| GHRHR | growth hormone releasing hormone receptor | GHRHR was found to be associated with longevity [22406557]. GHRHR was not found to be associated with longevity [19489743]. | Human |
| GSTM1 | glutathione S-transferase mu 1 | GSTM1 was found to be associated with longevity [9654200]. GSTM1 was found to be associated with longevity [9654200]. GSTM1 was found to be associated with longevity [16574194]. GSTM1 was not found to be associated with longevity [15195682]. | Human |
| CETP | cholesteryl ester transfer protein, plasma | Homozygousity for the I405V variant of CETP is associated with exceptional longevity and larger HDL and LDL particle sizes as well as lower prevalence of hypertension, cardivascular disease, and metabolic disease among Askenazi Jews [14559957]. CETP I405V homozygousity is associated with exceptional longevity and preservation of cognitive function in Askenazi Jews [17190939].
V/V homozygotes tend to have a 9-23% CETP deficiency [9610775; 15243211]. A decrease in CETP function increases HDL (high density lipoproteins) levels in the body, and decreases LDL (low-density lipoprotein). The result of this s that HDL-c levels are approximately equal in individuals with the I/I or I/V genotypes, while there are ten percent higher in V/V individuals [9610775].
Therefore the V/V SNP acts kind like an endogenous *CEPT inhibitor*, which might be the responsible for the increase in longevity but may also have side effects.CETP was found to be associated with longevity [22336474].CETP was found to be associated with longevity [15621216].CETP was found to be associated with longevity [15888337]. CETP was found to be associated with longevity [22234866]. CETP was found to be associated with longevity [22336474]. CETP was found to be associated with longevity [23389097]. CETP was found to be associated with longevity [23389097]. CETP was found to be associated with longevity [15621216]. CETP was found to be associated with longevity [15888337]. CETP was not found to be associated with longevity [23389097]. CETP was found to be associated with longevity [14559957]. CETP was found to be associated with longevity [16602826]. CETP was found to be associated with longevity [23162014]. CETP was not found to be associated with longevity [14559957]. CETP was found to be associated with longevity [18034366]. CETP was not found to be associated with longevity [24468472]. | 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 |
| IGSF4 | cell adhesion molecule 1 | IGSF4 was found to be associated with longevity [22279548]. IGSF4 was not found to be associated with longevity [21612516]. | Human |
| IL-6 | interleukin 6 (interferon, beta 2) | IL-6 was found to be associated with longevity [15664628]. IL-6 was found to be associated with longevity [11500818]. IL-6 was not found to be associated with longevity [15236771]. IL-6 was not found to be associated with longevity [11772517]. | Human |
| IL1A | interleukin 1, alpha | IL1A was found to be associated with longevity [12714264]. IL1A was found to be associated with longevity [11640949]. IL1A was not found to be associated with longevity [12714264]. IL1A was not found to be associated with longevity [11640949]. | Human |
| IL1B | interleukin 1, beta | IL1B was found to be associated with longevity [12714264]. IL1B was found to be associated with longevity [11640949]. IL1B was found to be associated with longevity [11640949]. IL1B was not found to be associated with longevity [12714264]. IL1B was not found to be associated with longevity [11640949]. | Human |
| IL1RN | interleukin 1 receptor antagonist | IL1RN was found to be associated with longevity [12714264]. IL1RN was found to be associated with longevity [11640949]. IL1RN was not found to be associated with longevity [12714264]. IL1RN was not found to be associated with longevity [11640949]. | Human |
| IL2 | interleukin 2 | IL2 was found to be associated with longevity [21299522]. IL2 was not found to be associated with longevity [16518704]. | Human |
| MTTP | microsomal triglyceride transfer protein | In a genome-wide scan for loci associated with exceptional longevity in 308 excpetinoal long-lived individuals (representing 17 sibships) a locus on chromosome 4 which maps to MTTP appears to be associated with long-lifespan in this group of subjects [11526246]. Siblings of centenarians are four times more likely to live into their 90s than control siblings [10326548]. Among a U.S.-based group of lon-lived individuals, there is a statistically significant under-representation of a risk allele of MTTP. These result was not replicated in a French-based longevity study, but this discrepancy could be due to a lack of statistically significance [11778046]. Howerver, another study failed to find a significant correlation between MTTP haplotype and longevity in1589 German nonagenarians, centenarians, and appropriately matched controls [15911777]. Neither the chromosomal loci nor MTTP were found to be associated with longevity in nonagenarian individuals in the Leiden Longevity study and Leiden 85-Plus Study [16611701]. Despite the lack of replication, humans homozysous for two on-functioning alleles of MTTP suffer from abetalipoproteinemia and lack of ApoB particles in serum. Also drugs that inhibit MTTP improve lipoprotein profiles.MTTP was found to be associated with longevity [16015282]. MTTP was found to be associated with longevity [17339647]. MTTP was found to be associated with longevity [16611701]. MTTP was found to be associated with longevity [16611701]. MTTP was found to be associated with longevity [16611701]. MTTP was found to be associated with longevity [16611701]. MTTP was found to be associated with longevity [16611701]. MTTP was found to be associated with longevity [16611701]. MTTP was not found to be associated with longevity [15911777]. MTTP was found to be associated with longevity [22496539]. | 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 |
| FOXO1 | forkhead box O1 | In men FOXO1A gene polymorphism (rs4943794) is possible associated with aging [22661237].FOXO1 was found to be associated with longevity [19793722]. FOXO1 was found to be associated with longevity [19793722; 19793722; 21388494]. FOXO1 was not found to be associated with longevity [18765803; 12843179]. | Human |
| GHR | growth hormone receptor | Individuals with low GH/IGF-I signaling due to a defect in the growth hormone receptor (GHR) are protected against cancer. Among the human individuals with a defect in GHR no cancer deaths were observed. GHR deficiency does not appear to extend lifespan because it is associated with increased risk of heart disease [21325617]. Variants in GHR were found to be associated with longevity [19489743]. | Human |
| IRS2 | insulin receptor substrate 2 | IRS2 was found to be associated with longevity [19887537]. IRS2 was not found to be associated with longevity [19489743]. | Human |
| KIR2DS4 | killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 4 | KIR2DS4 was found to be associated with longevity [15130674]. KIR2DS4 was found to be associated with longevity [15130674]. KIR2DS4 was not found to be associated with longevity [15130674]. | 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 |
| LPA | lipoprotein, Lp(a) | LPA was found to be associated with longevity [11269751]. LPA was not found to be associated with longevity [9622284]. | Human |
| AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | M/T235 SNP in the AGT gene was examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years) and a significant influences on survival in males were observed, with reduced hazards of death for carriers of the M235 allele [11602206].AGT was found to be associated with longevity [15621215]. AGT was found to be associated with longevity [11602206]. AGT was not found to be associated with longevity [15621215]. | Human |
| IGF1 | insulin-like growth factor 1 (somatomedin C) | Males exhibit an age-related increase in the A-allele of rs2229765 and a change in the plasma level of IGF-1, which dropped significantly after 85 years of age. In males +over 85 years, A/A homozygous individuals have the lowest plasma IGF-1 level. However, ther was no clear correlation between rs2229765 genotype and IGF-1 in females [19460140].IGF1 was found to be associated with longevity [20199671]. IGF1 was found to be associated with longevity [18761080]. IGF1 was found to be associated with longevity [18761080]. IGF1 was found to be associated with longevity [18761080]. IGF1 was not found to be associated with longevity [19489743]. | Human |
| MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | MMP9 was found to be associated with longevity [17261792]. MMP9 was not found to be associated with longevity [17261792]. | Human |
| MTHFR | methylenetetrahydrofolate reductase (NAD(P)H) | MTHFR was found to be associated with longevity [10583447]. MTHFR was found to be associated with longevity [20003469]. MTHFR was found to be associated with longevity [9106548]. MTHFR was found to be associated with longevity [15621215]. MTHFR was found to be associated with longevity [20003469]. MTHFR was not found to be associated with longevity [9105559]. | Human |
| MTP | microsomal triglyceride transfer protein | MTP was found to be associated with longevity [15911777]. MTP was found to be associated with longevity [22496539]. MTP was not found to be associated with longevity [23273182]. MTP was not found to be associated with longevity [14615589]. MTP was found to be associated with longevity [18034366]. | Human |
| TERC | telomerase RNA component | Mutations in TERC were overpresented in Ashkenazi centenarians [19915151].TERC was not found to be associated with longevity [22136229]. | Human |
| HLA-DQA1 | major histocompatibility complex, class II, DQ alpha 1 | olymorphisms in HLA class II alleles of Okinawan centenarians were analyzed. DQA10101=0104 and DQA105 alleles were significantly increased in the centenarians [9389323].HLA-DQA1 was found to be associated with longevity [9389323]. HLA-DQA1 was found to be associated with longevity [9389323]. HLA-DQA1 was not found to be associated with longevity [17714903]. | Human |
