| Chromosome 4 | epithelial cell adhesion molecule | — | Human |
| IL6 | interleukin 6 (interferon, beta 2) | — | Human |
| EXO1 | exonuclease 1 | The rs1776180 C allele in the promoter of EXO1 is significantly enriched in female Germans centenarians and this can be replicated in 445 female French centenarians. The C allele leads to the loss of binding site for the basic helix-loop-helix transcription factor E47, resulting in higher EXO1 expression [19698732].EXO1 was found to be associated with longevity [19698732]. EXO1 was not found to be associated with longevity [23770741]. | Human |
| CCL2 | chemokine (C-C motif) ligand 2 | CCL2 levels in plasma increase with age and it is part of the senescence-associated secretory phenotype [19648977]. | Human |
| CCL11 | chemokine (C-C motif) ligand 11 | CCL11 exhibits an age-related increase in the plasma and cerebrospinal fluid from healthy human individuals between 20 and 90 years [21886162]. | Human |
| BUB1B | budding uninhibited by benzimidazoles 1 homolog beta (yeast) | Mutations in BUB1B are associated with mosaic variegated aneuplody, a rare human syndrome characterized by aneuplodization, tumour predisposition and several progeroid traits, including short lifespan, growth and mental retardation, cataracts and facial dysmorphisms [16411201; 15475955; 20651707]. | 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 |
| ELOVL2 | elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 2 | In breast, kidney and lung tissues the makers cg23606718 and cg16867657 were commonly differentially methylated with age and both have been annotated to ELOVL2 [23177740], which is linked to photoaging response in human skin [20514327]. | Human |
| GTPBP10 | GTP-binding protein 10 (putative) | Age-related differential methylation of the genetic marker rs42663, which is missense mutation in GTPBP10 is statistically significant association with age and aging rate. GTPB10 associates with cg27367526 in STEAP2 [23177740]. | Human |
| JAKMIP3 | Janus kinase and microtubule interacting protein 3 | Age-related differential methylation of the genetic marker rs2818384 which is synonymous to the mutation in JAKMIP3 is statistically significant association with age and aging rate. JAKMIP3 has a *cis* association with the aging differential methylated marker cg05652533 [23177740].
Copy-number variants of JAKMIP3 are associated with glioblastoma [Xiong et al. 2010].
Xiong, M., Dong, H., Siu, H., Peng, G., Wang, Y., and Jin, L. (2010). Genome-Wide Association Studies of Copy Number Variation in Glioblastoma. Proceedings of the 4th International Conference on Bioinformatics and Biomedical Engineering (iCBBE), 1–4.
| Human |
| NEK4 | NIMA (never in mitosis gene a)-related kinase 4 | Age-related differential methylation of the genetic marker rs2230534 which is synonymous to the mutation in NEK4 is statistically significant association with age and aging rate [23177740]. | Human |
| KLF14 | Kruppel-like factor 14 | Six aging differentially methylated markers lay within KLF14 [23177740]. | Human |
| SST | Somastatin | Two with age-related differential methylation markers lay within Somastatin (SST) [23177740] which declines with age and is linked to Alzheimer's disease [15778722]. | Human |
| MDB4 | methyl-CpG binding domain protein 4 | Methylation marker cg27193080 is significantly associated with age and its methylation fraction is influenced by the SNP variantrs140692. Both the SNP and the methylation marker map to the MBD4, with the SNP in an intron and the methylation marker just upstream of the coding region [23177740]. | 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 |
| IL6 | interleukin 6 (interferon, beta 2) | Elevated IL-6 serum levels are associated with diseases, disability and mortality in the elderly. The proportion of homozyogtes for the G allele at -174 locus (a promoter genetic variability) decreases centenarian males, but not centenarians females. Only males, homozygous for the G allele at -174 locus have higher IL6- serum levels. Individuals who are genetically predisposed to produce high levels of IL-6 during aging (i.e. -174 locus GG homozygous men) are disadvantaged for longevity [11500818]. | 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 |
| 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 |
| UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCHL1 is assoicated with Parkinson's disease [9774100]. UCHL1 belongs to a family of de-ubiquitinating enzymes responsible for the hydrolysis of bonds between ubiquitin molecules and small adducts [11084366]. Decreased activity due to mutation may result in decreased labeling of abnormal proteins for clearance. | Human |
| PSEN1 | presenilin 1 | Mutations (more than 60 different) in PSEN1 are associated with Alzheimer's disease, of which all result in increased production of abnormally long amyloid beta-protein and an increase in senile plaque formation [10934557].PSEN1 was found to be associated with longevity [17903295]. | Human |
| PARK2 | parkinson protein 2, E3 ubiquitin protein ligase (parkin) | Parkin loss of function (e.g. due to deletion or point mutations) results in autosomal recessive juvenile parkinsonism, a form of Parkinson's disease with age of onset below 40 years. Associated phenotypes include resting tremor, rigidity, bradykinesia and postural instability is associated with selective neurodegeneration of the pigmented neurons in the brain stem (substiantia nigria and locus coereus) as well as the presence of intracytoplasmic inclusion bodies (Lewy bodies) [4735177].PARK2 was found to be associated with longevity [22279548]. | Human |
| HCFC1 | host cell factor C1 (VP16-accessory protein) | HCFC1 is a cronserved protein with a predominant nuclear localisation [7876203]. The mammalian HCF-1 is involved in cell cycle progression, both at the G1/S transition and at M phase and cytokinesis [12743030 ;15200950;17612494]. It acts by binding to and regulating many different transcripts and chromatin factors and assembling appropriate protein complexes for context-dependent gene expression regulation. HCF-1 helps to recruit the activating Set1/Ash2 histone methyltransferase complex [18043729]. Mammalian HCF-1 recruits te Set1/Ash2 histone methyltransferase activating complex to E2F1 and the Sin3 histone deacetylase repressive complex to E2F4 at the appropriate time of the cell cycle, which is likely to reinforce the activating or repressive functions of the respective E2F family members [17612494]. | Human |
