| C3 | complement component 3 | Genetic variations in C3 are not associated with longevity in Italian [10219002]. | Human |
| C4A | complement component 4A (Rodgers blood group) | Genetic variations in C4A are not associated with longevity in Italian [10219002]. | Human |
| C4B | complement component 4B (Chido blood group) | Genetic variations in C4B are not associated with longevity in Italian [10219002]. | Human |
| CFB | complement factor B | Genetic variations in CFB are not associated with longevity in Italian [10219002]. | 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 |
| 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 |
| GHSR | growth hormone secretagogue receptor | GHSR was found to be associated with longevity [22406557]. | Human |
| Gr63a | Gustatory receptor 63a | Gr63a loss-of-function in female flies leads to 30% extended mean lifespan, increased fat deposition, and enhanced resistance to some (but not all) environmental stresses. Lifespan of males is not extended [20422037].
Overexpression of Gr63a has modest negative effect on lifespan [20422037]. | Fruit fly |
| GSR | glutathione reductase | GSR was found to be associated with longevity [22406557]. | Human |
| GstS1 | Glutathione S transferase S1 | GstS1 overexpression increases the mean lifespan by 33% [18059160]. | Fruit fly |
| Pi3K92E | Phosphatidylinositol-3-kinase | Heterozyogous mutation in Pi3K92E fails to extend lifespan [11292874] and it is recessive lethal.
Overexpression of a dominant-negative Pi3K92E (DP110) results in mutants that have impaired regeneration of the intestinal epithelium and are short lived with a reduction of the mean lifespan by 2.8% for males and 5.0% for females [20976250]. | Fruit fly |
| Nudt1 | nudix (nucleoside diphosphate linked moiety X)-type motif 1 | hMTH1-Tg mice express high levels of the hMTH1 hydrolase that degrades 8-oxoGTP and 8-oxoGTP and excludess 8-oxoguanine from both DNA and RNA.
hMTH1-overexpresing mice have significantly lower steady-state levels of 8-oxoguanine in both nuclear and mitochondrial DNA of several organs, including the brain. hMTH1 overexpression prevents the age-dependent accumulation of DNA 8-oxoguanine that occurs in the wild-type mice. These lower levels of oxidized guanines are associated with increased longevity and hMTH1-Tg animals live significantly longer than their wild-type littermates [23648059].
| House mouse |
| mle | maleless | Homozygous mutant animals (mle napts) display a shortened median lifespan and increased frailty in both males and females [18208580]. | Fruit fly |
| 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 |
| hsa-let-7f | — | hsa-let-7f is significantly upregulated in senescent human mesenchymal stem cells (hMSCs) when compared to early passage hMSC [18493317]. | Human |
| MIRC29 | microRNA 29c | hsa-miR-29c is significantly upregulated in senescent human mesenchymal stem cells (hMSCs) when compared to early passage hMSC [18493317]. | Human |
| MIR369 | microRNA 369 | hsa-miR-369-5p is significantly upregulated in senescent human mesenchymal stem cells (hMSCs) when compared to early passage hMSC [18493317]. | Human |
| MIR371A | microRNA 371a | hsa-miR-371 is significantly upregulated in senescent human mesenchymal stem cells (hMSCs) when compared to early passage hMSC [18493317]. | Human |
| MIR499 | microRNA-449 | hsa-miR-499 is significantly upregulated in senescent human mesenchymal stem cells (hMSCs) when compared to early passage hMSC [18493317]. | 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 |
| Pten | — | Increased Pten and 4E-BP activity in muscles is extends the lifespan [21111239]. | Fruit fly |
