| MTTP | microsomal triglyceride transfer protein | In a genome-wide scan for loci associated with exceptional longevity in 308 excpetinoal long-lived individuals (representing 17 sibships) a locus on chromosome 4 which maps to MTTP appears to be associated with long-lifespan in this group of subjects [11526246]. Siblings of centenarians are four times more likely to live into their 90s than control siblings [10326548]. Among a U.S.-based group of lon-lived individuals, there is a statistically significant under-representation of a risk allele of MTTP. These result was not replicated in a French-based longevity study, but this discrepancy could be due to a lack of statistically significance [11778046]. Howerver, another study failed to find a significant correlation between MTTP haplotype and longevity in1589 German nonagenarians, centenarians, and appropriately matched controls [15911777]. Neither the chromosomal loci nor MTTP were found to be associated with longevity in nonagenarian individuals in the Leiden Longevity study and Leiden 85-Plus Study [16611701]. Despite the lack of replication, humans homozysous for two on-functioning alleles of MTTP suffer from abetalipoproteinemia and lack of ApoB particles in serum. Also drugs that inhibit MTTP improve lipoprotein profiles.MTTP was found to be associated with longevity [16015282]. MTTP was found to be associated with longevity [17339647]. MTTP was found to be associated with longevity [16611701]. MTTP was found to be associated with longevity [16611701]. MTTP was found to be associated with longevity [16611701]. MTTP was found to be associated with longevity [16611701]. MTTP was found to be associated with longevity [16611701]. MTTP was found to be associated with longevity [16611701]. MTTP was not found to be associated with longevity [15911777]. MTTP was found to be associated with longevity [22496539]. | Human |
| MORF4 | mortality factor 4 | Overexpression of MORF4 reverses the immortal phenotype of immortal cell lines in complementation group B [9891081]. Cellular senescence is dominant over immortality in fused hybrids of normal and immortal human cell in culture [6879195]. Fusion of immortal cell lines with each other led to the idenetification of four complementation groups for immortality [3413074]. MORF4 rescues the immortal phenotype [9891081]. | Human |
| NR3C1 | nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) | The ER22/23EK variant of NR3C1 is correlated with longevity as well as relative gluccoritcoid resistance, greater insulin sensitivity, and lower total and low-density lipoprotein cholesterol levels in males [15276593].NR3C1 was found to be associated with longevity [22279548]. | 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 |
| 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 |
| SIRT3 | sirtuin 3 (silent mating type information regulation 2, homolog) 3 (S. cerevisiae) | The TT genotype of a silent G/T transition (G477T) in the SIRT3 gene was found to be correlated with longevity in males (but not females) in a study of individuals from Calabria, Italy [14580859]. | 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 |
| 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 |
| MIR34A | microRNA 34a | 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 |
| 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 |
| MIR34C | microRNA 34c | — | 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 |
| 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 |
| MIRC29 | microRNA 29c | hsa-miR-29c 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 |
| hsa-let-7f | — | hsa-let-7f is significantly upregulated in senescent human mesenchymal stem cells (hMSCs) when compared to early passage hMSC [18493317]. | Human |
| MIR217 | microRNA 217 | MIR217 (alias hsa-miR-217) is significantly upregulated in senescent human mesenchymal stem cells (hMSCs) when compared to early passage hMSC, but overall had very low expression levels [18493317]. | Human |
| MIR372 | microRNA 372 | miR-372 expression is able to bypass RAS-induced senescence in presence of wild-type p53 [16564011]. | Human |
| MIR373 | microRNA 373 | miR-373 expression is able to bypass RAS-induced senescence in presence of wild-type p53 [16564011]. | 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 |
| 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 |
| MAPK1 | mitogen-activated protein kinase 1 | Overexpression of human MAPK1 (alias ERK2) confers resistance to heat shock and oxidative stress extends median chronological lifespan by 24% and was statistically non-addative with cyr1-1 mutation [17662940].MAPK1 was not found to be associated with longevity [23020224]. MAPK1 was found to be associated with longevity [23020224]. | 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 |
| SOD2 | superoxide dismutase 2, mitochondrial | The SOD2 rs2758331 has been correlated with exceptional longevity in a plethora of genetic signatures [22279548].SOD2 was found to be associated with longevity [20003469]. SOD2 was found to be associated with longevity [17903295]. SOD2 was found to be associated with longevity [15621215]. SOD2 was found to be associated with longevity [20003469]. SOD2 was found to be associated with longevity [19428448]. SOD2 was not found to be associated with longevity [9887369]. SOD2 was found to be associated with longevity [22279548]. SOD2 was not found to be associated with longevity [24163049]. | 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 |
