| F7 | coagulation factor VII (serum prothrombin conversion accelerator) | Blood coagulation factor VII (FVII) R/Q353 and FVII-323ins10 SNPs were examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years). R/Q353 and FVII-323ins10 manifest significant influences on survival in males, with reduced hazards of death for carriers of the Q353 allele and the FVII-323P10 allele [11602206].F7 was found to be associated with longevity [15621215]. F7 was found to be associated with longevity [10744171]. F7 was found to be associated with longevity [10744171]. F7 was found to be associated with longevity [11602206]. | Human |
| CPB2 | carboxypeptidase B2 (plasma) | Genotypes of the CPB2 gene were studied in 2224 men and women aged 65 or older at baseline. During 10 years of follow-up, men with the -438 A/A genotype had decreased mortality due to all causes, and lived, on average, longer than men with the -438 G allele. The effects of -438 G/A in women were smaller and not statistically significant [15939070].CPB2 was found to be associated with longevity [15939070]. | Human |
| AKAP10 | A kinase (PRKA) anchor protein 10 | Male (n= 4766) and female (n = 6202) divided into young (183-9 years) and old (60 years) groups were examined for polymorphisms. A polymorphism that results in an amino acid change from Ile to Val showed the strongest correlation with age. The Val variant was associated with a statistically significant decrease in the length of the electrocardiogram PR interval. An A to G polymorphism in the 3'UTR of D-AKAP2 showed a significant decrease of the G allele in the older sample of both genders. Additionally, the I646V polymorphism was found to be significantly different between young and old in both males and females [12646697]. | 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 |
| 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 |
| 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 |
| 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 |
| PCMT1 | protein-L-isoaspartate (D-aspartate) O-methyltransferase | The distribution of genotypes in a healthy older population of Ashenazi Jewish individuals with that in a younger ethnically matched control group were compared. 65% of the healthy older population had the heterozygous genotype, greater than the 50% expected by Hardy-Weinberg equilibrium, suggesting a possible selection for having both alleles of the repair methyltransferase in successful aging [10496068].PCMT1 was found to be associated with longevity [10496068]. | Human |
| PLXNA1 | plexin A1 | PLXNA1 is significantly associated with longevity [15105583]. | 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 |
| ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | The I/D polymorphism in ACE was a examined in centenarians (n = 338) and in adults aged 20-70 years. A variant of ACE which predisposes the coronary heat disease was more frequently in centenarians with a significant increase of the homozygous genotype [8136829].
I/D polymorphism was examined in 182 women and 100 men aged >84 years and in 100 boys and 100 girls younger than 17 years. The I/I polymorphism was depleted in the elderly males but not in the elderly females. Furthermore, significant differences were observed between ACE genotypes in elderly men and elderly women [9105559].
I/D polymorphism was examined in 394 French centenarians (13% men and 87% women) and controls (238) from 20 to 70 years of age (140 men and 98 women). Both the ACE D allele and ACE D/D genotype were more frequent in centenarians in comparison with controls, without sex-related differences nor significant correlation with a cardiovascular pathology [9761238].
I/D polymorphism was examined in 424 subjects comprising 227 Uighur individuals, 108 Kazakh individuals, and 89 Han individuals. All subjects in the latter two groups ranged in age from 65 to 70 years, whereas the Uighur subjects comprised two different age groups: those ranging in age from 59 to 70 years and those ranging in age from 90 to 113 years. Within the Uighur group, frequency of the D allele was significantly higher in the group aged >90 than in the group aged <70. The overall distributions of alleles in the three groups did not differ significantly [11773214].
Alleles of ACE was found to be associated with longevity [12547486; 22456784].ACE was found to be associated with longevity [11773214]. ACE was found to be associated with longevity [16960022]. ACE was found to be associated with longevity [19502260]. ACE was found to be associated with longevity [12634288]. ACE was found to be associated with longevity [23389097]. ACE was found to be associated with longevity [12547486]. ACE was found to be associated with longevity [22456784]. ACE was found to be associated with longevity [14528043]. ACE was found to be associated with longevity [8136829]. ACE was found to be associated with longevity [21614448]. ACE was found to be associated with longevity [21330423]. ACE was found to be associated with longevity [19502260]. ACE was found to be associated with longevity [9105559]. ACE was found to be associated with longevity [9761238]. ACE was not found to be associated with longevity [11280044]. ACE was not found to be associated with longevity [14528043]. ACE was not found to be associated with longevity [21330423]. ACE was not found to be associated with longevity [9761238]. ACE was found to be associated with longevity [23623925]. | 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 |
| YTHDF2 | YTH domain family, member 2 | A locus associated with human longevity corresponds to (TG)n microsatellite is located in the YTHDF2 gene. 412 participants of different ages, including 137 centenarians, were genotyped. The increased homozygosity in centenarians at this locus was confirmed, and observed a concomitantly increased frequency of the most frequent allele and the corresponding homozygous genotype. The same genotype was associated with increased YTHDF2 messenger RNA levels in immortalized lymphocytes. [16799135].YTHDF2 was found to be associated with longevity [16799135]. | 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 |
| 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 |
| TOMM40 | translocase of outer mitochondrial membrane 40 homolog (yeast) | TOMM440 correlates substantial with longevity and has been associated with Alzheimer's disease [22279548].
rs4420638 at TOMM40 gene locus exhibits significant association with longevity p-value = 9.6x10^-8). Combined modeling of linkage and association shows that association of longevity with APOEepsilon4 and APOEepsilon2 alleles explain the linkage at 19q1.11-q13.32 with pvalue-0.02 and p-value=1.0x10^-5, respectively [23286790]. TOMM40 was found to be associated with longevity [21418511; 23040522; 22279548]. TOMM40 was not found to be associated with longevity [24924924]. TOMM40 was found to be associated with longevity [24924924]. | Human |
| WRN | Werner syndrome, RecQ helicase-like | Mutation in WRN causes Werner Syndrome which characteristics includes prematurely aged facies, scleroderma-like skin changes, cataracts, arteriosclerosis, subcutaneous calcification, and diabetes mellitus [McKusick et al. 1963; 5327241]. Inheritance is autosomal recessive and malignancy is frequent. THe frequency is 3 per million individuals in Japan [7460386].
Cells from a Werner heterozygote exit the cell cycle at a faster rate than do normal cells [8265666]. Loss of WRN promoter aberrant mitotic recombination [11316787].
The single nucleotide polymorphism rs1800392 in WRN has been associated with exceptional longevity in a plethora of genetic signatures [22279548]. WRN was found to be associated with longevity [10069711; 20855428; 20855428; 20855428 ;17903295; 22406557; 16405962; 16405962; 16405962; 20855428; 20855428; 20855428; 22279548]. WRN was found to be associated with longevity [24244950]. | Human |
| KL | klotho | The KL-VS allele of the klotho gene is more common in infants than in elderly individuals. Individuals homozygous for KL-VS have a 2.6-fold greater chance of dying by age 65 than individuals that are homozyogous that are homozyogous for the wild-type klotho allele [11792841]. KL was found to be associated with longevity [17903295; 22406557; 15677572]. KL was not found to be associated with longevity [18034366]. KL was found to be associated with longevity [24164579]. | Human |
| INS | insulin | Expression of human insulin under an inducible heat shock promoter increases nematode lifespan by 25% and is also able to enhance the lifespan of daf-2 mutants [11274053]. INS was found to be associated with longevity [22406557; 19367319; 17989723; 19489743]. | 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 |
| 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 |
| 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 |
| UCP2 | uncoupling protein 2 (mitochondrial, proton carrier) | Overexpression of human UCP2 in the fly nervous system extends lifespan by 10-30%. Ubiquitous overexpression is lethal [16054055]. | Human |
