| 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 |
| Hsp70Ba | Heat-shock-protein-70Ba | Hsp70Ba overexpression reduces mean and maximum lifespan up to 30% [19420297].
hsp70 and hsp22 RNA levels are higher in long-lived than in short-lived fly lines. The HDAC inhibitor TSA causes a higher expression of hsp22 and hsp70, and strikingly influences the lifespan in both long and short-lived lines, with variable degrees (up to 25%) [15695762]. | Fruit fly |
| ICAM1 | intercellular adhesion molecule 1 | ICAM1 was found to be associated with longevity [22174011]. | Human |
| IGF2R | insulin-like growth factor 2 receptor | IGF2R was found to be associated with longevity [22406557]. | 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 |
| 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 |
| 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 |
| MIR21 | MIRN21; hsa-mir-21; miR-21; miRNA21 | MIR21 is the most highly expressed microRNA gene in octogenarians and centenarians. MIR21 expression is higher under cardiovascular diseases and lower in centenarian offspring. MIR21 is correlated with C-reactive protein and fibrinogen levels. TGF-βR2 mRNA, a MIR21 target, exhibits the highest expression in leukocytes form a subset of octogenarians. MIR-21 may be a biomarker of inflammation [23041385]. | 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 |
| NTHL1 | nth endonuclease III-like 1 (E. coli) | NTHL1 was found to be associated with longevity [22406557]. | Human |
| NTLH1 | nescient helix loop helix 1 | NTLH1 was found to be associated with longevity [22406557]. | 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 |
| CLU | clusterin | Overexpression of the secretory form of human Clusterin in fruit flies increases mean lifespan. hClu overexpression flies also have greater tolerance to heat shock, wet starvation, and oxidative stress and the whole body amounts of reactive oxygen species is lower [22465014].CLU was found to be associated with longevity [16804001]. | Fruit fly |
| PLXNA1 | plexin A1 | PLXNA1 is significantly associated with longevity [15105583]. | Human |
| POLB | polymerase (DNA directed), beta | POLB was found to be associated with longevity [22406557]. | 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 |
| PON1 | paraoxonase 1 | Polymorphism at codon 192 (Gln/Arg) of the PON1 gene was examined in 256 healthy Caucasian men (69.8 +/- 4.0 years). Gln homozygotes are more frequent in aging than Arg allele carriers [12889841].PON1 was found to be associated with longevity [15050299]. PON1 was found to be associated with longevity [15050299]. PON1 was found to be associated with longevity [17903295]. PON1 was found to be associated with longevity [12082503]. PON1 was found to be associated with longevity [12082503]. PON1 was found to be associated with longevity [12082503]. PON1 was found to be associated with longevity [16799134]. PON1 was found to be associated with longevity [16799134]. PON1 was found to be associated with longevity [15050299]. PON1 was not found to be associated with longevity [15241482]. PON1 was found to be associated with longevity [15241482]. PON1 was not found to be associated with longevity [20362697]. PON1 was not found to be associated with longevity [18034366]. | Human |
| HLA-DQB1 | major histocompatibility complex, class II, DQ beta 1 | Polymorphisms in HLA class II alleles of Okinawan centenarians were analyzed. DQB105 and DQB103 alleles were significantly increased in the centenarians [9389323].HLA-DQB1 was found to be associated with longevity [9389323]. HLA-DQB1 was not found to be associated with longevity [17714903]. | Human |
| HLA-DRB1 | major histocompatibility complex, class II, DR beta 1 | Polymorphisms in the HLA-DRB1 gene in Okinawan centenarians were analyzed. DRB1*1401 allele was significantly increased in the centenarians while DRB1*0101 and DRB1*1201 alleles were slightly decreased [9389323].HLA-DRB1 was found to be associated with longevity [9425225].HLA-DRB1 was found to be associated with longevity [9425225]. HLA-DRB1 was found to be associated with longevity [9425225]. HLA-DRB1 was found to be associated with longevity [9425225]. HLA-DRB1 was found to be associated with longevity [9389323]. HLA-DRB1 was found to be associated with longevity [12581796]. HLA-DRB1 was found to be associated with longevity [12581796]. HLA-DRB1 was found to be associated with longevity [20426625]. HLA-DRB1 was not found to be associated with longevity [16269080]. | 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 |
| RAD23B | RAD23 homolog B (S. cerevisiae) | RAD23B was found to be associated with longevity [22406557]. | Human |
| RAD52 | RAD52 homolog (S. cerevisiae) | RAD52 was found to be associated with longevity [22406557]. | Human |
| RIMBP2 | RIMS binding protein 2 | RIMBP2 was found to be associated with longevity [22174011]. | Human |
