| 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 |
| IL6 | interleukin 6 (interferon, beta 2) | — | Human |
| IDP3 | Isocitrate Dehydrogenase, NADP-specific 3 | Deletion of IDP3 results in a replicative lifespan increase by 15% in the alpha strain and decrease by 20% in the a strain [18340043; 19030232]. | Budding yeast |
| 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 |
| KLF14 | Kruppel-like factor 14 | Six aging differentially methylated markers lay within KLF14 [23177740]. | Human |
| let-4 | LEThal 4 | let-4 (alias sym-5) is downregulated in space.
RNA intereference of let-4 extends mean and 75%ile lifespan by 4%, but reduces maximum lifespan by 25% [22768380]. | Nematode |
| Lamp2a | lysosomal-associated membrane protein 2 | Lamp2a, the receptor for chaperone-mediate autophagy (CMA) decreases in abundance with age. Maintaining the amount of the Lamp2a (in a double transgenic mice) specifically in the liver at levels found in young adults prevents age-dependent decrease in receptor abundance at the cellular and organ levels. In this mice CMA activity is maintained until advanced ages which results in preservation of the autophagic activity and is associated with lower intracellular accumulation of damaged proteins, better ability to handle protein damage and improved organ function [19115216; 18690243]. Lamp2a expression restored not only CMA but also macrophagy and proteasomal degradation to the level observed in young liver as well as `youthful` mitochondrial function and cellular ATP abundance and overall youthful liver functions [18776878].
| House mouse |
| Mgat5 | mannoside acetylglucosaminyltransferase 5 | Although grossly normal at birth, knockout mice display multiple deficiencies with age including hypersensitivity to autoimmune disease, higher oxidative metabolism, resistance to weight-gain, and signs of early ageing such as osteoporosis, decreased muscle mass, and depletion of adult stem cells. Interestingly, Mgat5-/-Pten+/- and Mgat5+/-Pten+/- mutant mice showed a small but significant increase in lifespan when compared to Pten+/- mice, accompanied by an apparent delay in the inevitable development of cancer in Pten+/- mice. | House mouse |
| mdt-26 | MeDiaTor 26 | RNA interference of mdt-26 decreases the median lifespan 42% in daf-2 long-lived mutants [18006689]. | Nematode |
| 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 |
| miR-214 | microRNA 214 | Expression increases with age in mouse liver. The miRNA downregulates detoxification and regeneration genes, which may contribute to aging [18561983]. | House mouse |
| Mir27a | MicroRNA 27a | In Ames dwarf mice (which displays delayed Aging), Mir27a expression is significantly higher than in control mice. Mir27a may be responsible for delayed Aging in dwarf mice: it suppresses the expression of ODC1 and SRM, which in turn suppresses polyamine synthesis in dwarf mice liver. Part of the ability of dwarf mice to suppress or avoid tumor or Cancer growth may be attributed to the decreased Polyamine biosynthesis. [19878148] | House mouse |
| Mir669c | microRNA 669c | Expression increases with age in mouse liver. The miRNA downregulates detoxification and regeneration genes, which may contribute to aging [18561983]. | House mouse |
| Mir34a | microRNA mir-34a | Increases in aging rat liver, which suppresses the expression of such proteins as Sirt1 and Mgst1, resulting in dysfunction of oxidative stress defense and regulation [21216258] | Norway rat |
| Mir93 | microRNA mir-93 | Increases in Aging rat Liver, which suppresses the expression of such proteins as Sirt1 and Mgst1, resulting in dysfunction of oxidative stress defense and regulation [21216258] | Norway rat |
| 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 |
| NAC | N-acetyl cysteine | Treatment with 10 mM of NAC has no effect on the lifespan of wild-type, but fully abolishes the increased longevity of nuo-6 and severly limits that of isp-1. At high concentration (> 10-15 nM) NAC can be become deleteroius even on the wild-type [21151885]. | Nematode |
| Neil1 | nei endonuclease VIII-like 1 (E. coli) | Knockout mice develop severe obesity, dyslipidemia, fatty liver disease, increased levels of DNA damage in the mtDNA, and have a tendency to develop hyperinsulinemia. | House mouse |
| 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 |
| Nos3 | nitric oxide synthase 3, endothelial cell | Knockout males exhibited premature death and age-related cardiac dysfunction but not females. | House mouse |
| NMD4 | Nonsense-Mediated mRNA Decay 4 | Deletion of NMD4 increases replicative lifespan [16293764]. NMD4 deletion results in replicative lifespan increase by 25% in the alpha strain and decrease by 20% in a strain [19030232]. | Budding yeast |
| 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 |
| Y46G5A.6 | phi-3 | RNA interference of Y46G5A.6 in adulthood shortens the extends lifespan of daf-2(mu150) mutants. Only a negligible or small reduction in the lifespan of wild-type worms occurs by knockdown of Y46G5A.6 [17392428]. | Nematode |
| INP54 | Phosphatidylinositol 4,5-bisphosphate 5-phosphatase with a role in secretion, localizes to the endoplasmic reticulum via the C-terminal tail; lacks the Sac1 domain and proline-rich region found in the other 3 INP proteins | Replicative lifespan increased by 15% in the alpha strain and decreased by 15% in the a strain | Budding yeast |
| 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 |
