ε3 and *ε4 are much more efficient binding lipoprotein receptors [11882522].
The various APOE isoforms interact differently with specific lipoprotein receptors, ultimately altering circulating levels of cholesterol. APOE from VLDL, chylomirons and chylomicron remnants binds to specific receptor cells in the liver. Carriers of the *ε2 allele are less efficient at making and transferring VLDLs and chylomicrons from the blood plasma to the liver because of its binding properties. By contrast, carriers of the ε3 are much more efficient in these processes. While APOE4 and APOE3 bind with approximately equal affinity to lipoprotein receptors, APOE2 binds with less than 2% of this strength [7628082]. Thus, compared with carriers of the *ε3 or *ε4 allele, carriers of the *ε2 allele are slower to clear dietary fat from their blood [3479440]. The difference lipoprotein particles results in differences in regulating hepatic low density lipoprotein (LDL) receptors which in turn contribute to genotypic differences in total and LDL cholesterol levels [1998654; 3277611; 8696954; 8018666; 1867194; 3698268].
While APOE was not found to be associated with longevity in some studies [16799145; 21703254], APOE was found to be associated with longevity in many others [11780357; 11213279; 16487435; [23286790; 15621215; 8018664; 21418511; 8136829; 9792194; 22445811; 12185856; 10069711; 21703254; 17934638; 17234815; 11788960; 17934638; 10643896; 11280044; 14615589; 23040522; 18034366]. APOE was found to be associated with longevity [22445811]. APOE was not found to be associated with longevity [24924924]. APOE was found to be associated with longevity [24924924]. APOE was found to be associated with longevity [24688116]. APOE was found to be associated with longevity [24534555]. APOE was found to be associated with longevity [24244950]. APOE was found to be associated with longevity [24126160]. | Human |
| APOE + TOMM40 | — | APOE + TOMM40 was not found to be associated with longevity [21418511]. APOE + TOMM40 was not found to be associated with longevity [23040522]. | Human |
| APOE E4 | — | — | Human |
| ARHGEF19 | Rho guanine nucleotide exchange factor (GEF) 19 | ARHGEF19 was found to be associated with longevity [22445811]. | Human |
| ART3 | ADP-ribosyltransferase 3 | ART3 was found to be associated with longevity [22445811]. | Human |
| ATCAY | ataxia, cerebellar, Cayman type | ATCAY was found to be associated with longevity [21782286]. | Human |
| ATF4 | — | ATF4 was not found to be associated with longevity [23770741]. | Human |
| ATK1 | v-akt murine thymoma viral oncogene homolog 1 | ATK1 was found to be associated with longevity [21418511]. | Human |
| ATM | ataxia telangiectasia mutated | Individuals with ataxia-telangiectasia (AT) have a decreased lifespan, with a maximum of 52 years [3864931].ATM was found to be associated with longevity [22960875].ATM was found to be associated with longevity [20816691]. ATM was found to be associated with longevity [22960875]. ATM was found to be associated with longevity [22960875]. | Human |
| ATP8 | — | ATP8 was found to be associated with longevity [10996007]. | Human |
| ATP9B | ATPase, class II, type 9B | ATP9B was found to be associated with longevity [21782286]. | Human |
| ATXN1 | ataxin 1 | ATXN1 was not found to be associated with longevity [21612516]. | Human |
| B9D2 | B9 protein domain 2 | B9D2 was not found to be associated with longevity [15569360]. | Human |
| B9D2 + TGFB1 | — | B9D2 + TGFB1 was found to be associated with longevity [15569360]. | Human |
| BAT5 | abhydrolase domain containing 16A | BAT5 was found to be associated with longevity [22279548]. | Human |
