Factors

We need to know every factor which determines lifespan.

Lifespan factors often but not always originate from defined genetic elements. They are not just genes, by definition they can be anything for which a Classifications schema can be build for that is related to the regulation of lifespan, such entities may include Single-Nucleotide Polymorphism, transcript variants, proteins and their complexes, compounds (i.e. small molecules like metabolites and drugs), etc. A factor should be based on a defined molecular entity or genomic position and been classified. It shall be highly flexible and scalable Concept.

While individual lifespan factors within each species or precise defined molecular entities will be captured within the Lifespan App, Data Entries of the Data App may summarize for instance the relevance of each factor class (e.g. homologous group; chemical derivate of related structure and properties, etc.) as well as draw overall conclusions. o

prometheus--2.jpg

  • Species: + -
  • symbol name observation species
    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
    GSR glutathione reductase GSR was found to be associated with longevity [22406557]. 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
    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
    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
    hsa-let-7b microRNA let-7b Let-7b, a member of the let-7 group, appears to be a tumor-suppressor. In acute lymphoblastic leukemia, let-7b is severely downregulated and its overexpression inhibits cancer cells growth [22918121]. In melanoma cells, the miRNA downregulates the expression of cell cycle regulators such as cyclin D1, D3, and A and Cdk4, which inhibits cell cycle progression. [18379589] 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
    MIR146B microRNA 146b miR-146a/b is significantly elevated during senescence as a compensatory response to restrain inflammation via the suppression of IL-6 and IL-8 secretion and downregulation of IRAK1 (component of IL-1 receptor signaling). Ectopic expression of miR-146a/b in primary fibroblasts suppresses IL-6 and IL-8 secretion and downregulation of IRAK1 [20148189]. Human
    MIR146A microRNA 146a miR-146a/b is significantly elevated during senescence as a compensatory response to restrain inflammation via the suppression of IL-6 and IL-8 secretion and downregulation of IRAK1 (component of IL-1 receptor signaling). Ectopic expression of miR-146a/b in primary fibroblasts suppresses IL-6 and IL-8 secretion and downregulation of IRAK1 [20148189]. Human
    MIR155 microRNA 155 mir-155 is significantly overexpressed in human breast cancer while targeting the miRNA could induce apoptosis and cell cycle arrest as well as inhibit cell growth. [18719391]. Mir155 acts by repressing socs1, a tumor suppressor. In addition, inflammatory signals may activate miR155, thus suggesting that the miRNA serves as a link between inflammation and malignancy formation [20354188]. It is also upregulated in lung cancer and acts an oncogene by targeting Apaf1 and thus reducing apoptosis rate [22996741]. Inhibition of mir-155 radiosensitizes cancer cells [22027557]. Human
    MIR29A microRNA 29a miR-29a reduces the amount of methylation and upregulates a long non-coding RNA form a region called MEG3 that is responsible for inducing apoptotic pathway. Thus reducing tumorgensis in non-malignant hepatocytes [21625215]. Human
    MIR34B microRNA 34b mir-34 family, particularly miR-34a, as downstream effectors of p53 involved in cell cycle [17656095], leads to cell cycle arrest, increased expression of Beta-galactosidase [17554337] and downregulation of E3F family target genes [17875987]. MDM2 inhibiting drug Nutlin-3, leads to p53 activation, induced up-regulation of primarily miR-34a and later miR-34b and miR-34c [18451145]. Human
    Factors are an extension of GenAge and GenDR.

    Comment on This Data Unit