Research Centre Information Centre AgeFactDB
Release 1 - Aug 15, 2013

Browse

Ageing Phenotype Observations List—Data Type 1

NOTE:

We distinguish between different types of ageing relevance evidence. Experimental studies on ageing factors result in observations with experimental ageing relevance evidence (1). According to our definition of ageing factors a comparison of two situations, with and without the action of the ageing factor, is required. Almost all data in AgeFactDB is of this type. There are however also a few lifespan data for populations or species included that are certainly relevant to ageing with a slightly different meaning of the term ageing relevance, however. But in this case there is no intervention study and therefore these data cannot be assigned to an ageing factor (2). Furthermore, there are experimental studies where no significant effect of an assumed ageing factor was found (3). And finally there are genes included that are homologous to known ageing-relevant genes for which there is no experimental evidence. They are considered as putative ageing-relevant genes with computational evidence (4).
Order of importance:

  1. yes (Experimental Analysis)
  2. yes, but no ageing factor assigned (Experimental Analysis)
  3. no (Experimental Analysis)
  4. putative (Computational Analysis)
The color indicating the ageing relevance type of an observation may differ from the corresponding color for the ageing factor related to this observation. The reason is that for ageing factors associated with more than one observation, the most important observation color is chosen as ageing factor color. This is always the color with the lowest number in the order given above.

Ageing phenotype observations are considered as experimental analysis. They confirm or reject the ageing relevance for particular ageing factor(s). For genes that are homologous to known ageing-relevant genes there is thus far no experimental evidence. They are considered as candidate genes.
Due to the different data structures of ageing phenotype observation data integrated from other databases we subdivide these observations into type 1 and 2. Observations of type 1 contain the phenotype data mostly unseparated within a single description. Observations of type 2 contain lifespan data in a more structured form (e.g.: separated into lifespan effect, lifespan change, lifespan value). Currently there might be an overlap between the observations of type 1 and 2 from the same source, namely GenAge. But we are working on a reduction of this overlap.

Ageing Relevance:
1 ... 100 [next icon]
# Observation Stable ID Species Gene Symbol NCBI Gene ID Other Ageing Factor Name Description PubMed Source
1 OB_005086 Homo sapiens A2M 2 A2M inhibits proteinases. Knockout mice are more resistant to endotoxins [[PubMed icon] 7544347], though they have not been shown to live longer. In humans, A2M has been associated with neurodegenerative diseases [[PubMed icon] 9697696], but a direct association with human ageing has not been established. 7544347, 9697696 [GenAge icon]GenAge
2 OB_005087 Homo sapiens APOE 348 APOE is involved in lipid metabolism. Mice without APOE show dysregulations in lipid metabolism, having higher plasma cholesterol levels and developing arterial lesions [[PubMed icon] 1411543], and presenting severe atherosclerosis and cutaneous xanthomatosis [[PubMed icon] 11726538]. They also have a significantly shorter lifespan than wild-type [[PubMed icon] 11726538]. Neurodegeneration has also been reported in APOE-null mice [[PubMed icon] 7498401]. Several polymorphisms in the human APOE gene have been associated with diseases, such as increased risk of myocardial infarction [[PubMed icon] 10587578], and polymorphisms in APOE have been linked to human longevity [[PubMed icon] 8136829]. Clearly, APOE has animpact on age-related diseases, such as atherosclerosis and neurodegeneration, but its overall impact on the human ageing process remains to be determined. 1411543, 7498401, 8136829, 10587578, 11726538 [GenAge icon]GenAge
3 OB_005088 Homo sapiens GSS 2937 GSS is involved in redox regulation and oxidative defence. Mutations in the human GSS gene cause 5-oxoprolinuria [[PubMed icon] 8896573]. There is no evidence directly linking GSS to ageing in humans or in model organisms. 8896573 [GenAge icon]GenAge
4 OB_005089 Homo sapiens GSTA4 2941 GSTA4 is part of the glutathione system involved in oxidative protection [[PubMed icon] 12956415]. Expression of GSTA4 increases in the aged rat cerebral cortex [[PubMed icon] 12600725]. There is no causal evidence, however, linking GSTA4 to ageing in humans or in model organisms. 12600725, 12956415 [GenAge icon]GenAge
5 OB_005090 Homo sapiens GSTP1 2950 GSTP1 is part of the glutathione system involved in oxidative protection [[PubMed icon] 12956415]. Overexpression of a homologue of GSTP1 in roundworms extended lifespan by about 22% [[PubMed icon] 16164425]. There is some evidence linking polymorphisms in the human GSTP1 gene to Parkinson's disease induced by pesticides [[PubMed icon] 9802272], but GSTP1's role in human ageing remains unknown. 9802272, 12956415, 16164425 [GenAge icon]GenAge
6 OB_005091 Homo sapiens GTF2H2 2966 GTF2H2 is a component of the core TFIIH basal transcription factor that is involved in DNA repair and transcription [[PubMed icon] 14550632]. The association of TFIIH with some ageing-related genes, such as ERCC2 [[PubMed icon] 10416615], suggests GTF2H2 may also play a role in ageing, though further studies are needed to investigate this hypothesis. 10416615, 14550632 [GenAge icon]GenAge
7 OB_005092 Homo sapiens H2AFX 3014 Histones such as H2AFX are part of the nucleosome, which consists of DNA wrapped around histones. H2AFX has been involved in DNA repair together with, among others, NBN and TP53 [[PubMed icon] 11934988]. H2AFX-null mice were growth retarded and showed signs of genomic instability [[PubMed icon] 11934988]. Whether H2AFX plays a role in human ageing remains to be determined. 11934988 [GenAge icon]GenAge
8 OB_005093 Homo sapiens HBP1 26959 HBP1 has been related to DNA unwinding and stress response [[PubMed icon] 9030690]. In mice, HBP1 and other HMG chromosomal proteins have been shown to suffer alterations at various levels during ageing [[PubMed icon] 2162167], but HBP1 has not been directly related to human ageing. 2162167, 9030690 [GenAge icon]GenAge
9 OB_005094 Homo sapiens HDAC1 3065 HDAC1 performs the deacetylation of histones and is an important player in may processes such as development, transcriptional regulation, and cell cycle progression [[PubMed icon] 12429021]. Homologues of HDAC1 have been linked to longevity in yeast [[PubMed icon] 10512855] and to ageing and caloric restriction in fruit flies [[PubMed icon] 12459580]. Whether HDAC1 is involved in human ageing, however, is unknown. 10512855, 12429021, 12459580 [GenAge icon]GenAge
10 OB_005095 Homo sapiens HDAC2 3066 HDAC2 performs the deacetylation of histones and is an important player in may processes such as development, transcriptional regulation, and cell cycle progression [[PubMed icon] 12429021]. Homologues of HDAC2 have been linked to longevity in yeast [[PubMed icon] 10512855] and to ageing and caloric restriction in fruit flies [[PubMed icon] 12459580]. Whether HDAC2 is involved in human ageing, however, is not known. 10512855, 12429021, 12459580 [GenAge icon]GenAge
11 OB_005096 Homo sapiens HDAC3 8841 HDAC3 performs the deacetylation of histones and likely participates in transcriptional regulation [[PubMed icon] 12429021]. Homologues of HDAC3 have been linked to longevity in yeast [[PubMed icon] 10512855] and to ageing and caloric restriction in fruit flies [[PubMed icon] 12459580]. Its relation to human ageing is not known, yet because of its many functions, it is possible that HDAC3 plays some role on ageing. 10512855, 12429021, 12459580 [GenAge icon]GenAge
12 OB_005097 Homo sapiens HELLS 3070 HELLS is a transcriptional regulator acting on chromatin and maybe affecting cellular proliferation. It has been linked to leukaemia [[PubMed icon] 9878251]. About 60% of HELLS-null mice die shortly after birth. Survivors do not commonly live more than a month but exhibit growth retardation and signs of premature ageing [[PubMed icon] 15105378]. Whether HELLS impacts on human ageing is unknown. 9878251, 15105378 [GenAge icon]GenAge
13 OB_005098 Homo sapiens APP 351 APP has different functions. It is a cell surface receptor, interacts with many other proteins, and may regulate neurite growth. Clearly, APP is an important player in Alzheimer's disease [[PubMed icon] 1925564], though it is not known whether it is related to other aspects of ageing. 1925564 [GenAge icon]GenAge
14 OB_005099 Homo sapiens HESX1 8820 HESX1 is an important regulator of development and, particularly, of pituitary development. It may antagonize the transcriptional activities of PROP1 [[PubMed icon] 11283314]. Mice without HESX1 develop pituitary dysplasia. Mutations in the human HESX1 gene have been associated with septooptic dysplasia [[PubMed icon] 9620767]. As a member of the hypothalamus-pituitary system, HESX1 might, in theory, be involved in ageing even if it has so far not been directly associated with human ageing. 9620767, 11283314 [GenAge icon]GenAge
15 OB_005100 Homo sapiens HIC1 3090 HIC1 is a transcriptional repressor. It suppresses age-dependent development of cancer in mice together with TP53. HIC1 also forms a complex with SIRT1 that represses SIRT1 expression. Ageing increases promoter hypermethylation and epigenetic silencing of HIC1 [[PubMed icon] 16269335]. Therefore, HIC1 might play some role in ageing, though further studies are warranted. 16269335 [GenAge icon]GenAge
16 OB_005101 Homo sapiens HIF1A 3091 HIF1A is a transcription factor that responds to oxidative stress and oxygen [[PubMed icon] 12628185]. Changes in HIF1A with age have been reported in rats and could be related to age-related pathologies [[PubMed icon] 16439820], such as neurodegeneration [[PubMed icon] 16026332]. Deficiencies in HIF1A have not been associated with ageing in mice [[PubMed icon] 11792862]. Further evidence is needed to directly link HIF1A to human ageing. 11792862, 12628185, 16026332, 16439820 [GenAge icon]GenAge
17 OB_005102 Homo sapiens HMGB1 3146 HMGB1 has been related to DNA unwinding, stress response, and maintenance of genome stability [[PubMed icon] 12110890]. HMGB1-null mice die shortly after birth [[PubMed icon] 10391216]. In mice, HMGB1 and other HMG chromosomal proteins have been shown to suffer alterations at various levels during ageing [[PubMed icon] 2325444], though HMGB1 has not been directly related to human ageing. 2325444, 10391216, 12110890 [GenAge icon]GenAge
18 OB_005103 Homo sapiens HMGB2 3148 HMGB2 has been related to DNA unwinding and stress response. In mice, HMGB2 and other HMG chromosomal proteins have been shown to suffer alterations at various levels during ageing [[PubMed icon] 2325444], though HMGB2 has not been directly related to human ageing. 2325444 [GenAge icon]GenAge
19 OB_005104 Homo sapiens HOXB7 3217 HOXB7 is a member of the homeobox family, also called HOX, crucial in morphogenesis and development [[PubMed icon] 2574852]. The expression of many HOX genes, including HOXB7, declines with age, even prior to adulthood [[PubMed icon] 9457903]. An association of HOX genes with longevity has been proposed [[PubMed icon] 12297269], though there is no direct evidence linking HOXB7 to human ageing. 2574852, 9457903, 12297269 [GenAge icon]GenAge
20 OB_005105 Homo sapiens HOXC4 3221 HOXC4 is a member of the homeobox family, also called HOX, crucial in morphogenesis and development [[PubMed icon] 2574852]. The expression of many HOX genes, including HOXC4, declines with age, even prior to adulthood [[PubMed icon] 9457903]. HOXC4 also interacts with XRCC6 and PRKDC [[PubMed icon] 11279128]. An association of HOX genes with longevity has been proposed [[PubMed icon] 12297269], though there is no direct evidence linking HOXC4 to human ageing. 2574852, 9457903, 11279128, 12297269 [GenAge icon]GenAge
21 OB_005106 Homo sapiens HRAS 3265 HRAS is a member of the RAS family of oncogenes and probably plays a role in cell growth and differentiation. In roundworms, the RAS pathway has been shown to influence development and ageing in conjunction with INS/IGF1 [[PubMed icon] 16164423], and RAS signalling has been associated with brain degeneration in fruit flies [[PubMed icon] 12529440]. Although HRAS is involved in cancer and cellular senescence [[PubMed icon] 11971980], its role in human ageing is unknown. 11971980, 12529440, 16164423 [GenAge icon]GenAge
22 OB_005107 Homo sapiens HSF1 3297 A transcription factor that is activated upon heat shock, HSF1 regulates heat-shock response genes and has been associated with ageing in lower life forms. In roundworms, reducing the activity of a HSF1 homologue appears to accelerate ageing while overexpressing it extends lifespan [[PubMed icon] 12750521]. In mammals, stress-response appears to diminish with age and it has been reported that HSF1 in aged rats exhibits a decreased ability to bind DNA [[PubMed icon] 12470898]. Disruption of HSF1 in mice results in multiple defects, including increased prenatal lethality, growth retardation, female infertility, and increased susceptibility to stress [[PubMed icon] 10545106]. Although HSF1 has not been directly linked to human ageing, it is possible HSF1 plays some role in human ageing. 10545106, 12470898, 12750521 [GenAge icon]GenAge
23 OB_005108 Homo sapiens HSP90AA1 3320 Also known as Hsp90, HSP90AA1 is a molecular chaperone. Similar proteins have been suggested to impact on the ageing process of model organisms [[PubMed icon] 11518492]. HSP90AA1 is affected by ageing in rats [[PubMed icon] 12470839], though no evidence has directly linked HSP90AA1 to human ageing. 11518492, 12470839 [GenAge icon]GenAge
24 OB_005109 Homo sapiens APTX 54840 APTX is a member of the histidine triad superfamily encoding a number of transcripts. The APTX protein appears to be involved in DNA repair, and it interacts with DNA repair pathways as well as with ageing-related genes [[PubMed icon] 14755728]. Mutations in APTX have been associated with ataxia-ocular apraxia, a neurological disorder, as well as increased susceptibility to genotoxic stress [[PubMed icon] 15044383]. APTX has not been directly linked to human ageing, though a potential role should not be discarded. 14755728, 15044383 [GenAge icon]GenAge
25 OB_005110 Homo sapiens HSPA1A 3303 The HSPA1A protein, also known as hsp72 or hsp70, is a stress-induced chaperone [[PubMed icon] 12677068]. Results from invertebrates have suggested that heat-shock proteins, such as HSPA1A, are involved in ageing. Overexpression of hsp70, a homologue of HSPA1A, extends lifespan in fruit flies [[PubMed icon] 9363888]. Induction of HSPA1A after ischemia is diminished in aged rat hearts [[PubMed icon] 7977810]. Overexpression of HSPA1A in mice with spinocerebellar ataxia type 1 offered protection against this disease, suggesting HSPA1A could protect against neurodegeneration [[PubMed icon] 11448943]. However, in a more recent study, overexpression of hsp70 in mice was associated with growth retardation, tumor formation, and early death [[PubMed icon] 19072255]. Whether HSPA1A is related to human ageing remains to be determined. 7977810, 9363888, 11448943, 12677068, 19072255 [GenAge icon]GenAge
26 OB_005111 Homo sapiens HSPA1B 3304 HSPA1B is involved in stress response and recognition of abnormal proteins, but also in signalling cascades. Results from invertebrates have suggested that heat-shock proteins, such as hsp70, a homologue of HSPA1B, are involved in ageing [[PubMed icon] 9363888]. Whether HSPA1B is involved in human ageing is unknown. 9363888 [GenAge icon]GenAge
27 OB_005112 Homo sapiens HSPA8 3312 Also called hsc70 and hsp73, HSPA8 is a constitutively expressed chaperone. Age-related changes in stress response have been reported in rats, though HSPA8 levels do not appear to change with age [[PubMed icon] 8473688]. Whether HSPA8 plays any role in human ageing remains to be determined. 8473688 [GenAge icon]GenAge
28 OB_005113 Homo sapiens HSPA9 3313 HSPA9 appears to be involved in apoptosis and maybe cellular proliferation. It could also be a molecular chaperone. Roundworms with extra copies of Hsp70F, a HSPA9 homologue, live about 40% longer than controls [[PubMed icon] 11959102]. A role for HSPA9 in human ageing has not been established. 11959102 [GenAge icon]GenAge
29 OB_005114 Homo sapiens HSPD1 3329 HSPD1 plays a role in stress response in the mitochondria [[PubMed icon] 2645524]. Heat-shock proteins have been suggested as a player in the ageing of model organisms such as invertebrates. Age-related changes in heat-shock proteins, including HSPD1, have also been reported in rats [[PubMed icon] 16518701]. A mutation in the human HSPD1 gene has been associated with spastic paraplegia [[PubMed icon] 11898127]. HSPD1's relevance to human ageing remains to be determined. 2645524, 11898127, 16518701 [GenAge icon]GenAge
30 OB_005115 Homo sapiens HTT 3064 Mostly famous for causing Huntington disease, the exact functions of HTT are still unknown. While HTT appears to be involved in age-related changes [[PubMed icon] 11408619], its exact role in human ageing is still being studied. In mice however, the deletion of the polyglutamine stretch resulted in the extension of mean and maximal lifespan [[PubMed icon] 20140187]. 11408619, 20140187 [GenAge icon]GenAge
31 OB_005116 Homo sapiens IGF1 3479 IGF1 is a hormone that stimulates growth and mediates many of the actions of GH1. Like GH1, its circulating levels decline with age in humans. The GH1/IGFI axis is considered a possible player in the ageing process of several model organisms, including rodents [[PubMed icon] 12393957]. IGF1 null mice show growth deficiency and usually are not viable, though some can reach adulthood [[PubMed icon] 8402901]. Mutations that lower IGF1 levels in mice retard growth and extend lifespan [[PubMed icon] 12057928], even if a definitive causative relation between IGF1 and ageing has not been demonstrated. Genotype combinations in the human PIK3CB and IGF1R genes have been related to plasma IGF1 levels and longevity [[PubMed icon] 12843179]. Cardiac specific overexpression of IGF1 results in a 23% increase in median lifespan, though no increase in maximum lifespan [[PubMed icon] 17973971]. In humans, IGF1 levels have been associated with several pathologies. High levels of IGF1 have been found to be associated with risk of breast cancer [[PubMed icon] 9593409]. On the other hand, low levels of IGF1 have been associated with osteoporosis [[PubMed icon] 10752709]. Despite being a putative regulator of ageing, IGF1's exact influence on human ageing is not known. 8402901, 9593409, 10752709, 12057928, 12393957, 12843179, 17973971 [GenAge icon]GenAge
32 OB_005117 Homo sapiens IGF1R 3480 The receptor for IGF1, IGF1R mediates the activation of the IGF1-stimulated signalling cascade. Evidence from model organisms, including results from flies [[PubMed icon] 11292875] and roundworms [[PubMed icon] 8247153], relates IGF1R homologues to ageing, most likely as part of the GH1/IGF1 axis. Mice heterozygous for IGF1R live 26% longer, though it is unclear whether they age slower. Null mutants are not viable [[PubMed icon] 12483226]. The IGF1/GH1 axis appears to impact on ageing in model organisms, including rodents, and so IGF1R may affect human ageing. In humans, IGF1R has been implicated with growth retardation [[PubMed icon] 1849352], and genotype combinations in the human IGF1R and PIK3CB genes have been related to plasma IGF1 levels and longevity [[PubMed icon] 12843179]. 1849352, 8247153, 11292875, 12483226, 12843179 [GenAge icon]GenAge
33 OB_005118 Homo sapiens IGF2 3481 Like IGF1, IGF2 is involved in growth and development. Unlike IGF1, IGF2 appears to be only active at early stages of development, such as embryonic growth. IGF2's role in ageing is unproven and its interest derives mostly from its connection with IGF1 and how the IGF1/GH1 axis appears to regulate ageing in model organisms [[PubMed icon] 10077613]. Mice with disrupted IGF2 are growth-deficient but their lifespan has not been studied [[PubMed icon] 2330056]. Polymorphisms in the human IGF2 gene have been associated with body mass index in adult males [[PubMed icon] 11448941]. 2330056, 10077613, 11448941 [GenAge icon]GenAge
34 OB_005119 Homo sapiens IGFBP2 3485 IGF Binding Protein 2 is encoded by the leptin(LEP)-regulated IGFBP2 gene and binds IGF proteins, especially IGF2. IGFBP2 inhibits IGF-mediated growth and developmental rates. In mice, overexpression of IGFBP2 reversed diabetes in insulin-resistant and diet-induced obese mice, as well as insulin-deficient streptozotocin-treated mice [[PubMed icon] 20074524]. Although it is tempting to suggest a role for IGFBP2 in age-related diseases and perhaps in ageing, due to its links to IGFs and LEP, so far, no direct evidence linking IGFBP2 to human ageing is available. 20074524 [GenAge icon]GenAge
35 OB_005120 Homo sapiens AR 367 AR is involved in transcriptional regulation and cellular proliferation and differentiation [[PubMed icon] 12370412]. Disruption of AR in mice results in insulin (INS) and leptin (LEP) resistance, which suggests that AR may contribute to certain age-related diseases such as type 2 diabetes and cardiovascular disease [[PubMed icon] 15919793]. Its exact role in human ageing is unknown. 12370412, 15919793 [GenAge icon]GenAge
36 OB_005121 Homo sapiens IGFBP3 3486 IGFBP3 is a member of the IGFBP family that regulates IGF1 and IGF2 by altering the interaction of IGFs with their cell surface receptors. Some evidence suggests that IGFBP3 influences age-related changes in lean body mass [[PubMed icon] 12865482], but so far it has not been directly linked to human ageing. 12865482 [GenAge icon]GenAge
37 OB_005122 Homo sapiens IL2 3558 IL2 is a cytokine that has been associated with age-related changes at the immune system level [[PubMed icon] 10840474]. Studies of polymorphisms in the human IL2 gene, however, have so far failed to find an association with human longevity [[PubMed icon] 12633940]. 10840474, 12633940 [GenAge icon]GenAge
38 OB_005123 Homo sapiens IL2RG 3561 A crucial component in IL2 signal transduction, IL2RG could be related to the age-associated functional decline in the immune system [[PubMed icon] 10840474]. 10840474 [GenAge icon]GenAge
39 OB_005124 Homo sapiens IL6 3569 IL6 is involved in a variety of processes such as development, differentiation, and inflammation [[PubMed icon] 8426042]. Mice without IL6 have a defective hepatocyte regeneration and develop liver failure [[PubMed icon] 8910279]. Transgenic mice expressing high levels of IL6 have a reduced growth rate and low levels of IGF1 [[PubMed icon] 9045866]. Its levels appear to increase with age, possibly associating IL6 with age-related changes, such as chronic inflammatory diseases [[PubMed icon] 10774463]. Polymorphisms in the human IL6 gene have been linked to age-related diseases, such as cardiovascular diseases [[PubMed icon] 15036420], though they have not been associated with longevity [[PubMed icon] 11640949]. A role for IL6 in human ageing is plausible though largely obscure. 8426042, 8910279, 9045866, 10774463, 11640949, 15036420 [GenAge icon]GenAge
40 OB_005125 Homo sapiens IL7 3574 IL7 stimulates the proliferation of lymphoid progenitors. Mice without IL7 cease producing B lymphocyte after 7 weeks of age [[PubMed icon] 11602642]. Declines with age in IL7 production have been associated with thymic atrophy [[PubMed icon] 11772533]. Although IL7 could play a role age-related changes, such as ageing of the immune system, its role in human ageing is unknown. 11602642, 11772533 [GenAge icon]GenAge
41 OB_005126 Homo sapiens IL7R 3575 IL7R is involved in inflammation and immune response. Though a role in human ageing has not been demonstrated, it is possible that IL7R is related to age-related changes and pathologies, namely, at the level of the immune system [[PubMed icon] 8692964]. 8692964 [GenAge icon]GenAge
42 OB_005127 Homo sapiens INS 3630 Insulin is produced by cells in the islets of Langerhans in the pancreas. It decreases blood glucose concentration and regulates the cellular metabolism of monosaccharides, amino acids and fatty acids. As with IGF1, INS may be involved in the ageing process of model organisms [[PubMed icon] 12610294]. In roundworms, expression of the human insulin gene enhances dauer formation and slightly increases lifespan [[PubMed icon] 11274053]. Despite the well-established age-related onset of type 2 diabetes, and possible roles of INS in other age-related diseases [[PubMed icon] 12900169], the impact of INS on human ageing is unclear. 11274053, 12610294, 12900169 [GenAge icon]GenAge
43 OB_005128 Homo sapiens INSR 3643 INSR binds insulin (INS) and regulates energy metabolism [[PubMed icon] 10025399]. Evidence from model organisms, including results from fruit flies [[PubMed icon] 11292875] and roundworms [[PubMed icon] 9252323], relates INSR homologues to ageing, most likely as part of the GH1/IGF1 axis. In mice, disruption of INSR in adipose tissue extends longevity but does not appear to delay ageing [[PubMed icon] 12543978]. Mutations in the human INSR gene have been associated with insulin resistance [[PubMed icon] 2544998]. INSR could play a role in some human age-related pathologies, but it is not known whether it is a major player in human ageing. 2544998, 9252323, 10025399, 11292875, 12543978 [GenAge icon]GenAge
44 OB_005129 Homo sapiens IRS1 3667 IRS1 and IRS2 mediate many of the cellular actions of insulin (INS). Results from model organisms suggest IRS1 is involved in the IGF1/GH1 axis that could regulate ageing. In Drosophila, loss of chico, an insulin receptor substrate, extends lifespan [[PubMed icon] 11292874]. Median lifespan was extended 18% in knockout mice from both sexes and 32% in females. Female animals displayed signs of resistance to ageing markers in skin, bone, immune system, and motor dysfunction, in spite of mild, lifelong insulin resistance. Heterozygous animals had normal lifespans [[PubMed icon] 17928362]. IRS1 may also be involved in the extended lifespan of some mouse strains [[PubMed icon] 11927387]. In humans, mutations in IRS1 have been associated with diabetes [[PubMed icon] 12679424] and atherosclerosis [[PubMed icon] 10591678]. While it appears that IRS1 plays a role in some human age-related pathologies, its exact impact on the human ageing process is unknown. 10591678, 11292874, 11927387, 12679424, 17928362 [GenAge icon]GenAge
45 OB_005130 Homo sapiens IRS2 8660 IRS2 and IRS1 mediate many of the cellular actions of insulin (INS). Results from model organisms suggest IRS2 is involved in the IGF1/GH1 axis that appears to influence ageing in model organisms. In Drosophila, loss of chico, an insulin receptor substrate, extends lifespan [[PubMed icon] 11292874]. IRS2 brain-specific knockout mice were overweight, hyperinsulinemic, glucose intolerant, yet more active and lived up to 18% longer [[PubMed icon] 17641201]. In another experiment, however, IRS2 knockout mice were reported to have a shorter median lifespan. Heterozygous animals had normal lifespans [[PubMed icon] 17928362]. IRS2 may also be involved in the extended lifespan of other mouse strains [[PubMed icon] 11927387]. In humans, mutations in IRS2 have been associated with diabetes [[PubMed icon] 11473060]. IRS2 likely plays a role in some human age-related pathologies, but its exact impact on the human ageing process is unknown. 11292874, 11473060, 11927387, 17641201, 17928362 [GenAge icon]GenAge
46 OB_005131 Homo sapiens ARHGAP1 392 ARHGAP1 a GTPase activator of several proteins. In effect, it acts as a negative regulator of CDC42. Gene targeting of ARHGAP1 in mice results in a short lifespan of about 12 months and the development of multiple premature ageing-like phenotypes, suggesting that this gene may play a role in mammalian ageing [[PubMed icon] 17227869]. 17227869 [GenAge icon]GenAge
47 OB_005132 Homo sapiens JAK2 3717 JAK2 is a tyrosine kinase involved in cytokine receptor signalling. Disruption of JAK2 causes embryonic lethality due to the absence of definitive erythropoiesis [[PubMed icon] 9590173]. Its signalling functions and its association with a number of genes previously linked to ageing suggest JAK2 may play some role in ageing, even though a direct association of JAK2 with human ageing has not been established. 9590173 [GenAge icon]GenAge
48 OB_005133 Homo sapiens JUN 3725 JUN is an important transcription factor that is also a member of the AP-1 transcriptional complex. Its signalling pathway has been related to ageing in fruit flies [[PubMed icon] 14602080] and roundworms [[PubMed icon] 15767565], though a direct role of JUN has not been demonstrated. Results from mice have shown that AP-1's DNA-binding activity decreases with age [[PubMed icon] 8806666]. JUN-null mice die at embryonic stages [[PubMed icon] 8371760]. Further research is needed to assess JUN'1 role in human ageing. 8371760, 8806666, 14602080, 15767565 [GenAge icon]GenAge
49 OB_005134 Homo sapiens JUND 3727 A possible oncogene and transcriptional activator, JUND is part of the AP-1 redox-regulated transcription complex that may play a role in some age-related changes [[PubMed icon] 10978675]. The exact relation of AP-1 to human ageing is unclear, however. Mice lacking junD exhibited persistent hypoglycemia due to enhanced insulin secretion and features of premature aging (cataracts, slight hair loss, graying, varying degrees of cachexia, and lordokyphosis), and had a shortened lifespan [[PubMed icon] 18249171]. An impaired activation of AP-1 and altered expression of constituent proteins in adrenal nuclear extracts from rats was also observed during ageing [[PubMed icon] 11389931]. A similar change was seen during the ageing of human fibroblasts [[PubMed icon] 11557282]. 10978675, 11389931, 11557282, 18249171 [GenAge icon]GenAge
50 OB_005135 Homo sapiens KCNA3 3738 The potassium voltage-gated channel, shaker-related subfamily, member 3, also known as KCNA3 or Kv1.3, is involved in the repolarization of nerve cells following an action potential. It also plays an essential role in T-cell proliferation and activation. In the murine model, null mice weigh less than their WT counterparts, have modified ingestive behaviors, are resistant to fat deposition following a moderately high-fat dietary regime and have improved longevity and fecundity. Moreover, gene-targeted deletion in the short-lived MC4R-null mice returned the lifespan of these mice to approximately wild type levels [[PubMed icon] 18542083]. A variant in the promoter of the Kv1.3 gene was found associated, in a genome-wide study among nondiabetic, with impaired glucose tolerance and lower insulin sensitivity [[PubMed icon] 16317062]. KCNA3 is also involved in age-related diseases, like Alzheimer's Disease and cancer. For example, an aberrant glutamate-dependent modulation of Kv1.3 channels was found in T lymphocytes of AD patients [[PubMed icon] 19850126] and it was shown that the inhibition of Kv1.3 has an anti-proliferative effect, blocking proliferation of human lung adenocarcinoma cells [[PubMed icon] 21087602]. In breast adenocarcinoma, Kv1.3 gene expression is decreased probably due to DNA methylation, and is associated with poorly differentiated tumors and younger patients [[PubMed icon] 19590190]. A reduced expression of Kv1.3 was also found in human prostate cancer [[PubMed icon] 17546508]. So far there has been no direct evidence linking KCNA3 to human longevity and further research is needed. 16317062, 17546508, 18542083, 19590190, 19850126, 21087602 [GenAge icon]GenAge
51 OB_005136 Homo sapiens KL 9365 The KL gene encodes two proteins: one membrane protein and one secreted transcript that acts as a circulating hormone. Mice mutant for KL show multiple signs of accelerated ageing [[PubMed icon] 9363890]. In contrast, overexpression of KL in mice increases lifespan by 20-30%, perhaps through a repression of intracellular INS/IGF1 signals [[PubMed icon] 16123266]. KL alleles have also been implicated in human longevity and age-related diseases [[PubMed icon] 11792841]. Even though its exact functions remain a mystery, KL may be involved in calcium metabolism and in a vitamin D endocrine system. Premature ageing phenotypes in mice mutant for KL are largely rescued by keeping the animals on a vitamin-D-deficient diet [[PubMed icon] 14528024]. KL might also exert its actions through FGF23 [[PubMed icon] 16436388]. It is plausible that KL plays some role in human ageing but more work is necessary to confirm this notion and elucidate the mechanisms involved. 9363890, 11792841, 14528024, 16123266, 16436388 [GenAge icon]GenAge
52 OB_005137 Homo sapiens LEP 3952 LEP is secreted from adipose tissues and is involved in food intake and energy expenditure. Mice with mutations in the LEP gene are obese [[PubMed icon] 7984236]. Female mice injected with LEP grew slower but had an early onset of reproductive function [[PubMed icon] 8974400]. LEP deficiency in humans is associated with early-onset obesity [[PubMed icon] 9202122]. Due to its impact on energy metabolism and reproduction, LEP could be related to neuroendocrine systems involved in ageing as well as play a part in age-related diseases such as diabetes and atherosclerosis. 7984236, 8974400, 9202122 [GenAge icon]GenAge
53 OB_005138 Homo sapiens LEPR 3953 LEPR is the receptor for leptin (LEP) and is involved in LEP's signal transduction [[PubMed icon] 8608603]. The obese spontaneously hypertensive Koletsky rat has been associated with mutations in LEPR [[PubMed icon] 8841178]. Deletion of LEPR in neurons of mice results in obesity [[PubMed icon] 11602618]. Polymorphisms in the human LEPR gene have been associated with obesity, body mass index, and fat mass [[PubMed icon] 11354636]. Like LEP, LEPR plays a role in fat metabolism and so could be involved in some aspects of age-related deterioration. 8608603, 8841178, 11354636, 11602618 [GenAge icon]GenAge
54 OB_005139 Homo sapiens LMNA 4000 Hutchinson-Gilford's progeroid syndrome, caused by a mutation in LMNA, is characterized by features resembling accelerated ageing [[PubMed icon] 12714972]. LMNA encodes both lamin A and C, two components of the lamina, a layer of the inner nuclear membrane that may interact with chromatin [[PubMed icon] 10651242]. Its exact functions remain unknown. Other pathologies not resembling accelerated ageing have also been associated with mutations in LMNA, like Emery-Dreifuss muscular dystrophy [[PubMed icon] 10080180]. Although further research is needed to understand LMNA, it is one promising candidate for a gene related to human ageing. 10080180, 10651242, 12714972 [GenAge icon]GenAge
55 OB_005140 Homo sapiens LMNB1 4001 LMNAB1 is, like LMNA, part of the nuclear lamina [[PubMed icon] 8838815]. LMNB1-null mice die shortly after birth [[PubMed icon] 15232008]. If the nuclear lamina is a player in human ageing, as some results from LMNA suggest [[PubMed icon] 15688064], then it is possible that LMNB1 also plays some role in human ageing. 8838815, 15232008, 15688064 [GenAge icon]GenAge
56 OB_005141 Homo sapiens LRP2 4036 LRP2 binds CLU and other ligands and may play a role in cholesterol homeostasis. It may also help regulate the release of parathyroid hormone [[PubMed icon] 8706697]. Disruption of LRP2 in mice results in defective forebrain development [[PubMed icon] 8710893]. Its role, if any, in human ageing is unclear. 8706697, 8710893 [GenAge icon]GenAge
57 OB_005142 Homo sapiens ARNTL 406 ARNTL forms a heterodimer with CLOCK, which activates circadian rhythm-associated genes. Mice deficient in ARNTL have an impaired circadian behavior, reduced lifespan, and display symptoms of premature ageing associated in some tissues with increased levels of reactive oxygen species [[PubMed icon] 16847346]. As such, ARNTL might play some role in mammalian ageing. 16847346 [GenAge icon]GenAge
58 OB_005143 Homo sapiens MAP3K5 4217 MAP3K5, also called ASK1, is involved in stress response and apoptosis [[PubMed icon] 8974401]. Disruption of MAP3K5 in mice attenuates left ventricular remodelling [[PubMed icon] 14665690]. It is possible that MAP3K5 is related to age-related changes in stress response witnessed in a number of animal models. MAP3K5 has not been directly linked to human ageing. 8974401, 14665690 [GenAge icon]GenAge
59 OB_005144 Homo sapiens MAPK14 1432 Also known as p38, MAPK14 is activated in response to cellular stress and it can phosphorylate a number of transcription factors. It is also involved in the production of IL6 [[PubMed icon] 12419465], and is an important player in cellular senescence [[PubMed icon] 12581156]. Mice without MAPK14 are anaemic due to failed definitive erythropoiesis [[PubMed icon] 10943842]. Transgenic mice with induced MAPK14 activity in the heart died in 7-9 weeks [[PubMed icon] 11593045]. MAPK14's responsiveness may change with ageing in mouse cells [[PubMed icon] 12885591]. A role for MAPK14 in human ageing is so far unknown. 10943842, 11593045, 12419465, 12581156, 12885591 [GenAge icon]GenAge
60 OB_005145 Homo sapiens MAPK3 5595 Also called ERK1, MAPK3 is involved in stress response signalling and maybe in cell cycle control. MAPK3-null mice are viable and fertile but have defective thymocyte maturation [[PubMed icon] 10558995]. Changes in stress response have been reported during murine ageing that could be a result of changes in MAPK3 [[PubMed icon] 10795716]. The relevance of MAPK3 to human ageing remains undetermined. 10558995, 10795716 [GenAge icon]GenAge
61 OB_005146 Homo sapiens MAPK8 5599 MAPK8, also known as JNK1, encodes many transcripts and is an important player in stress response. In invertebrates, there is evidence linking JNK signalling to ageing. Fruit flies with mutations that augment JNK signalling live longer [[PubMed icon] 14602080]. Overexpression of JNK in roundworms also increases lifespan [[PubMed icon] 15767565]. Changes in JNK1 with age have been reported in rat hepatocytes [[PubMed icon] 8631968]. MAPK8-null mice showed defective T cell differentiation [[PubMed icon] 9851932]. Mice without MAPK8 and MAPK9 die at embryonic stages [[PubMed icon] 10559486]. In mouse models of obesity, absence of MAPK8 decreased adiposity and improved insulin (INS) sensitivity [[PubMed icon] 12447443]. Although MAPK8 could play a role in ageing-related diseases, further research is needed to determine how MAPK8 is related to human ageing. 8631968, 9851932, 10559486, 12447443, 14602080, 15767565 [GenAge icon]GenAge
62 OB_005147 Homo sapiens MAPK9 5601 Also called JNK2, MAPK9 encodes many transcripts and is an important player in stress response. In invertebrates, there is evidence linking JNK signalling to ageing. Fruit flies with mutations that augment JNK signalling live longer [[PubMed icon] 14602080]. Overexpression of JNK in roundworms also increases lifespan [[PubMed icon] 15767565]. Mice without MAPK8 and MAPK9 die at embryonic stages. MAPK9-null mice develop normally [[PubMed icon] 10230788], but are defective in peripheral T-cell activation [[PubMed icon] 10021384]. Further research is needed to determine whether MAPK9 is related to human ageing. 10021384, 10230788, 14602080, 15767565 [GenAge icon]GenAge
63 OB_005148 Homo sapiens MAPT 4137 The MAPT protein appears to promote microtubule assembly and stability. MAPT undergoes complex alternative splicing and its transcripts are differentially expressed in the nervous system depending on neuron type and maturation. Abundant evidence exists linking mutations in MAPT to neurodegenerative diseases in humans [[PubMed icon] 10767321]. 10767321 [GenAge icon]GenAge
64 OB_005149 Homo sapiens MAX 4149 A transcriptional regulator, MAX can act as pro- or anti-apoptotic. Although MAX has not been associated with ageing, it may be a part of its signalling cascade in conjunction with other proteins such as MXI1 [[PubMed icon] 9624006]. 9624006 [GenAge icon]GenAge
65 OB_005150 Homo sapiens MDM2 4193 MDM2 is an oncogene that inhibits TP53 [[PubMed icon] 1535557]. The MDM2 gene encodes multiple transcripts, many of which are tissue-specific. Disruption of MDM2 in mice resulted in increased TP53-dependent apoptosis and defects in multiple haematopoietic lineages [[PubMed icon] 12509446]. Mutations in the human MDM2 gene have been associated with cancer [[PubMed icon] 15550242]. A role for MDM2 in human ageing is unknown. 1535557, 12509446, 15550242 [GenAge icon]GenAge
66 OB_005151 Homo sapiens MED1 5469 MED1 is a transcriptional coactivator involved in embryonic development and important for SP1 activity [[PubMed icon] 10882104]. MED1-null mice die at embryonic stages [[PubMed icon] 10882104]. Certain age-related pathologies, such as heart disease, may be related to PPARs [[PubMed icon] 10839530], but it unclear whether MED1 is a major player in human ageing. 10839530, 10882104 [GenAge icon]GenAge
67 OB_005152 Homo sapiens MLH1 4292 MLH1 is involved in DNA mismatch repair. Mice without MLH1 are infertile and spermatocytes exhibit high levels of prematurely separated chromosomes and cell cycle arrest [[PubMed icon] 8673133]. In humans, MLH1 mutations have been associated with colon cancer [[PubMed icon] 8145827]. Polymorphisms in the human MLH1 gene have been associated with longevity [[PubMed icon] 16474933]. 8145827, 8673133, 16474933 [GenAge icon]GenAge
68 OB_005153 Homo sapiens ATF2 1386 ATF2 is an important transcription factor involved in a variety of functions that may also be involved in oxidative stress response [[PubMed icon] 11069918] and cellular growth arrest and senescence [[PubMed icon] 12419465]. It has not been directly related to human ageing. 11069918, 12419465 [GenAge icon]GenAge
69 OB_005154 Homo sapiens MSRA 4482 MSRA repairs damage resulting from oxidative stress. Results from invertebrates suggest a role for MSRA in ageing. Overexpression of a MSRA homologue in fruit flies extends lifespan [[PubMed icon] 11867705]. Disruption of MSRA in mice decreases longevity and, albeit not proven, might accelerate ageing [[PubMed icon] 11606777]. In humans, MSRA has been associated with age-related diseases, such as Alzheimer's disease [[PubMed icon] 10501213]. Therefore, MSRA could be involved in human ageing. 10501213, 11606777, 11867705 [GenAge icon]GenAge
70 OB_005155 Homo sapiens MT-CO1 4512 Encoded in the mitochondrial DNA, MT-CO1 catalyses the reduction of oxygen to water. COX1, a homologue of MT-CO1, has been related to longevity in the filamentous fungus Podospora anserina [[PubMed icon] 10330149]. Mutations in the human MT-CO1 gene have been associated with several diseases, including neurodegenerative diseases [[PubMed icon] 1634041]. Further research is necessary to understand whether MT-CO1 is involved in human ageing. 1634041, 10330149 [GenAge icon]GenAge
71 OB_005156 Homo sapiens MTOR 2475 The MTOR kinase belongs to the target of rapamycin group of enzymes which regulate cellular growth and proliferation [[PubMed icon] 15780592]. TOR enzymes, homologues of MTOR, have been linked to ageing in lower organisms. In yeast, deletions in the nutrient-responsive TOR pathway increased lifespan, and caloric restriction failed to further increase lifespan [[PubMed icon] 16293764]. Similarly, in roundworms, TOR deficiency more than doubled the lifespan [[PubMed icon] 14668850], and TOR disruption in fruit flies also extended lifespan [[PubMed icon] 15186745]. In invertebrates, a functional link between MTOR and insulin (INS)/IGF1 signalling has been proposed [[PubMed icon] 12559758], which further hints of a role for MTOR in ageing. Further research is needed to determine whether MTOR is associated with human ageing. 12559758, 14668850, 15186745, 15780592, 16293764 [GenAge icon]GenAge
72 OB_005157 Homo sapiens MXD1 4084 MXD1 is involved in apoptosis. It forms with MAX a transcriptional repressor and might antagonize MYC function [[PubMed icon] 12553908]. There is no evidence directly linking MXD1 to human ageing. 12553908 [GenAge icon]GenAge
73 OB_005158 Homo sapiens MXI1 4601 MXI1 is an antagonist of MYC in that it competes with MYC for MAX [[PubMed icon] 8425219]. Mice lacking MXI1 exhibit progressive, multisystem abnormalities and increased susceptibility to tumorigenesis. A role for MXI1 in murine ageing has thus been suggested [[PubMed icon] 9624006]. Mutations in the human MXI1 gene have been linked to cancer [[PubMed icon] 7773287]. Additional, more detailed, studies are necessary to determine whether MXI1 is related to human ageing. 7773287, 8425219, 9624006 [GenAge icon]GenAge
74 OB_005159 Homo sapiens MYC 4609 MYC regulates gene transcription and appears to promote growth. It is also an oncogene [[PubMed icon] 8712067], involved in cellular senescence [[PubMed icon] 16537449]. Among its many interacting partners, MYC has been linked to ageing-related genes such as WRN [[PubMed icon] 12842909] and TERT [[PubMed icon] 9988278], and hence might play some, so far unknown, role in human ageing. 8712067, 9988278, 12842909, 16537449 [GenAge icon]GenAge
75 OB_005160 Homo sapiens NBN 4683 Mutations in NBN cause Nijmegen breakage syndrome, a chromosomal instability syndrome that has been suggested as progeroid [[PubMed icon] 11089984]. NBN is involved in DNA repair, probably of double-strand breaks, in conjunction with other proteins associated with ageing [[PubMed icon] 12422221]. While not proven, NBN could potentially play some role in human ageing. 11089984, 12422221 [GenAge icon]GenAge
76 OB_005161 Homo sapiens NCOR1 9611 NCOR1 is a transcriptional mediator that regulates chromatin condensation. Its exact functions are unknown but there is evidence linking NCOR1 to development [[PubMed icon] 11030619]. Although there is little evidence to suggest NCOR1 influences ageing, due to its relation with several proteins thought to be related to ageing and age-related diseases [[PubMed icon] 12150997], NCOR1 might potentially play some role in human ageing. 11030619, 12150997 [GenAge icon]GenAge
77 OB_005162 Homo sapiens NCOR2 9612 NCOR2, also known as SMRT, is a transcriptional corepressor that maintains the transcriptional silencing of certain target genes. NCOR2 expression and its occupancy on peroxisome proliferator-activated receptor (PPAR) target gene promoters are increased with age in major metabolic tissues. Shifting its repressive activity towards PPARs, by selectively disabling one of its two major receptor-interacting domains, resulted in premature aging and related metabolic diseases accompanied by reduced mitochondrial function and antioxidant gene expression. Additionally, in a preliminary analysis, several human polymorphisms were found to associate with type 2 diabetes and adiponectin levels [[PubMed icon] 21109196]. 21109196 [GenAge icon]GenAge
78 OB_005163 Homo sapiens NFE2L2 4780 NF-E2-related factor 2 (NRF2) is a transcription factor that is activated by oxidative stress and electrophiles and has a role in inducing a number of antioxidative and carcinogen-detoxifying enzymes. Nrf2-deficient mice develop more tumors in response to carcinogens, and caloric restriction is ineffective in suppressing them in the knockout mice. In contrast, caloric restriction remains effective in extending lifespan and increasing insulin sensitivity . In Nrf2-null mice, which were fed a high-fat diet, the levels of hepatic triglycerides and cholesterol in liver were similar to wild type, while the levels of hepatic free fatty acid and malondialdehyde equivalents were higher, suggesting that Nrf2 inhibits lipid accumulation and oxidative stress in the mouse liver . In human fibroblasts, NRF2 shows a declined function in replicative senescence and its silencing leads to premature senescence. NRF2 activation results in the enhanced survival of cells following oxidative stress, whereas continuous treatment leads to lifespan extension of human fibroblasts . NRF2 has been also linked to several human age-related diseases, including atherosclerosis , neurodegenerative diseases , and cancer . The role of NRF2 in human organismal ageing remains still unclear, and further research is needed. [GenAge icon]GenAge
79 OB_005164 Homo sapiens ATM 472 ATM is involved in DNA repair and cell cycle control. It appears to activate DNA repair pathways in response to DNA damage [[PubMed icon] 9363685]. In mice, mutations in ATM in late-generation TERC mutants with short telomeres results in signs of premature ageing starting at about 6 months of age [[PubMed icon] 12540856]. Mutations in human ATM cause ataxia telangiectasia [[PubMed icon] 2005780], an early-onset disease some argue is characterized by signs of premature ageing [[PubMed icon] 9117983]. As such, it is possible ATM plays a role in human ageing. 2005780, 9117983, 9363685, 12540856 [GenAge icon]GenAge
80 OB_005165 Homo sapiens NFKB1 4790 NFKB1 is a component of the NF-kappa-B complex, involved in oxidative pathways and a myriad of other processes. Its role in ageing is unclear, even though NFKB1 appears to be related to age-related changes in inflammation and maybe in other age-related processes too [[PubMed icon] 12380689]. In addition, age-relation changes in NF-kappa-B have been reported for numerous tissues [[PubMed icon] 12020944]. 12020944, 12380689 [GenAge icon]GenAge
81 OB_005166 Homo sapiens NFKB2 4791 NFKB2 is a component of the NF-kappa-B complex, involved in oxidative pathways and a myriad of other processes. Its role in ageing is unclear, even though NFKB2 appears to be related to age-related changes in inflammation and maybe in other age-related processes too [[PubMed icon] 12380689]. In addition, age-relation changes in NF-kappa-B have been reported for numerous tissues [[PubMed icon] 12020944]. 12020944, 12380689 [GenAge icon]GenAge
82 OB_005167 Homo sapiens NFKBIA 4792 NFKBIA inhibits NF-kappa-B by forming a complex with it, and may be involved in inflammation, apoptosis, differentiation, and growth. Downregulation of NFKBIA with age appears to occur in the rat liver [[PubMed icon] 10754263]. Transgenic mice expressing dominant-negative IkB, and exhibiting functional inhibition of NF-kB signaling in endothelial cells, were protected from age-related insulin resistance and vascular senescence and, displayed a prolonged lifespan. In addition, the mice had also decreased oxidative stress markers, increased muscle blood flow, enhanced active-phase locomotor activity, and aortic upregulation of mitochondrial sirtuin-related proteins [[PubMed icon] 22302838]. Whether NFKBIA plays a role in human ageing remains to be determined. 10754263, 22302838 [GenAge icon]GenAge
83 OB_005168 Homo sapiens NGF 4803 A neurotrophin important for the development and maintenance of the central nervous system, NGF stimulates division and differentiation [[PubMed icon] 8463833]. It has been linked with neurodegenerative age-related pathology [[PubMed icon] 10485922]. 8463833, 10485922 [GenAge icon]GenAge
84 OB_005169 Homo sapiens NGFR 4804 A receptor that can bind not only NGF but other neurotrophins, such as BDNF, NGFR mediates neural cell survival and is an important player in development. Results from mice suggest it may be related to brain ageing [[PubMed icon] 1655975], though if and how it impacts on the human ageing process is not known. 1655975 [GenAge icon]GenAge
85 OB_005170 Homo sapiens NOG 9241 NOG appears to be involved in development, though its exact functions remain unclear. Mice without NOG die shortly after birth [[PubMed icon] 9603738]. Overexpression of NOG in mice resulted in severe osteoporosis [[PubMed icon] 12975477]. Mutations in the human NOG gene affect joint morphogenesis [[PubMed icon] 10080184]. NOG may be a factor in bone ageing, but its role in human ageing remains to be established. 9603738, 10080184, 12975477 [GenAge icon]GenAge
86 OB_005171 Homo sapiens NR3C1 2908 NR3C1 is a glucocorticoid receptor that modulates the expression of glucocorticoid-responsive genes. Mice with reduced NR3C1 function show behavioural changes indicative of cognitive impairment [[PubMed icon] 8748120], and in rats neurodegeneration has been associated with NR3C1 [[PubMed icon] 11897693]. A direct role in human ageing has not been demonstrated. 8748120, 11897693 [GenAge icon]GenAge
87 OB_005172 Homo sapiens NRG1 3084 The NRG1 gene encodes multiple transcripts that appear to play a role in neuronal development, differentiation, and apoptosis [[PubMed icon] 8815893]. It may be involved in neurodegenerative pathologies [[PubMed icon] 12145742], but it is unknown whether it plays a role in human ageing. 8815893, 12145742 [GenAge icon]GenAge
88 OB_005173 Homo sapiens PAPPA 5069 PAPPA is a secreted metalloproteinase that cleaves insulin-like growth factor binding proteins. It could be involved in local cell proliferative processes. Genetic deletion of PAPPA in mice extends mean and maximum lifespan by 30-40% and reduces cancer incidence with no reduction in food intake or secondary endocrine abnormalities [[PubMed icon] 17681037]. It has not been established, however, whether the ageing process was delayed in these animals. Knockout mice are also smaller at birth than controls [[PubMed icon] 14973274]. In humans, PAPPA levels have been associated with coronary heart disease [[PubMed icon] 11586954]. 11586954, 14973274, 17681037 [GenAge icon]GenAge
89 OB_005174 Homo sapiens PARP1 142 The PARP1 enzyme catalyses the transfer of ADP-ribose to a variety of nuclear proteins including members of the high mobility group box and topoisomerase families [[PubMed icon] 3103132]. It is involved in a variety of processes such as proliferation, differentiation, and recovery from DNA damage [[PubMed icon] 12470832]. PARP1's levels appear to inversely correlate with mammalian lifespan and PARP1 has been hinted as a determinant of mammalian ageing [[PubMed icon] 1465394]. Nonetheless, more detailed studies are necessary to investigate these claims. 1465394, 3103132, 12470832 [GenAge icon]GenAge
90 OB_005175 Homo sapiens ATP5O 539 ATP5O is a mitochondrial protein, part of the proton-transporting complex. It has been linked to ageing in lower organisms. In roundworms, lowering the activity of an ATP5O homologue during larval stages, but not during adulthood, extends lifespan [[PubMed icon] 12471266]. Its involvement in mammalian ageing, however, is not known. 12471266 [GenAge icon]GenAge
91 OB_005176 Homo sapiens PCK1 5105 PCK1 is involved in the regulation of gluconeogenesis. Mice with PCK1 overexpressed in skeletal muscle were more active than controls and had an enhanced exercise capacity with an increased number of mitochondria. These mice ate more than controls, but had half the body weight and 10% the body fat. They were also reported to be long-lived [[PubMed icon] 17716967], though detailed ageing studies have not been conducted yet. 17716967 [GenAge icon]GenAge
92 OB_005177 Homo sapiens PCMT1 5110 PCMT1 is involved in the repair and degradation of damaged proteins. Overexpression of a PCMT1 homologue in fruit flies extends lifespan in a temperature-dependent fashion [[PubMed icon] 11742076]. PCMT1-deficient mice die at about 42 days after birth, though without signs of premature ageing [[PubMed icon] 11279164]. Although an age-related accumulation of defective proteins has been suggested as a factor in ageing, further research is needed to assess PCMT1's role, if any, in mammalian ageing. 11279164, 11742076 [GenAge icon]GenAge
93 OB_005178 Homo sapiens PCNA 5111 PCNA is an important player in DNA replication and, probably, in DNA repair. It has been associated with pathways suspect of being involved in human ageing, and it interacts with WRN [[PubMed icon] 11348659]. PCNA levels have also been linked to cellular proliferation in aged rats [[PubMed icon] 9032755]. Therefore, it is possible that PCNA influences human ageing even though more detailed studies are necessary to prove such hypothesis. 9032755, 11348659 [GenAge icon]GenAge
94 OB_005179 Homo sapiens PDGFB 5155 PDGFB is a mitogen and oncogene involved in cell survival, development, and healing [[PubMed icon] 12668888]. Results from rats suggest it may be related to age-related changes in the heart [[PubMed icon] 11827927], and PDGF's anti-apoptotic signalling involves several pathways and genes that in turn have been associated with ageing [[PubMed icon] 10485711]. PDGFB's exact relevance to human ageing, however, is unknown. 10485711, 11827927, 12668888 [GenAge icon]GenAge
95 OB_005180 Homo sapiens PDGFRA 5156 The PDGFRA gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. PDGFRA binds PDGFB and thus may be related to age-related changes in the heart [[PubMed icon] 12668888]. With age, there is a decline in the PDGFRA levels of beta-cell in mice, accompanied by a reduction in beta-cell replication. The conditional inactivation of Pdgfra accelerates these changes, preventing neonatal beta-cell expansion and adult beta-cell regeneration. Similar results were observed in human beta-cells [[PubMed icon] 21993628]. Receptor tyrosine kinases have been found to be expressed in metastatic colon cancer [[PubMed icon] 7896447] and PDGFRA mutations were found in gastrointestinal [[PubMed icon] 15928335]. 7896447, 12668888, 15928335, 21993628 [GenAge icon]GenAge
96 OB_005181 Homo sapiens PDGFRB 5159 PDGFRB binds PDGFB and thus may be related to age-related changes in the heart [[PubMed icon] 12668888]. PDGFRB is also an important player in development [[PubMed icon] 8645566]. 8645566, 12668888 [GenAge icon]GenAge
97 OB_005182 Homo sapiens PDPK1 5170 PDPK1 phosphorylates and activates AKT1, among other proteins, and appears to play a role in signal transduction and development, maybe by mediating the activation of AKT1 by growth factors. The PDPK1 encodes three isoforms. In roundworms, PDPK1 has been associated with signals related to development and longevity [[PubMed icon] 9716402]. Mice without PDPK1 die at embryonic stages, though mice with low levels of PDPK1 are viable and fertile despite a small body size [[PubMed icon] 12110585]. 9716402, 12110585 [GenAge icon]GenAge
98 OB_005183 Homo sapiens PEX5 5830 A peroxisome receptor, PEX5 has been associated with genes and pathways previously related to ageing, such as ATM [[PubMed icon] 10567403]. An involvement in cellular senescence has also been suggested [[PubMed icon] 9288097]. Nonetheless, a direct role of PEX5 in human ageing has not been demonstrated. 9288097, 10567403 [GenAge icon]GenAge
99 OB_005184 Homo sapiens PIK3CA 5290 Phosphatidylinositol 3-kinase, catalytic subunit alpha (PIK3CA) is a gene which plays a role in activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Target of rapamycin (MTOR) is a downstream effector of phosphoinositide 3-kinase, and thus PIK3CA might be also involved in ageing. In mice, suppression of the activity of the p110alpha isoform of PIK3CA preserved cardiac function and prevented many age-associated changes in the heart [[PubMed icon] 19822807]. PIK3CA is an oncogene and has been implicated in several types of cancers. 19822807 [GenAge icon]GenAge
100 OB_005185 Homo sapiens PIK3CB 5291 PIK3CB is involved in the signal transduction of insulin (INS) and insulin-like pathways including the activation of the MAPK pathway [[PubMed icon] 11884591]. A homologue of PIK3CB, age-1, has been related to ageing in roundworms [[PubMed icon] 8700226]. Genotype combinations in the human PIK3CB and IGF1R genes have been related to plasma IGF1 levels and longevity [[PubMed icon] 12843179], though the elucidation of PIK3CB's role in ageing will require more detailed studies. 8700226, 11884591, 12843179 [GenAge icon]GenAge