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

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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:
101 ... 200 [previous icon] [next icon]
# Observation Stable ID Species Gene Symbol NCBI Gene ID Other Ageing Factor Name Description PubMed Source
101 OB_005186 Homo sapiens ATR 545 ATR is involved in DNA repair by activating checkpoint signalling during genotoxic stresses including the phosphorylation of ageing-related proteins such as BRCA1 and TP53. Together with ATM, ATR has been suggested to regulate TP53 and WRN [[PubMed icon] 12629512]. ATR disruption in mice results in embryonic lethality in homozygous animals while heterozygous mice develop normally but have increased tumour incidence [[PubMed icon] 10691732]. Deletion of ATR in young adult mice eliminates 80-90% of proliferating cells and results in several age-related phenotypes accompanied by a depletion of stem and progenitor cells and exhaustion of tissue renewal and homeostatic capacity [[PubMed icon] 18371340]. Patients with mutations affecting ATR develop Seckel syndrome, characterized by growth retardation, dwarfism, and mental retardation, clinical features often found in disorders involving impaired DNA-damage responses [[PubMed icon] 12640452]. A possible role in human ageing is plausible though further research is necessary to confirm this hypothesis. 10691732, 12629512, 12640452, 18371340 [GenAge icon]GenAge
102 OB_005187 Homo sapiens PIK3R1 5295 Together with PIK3CB, PIK3R1 is involved in insulin (INS) signalling and energy metabolism [[PubMed icon] 9988280]. Disruption of PIK3CB in mice results in death shortly after birth and impaired B cell development [[PubMed icon] 9888855]. Although PIK3CB has not been directly related to human ageing, PIK3CB may be associated with signalling pathways that impact on human ageing. 9888855, 9988280 [GenAge icon]GenAge
103 OB_005188 Homo sapiens PIN1 5300 Important for the regulation of mitosis and cell cycle progression, PIN1 is critical for TP53 function [[PubMed icon] 12397362]. Some results indicate that PIN1 plays a role in protecting against neurodegenerative diseases [[PubMed icon] 10391244], and PIN1 regulates APP processing, suggesting a possible role in Alzheimer's disease [[PubMed icon] 16554819]. Although PIN1 has not been directly related to ageing, it is a promising avenue of research, at least in relation to neurodegeneration. 10391244, 12397362, 16554819 [GenAge icon]GenAge
104 OB_005189 Homo sapiens PLAU 5328 PLAU is a protease that converts plasminogen to plasmin. It appears to affect murine ageing: its overexpression in the brain diminishes food consumption and extends longevity probably through a mechanism similar to caloric restriction [[PubMed icon] 9060969]. It is unclear at present whether PLAU affects human ageing, despite some evidence linking PLAU to age-related neurological diseases [[PubMed icon] 12898287]. 9060969, 12898287 [GenAge icon]GenAge
105 OB_005190 Homo sapiens PLCG2 5336 PLCG2 catalyzes the hydrolysis of phospholipids and is crucial in intracellular signalling [[PubMed icon] 12437926]. Clearly, PLCG2 is affected by ageing [[PubMed icon] 7723932], though it is unclear whether PLCG2 influences human ageing. 7723932, 12437926 [GenAge icon]GenAge
106 OB_005191 Homo sapiens PMCH 5367 PMCH is a cyclic neuropeptide that appears to be involved in a number of neuronal functions such as food intake [[PubMed icon] 8637571]. PMCH overexpression leads to obesity and insulin (INS) resistance [[PubMed icon] 11160162]. In contrast, PMCH null mice are resistant to ageing-associated increases in body weight and INS resistance [[PubMed icon] 16443777]. While it is dubious that PMCH is a major factor in ageing, it could play a role in some age-related changes. 8637571, 11160162, 16443777 [GenAge icon]GenAge
107 OB_005192 Homo sapiens PML 5371 The PML gene encodes a number of transcripts and can function as a transcription factor. It is likely oncogenic and may act as a tumour suppressor [[PubMed icon] 11832207]. PML also appears to control cell proliferation and cellular senescence [[PubMed icon] 12093737], though its role, if any, in human ageing is unknown. 11832207, 12093737 [GenAge icon]GenAge
108 OB_005193 Homo sapiens POLA1 5422 POLA1 is involved in DNA replication. In yeast, mutations in POLA1 reduce lifespan [[PubMed icon] 12024027]. Age-related changes in POLA1 induction have been shown in rats [[PubMed icon] 12425958]. Whether POLA1 is involved in human ageing remains to be determined. 12024027, 12425958 [GenAge icon]GenAge
109 OB_005194 Homo sapiens POLB 5423 POLB is involved in DNA maintenance, replication, and recombination. It appears to play a role in DNA repair and it interacts with WRN [[PubMed icon] 12665521]. In mice, POLB haploinsufficiency increases cancer risk with age. While lifespan is not significantly altered, haploinsufficient mice may exhibit an increase in age-related mortality [[PubMed icon] 16885342]. POLB's role, if any, in human ageing remains to be determined. 12665521, 16885342 [GenAge icon]GenAge
110 OB_005195 Homo sapiens POLD1 5424 POLD1 is mostly involved in DNA synthesis, and probably it also functions in DNA repair [[PubMed icon] 3335506]. Mice with a proofreading-deficient version of POLD1 have a higher cancer incidence [[PubMed icon] 12429860]. POLD1 has also been associated with WRN [[PubMed icon] 11279038]. There is no direct evidence linking POLD1 to human ageing, but it should be considered a suspect gene. 3335506, 11279038, 12429860 [GenAge icon]GenAge
111 OB_005196 Homo sapiens POLG 5428 POLG is involved in mitochondrial DNA replication and repair [[PubMed icon] 12806118]. Mice with a proof-reading-deficient version of POLG display signs of premature ageing starting at about 25 weeks of age [[PubMed icon] 15164064]. Although the exact molecular and cellular events responsible for such phenotype are not clear, they could involve the accumulation of mitochondrial DNA mutations and an increased apoptosis [[PubMed icon] 16020738]. In humans, mutations in POLG have been associated with CNS diseases [[PubMed icon] 11431686]. Further studies are necessary to determine whether POLG plays a role in human ageing. 11431686, 12806118, 15164064, 16020738 [GenAge icon]GenAge
112 OB_005197 Homo sapiens ABL1 25 An important player in cellular proliferation and development, ABL1 also acts as an oncogene [[PubMed icon] 10805805]. Some results indicate ABL1 might also be involved in DNA repair [[PubMed icon] 10391251]. Disruption of ABL1 in mice results in severe defects and animals die shortly after birth [[PubMed icon] 2065353]. Although its exact functions remain elusive, ABL1 has been argued to play a role in ageing due to its interaction with ageing-related genes, such as ATM, and its functions [[PubMed icon] 15655364]. 2065353, 10391251, 10805805, 15655364 [GenAge icon]GenAge
113 OB_005198 Homo sapiens BAK1 578 The BCL2 oncogene, is a potent suppressor of apoptosis under diverse conditions. BAK, a gene belonging to the BCL2 family, promotes cell death and counteracts the protection from apoptosis provided by BCL2 [[PubMed icon] 7715730] [[PubMed icon] 7715731]. Bak knockout mice showed reduced age-related apoptotic cell death of spiral ganglion neurons and hair cells in the cochlea, which in turn resulted in the prevention of age-related hearing loss [[PubMed icon] 19901338]. 7715730, 7715731, 19901338 [GenAge icon]GenAge
114 OB_005199 Homo sapiens PON1 5444 PON1 hydrolyzes toxic compounds and is associated with high-density lipoproteins. Mice without PON1 are more susceptible to some toxic agents and, when fed a high-fat, high-cholesterol diet, atherosclerosis [[PubMed icon] 9685159]. Allelic variants in the human PON1 gene have been linked to longevity [[PubMed icon] 12889841] and neurodegenerative diseases [[PubMed icon] 9739148]. A role in human ageing is possible even if unverified. 9685159, 9739148, 12889841 [GenAge icon]GenAge
115 OB_005200 Homo sapiens POU1F1 5449 The POU1F1 transcription factor is expressed in the pituitary where it regulates pituitary development and hormone expression. It activates growth hormone (GH1) and is involved in mammalian development. Snell dwarf mouse are a strain mutant for POU1F1 that live significantly longer than controls and show signs of ageing retardation [[PubMed icon] 11371619]. POU1F1 abnormalities have been reported in humans associated with lower levels of GH1, prolactin, and thyroid-stimulating hormone, but with little or no evidence of an impact on ageing [[PubMed icon] 10549301]. 10549301, 11371619 [GenAge icon]GenAge
116 OB_005201 Homo sapiens PPARA 5465 PPARA is a transcription factor that may be involved in the metabolic control of the expression of genes encoding fatty acid oxidation enzymes. Knockout mice have been reported to be protected from insulin (INS) resistance induced by high-fat diet [[PubMed icon] 17652964]. Certain age-related pathologies, such as heart disease, may be related to PPARA [[PubMed icon] 10839530], but it unclear whether PPARA is a major player in human ageing. 10839530, 17652964 [GenAge icon]GenAge
117 OB_005202 Homo sapiens PPARG 5468 Peroxisome proliferator-activated receptor (PPAR)gamma-2 is an important regulator of adipose tissue metabolism, insulin sensitivity and inflammatory response. Recent studies have identified klotho (KL) as a target gene for peroxisome proliferator-activated receptor-gamma (PPARg) [[PubMed icon] 18547997]. Mutant mice with a lowered expression of Pparg had a reduced lifespan compared to wild type [[PubMed icon] 19997628], however adipose tissue-specific PPARg heterozygous mice exhibited significant improvement in insulin sensitivity in skeletal muscle and showed an increased resistance to paraquat-induced oxidative stress. The level of PPARs (including PPARG) is reduced with age and caloric restriction in mice appears to prevent these alteration, suggesting common mechanisms [[PubMed icon] 17389764]. Mutations in PPARG may be one of the causes of type 2 insulin-resistant diabetes and hyptertension [[PubMed icon] 10622252] and a polymorphism of PPARG has been associated to early atherosclerosis [[PubMed icon] 15356014]. Defects in PPARG may also be associated with colon cancer [[PubMed icon] 10394368]. Genome-wide association studies have identified a paraoxonase Pro/Ala gene polyporphism which is associated to human longevity [[PubMed icon] 15236769]. 10394368, 10622252, 15236769, 15356014, 17389764, 18547997, 19997628 [GenAge icon]GenAge
118 OB_005203 Homo sapiens PPARGC1A 10891 PPARGC1A is a transcriptional coactivator that regulates and interacts with genes involved in energy metabolism [[PubMed icon] 14999129]. It may link external stimuli to the regulation of mitochondrial biogenesis. SIRT1 has been reported to be a functional regulator of PPARGC1A [[PubMed icon] 17347648]. In humans, PPARGC1A has been associated with cholesterol and obesity as well as age-related diseases like type 2 diabetes. 14999129, 17347648 [GenAge icon]GenAge
119 OB_005204 Homo sapiens PPM1D 8493 PPM1D is upregulated by p53 in response to a number of stresses, such as DNA damage, and behaves as an oncogene. PPM1D-null males, but interestingly not females, showed reduced longevity and body weight and some signs of premature ageing. IGF1 levels were higher in PPM1D-null males until about one year of age yet then declined faster than in controls. PPM1D-null mice were cancer resistant and had an augmented stress response following DNA damage [[PubMed icon] 16652371]. 16652371 [GenAge icon]GenAge
120 OB_005205 Homo sapiens PPP1CA 5499 PPP1CA is part of protein phosphatase 1 (PP1), which is involved in different cellular processes including cell division, protein synthesis, and synaptic plasticity. PP1 inhibition in mice was associated with prolonged memory, and old mice had preserved memory, which suggests that PP1, including PPP1CA, could play a role in cognitive ageing [[PubMed icon] 12198546]. PPP1CA cardiac-specific overexpression in mice resulted in premature heart failure [[PubMed icon] 12024026]. Further research is necessary to establish whether PPP1CA is related to human ageing. 12024026, 12198546 [GenAge icon]GenAge
121 OB_005206 Homo sapiens PRDX1 5052 PRDX1 is involved in redox regulation and possibly in intracellular signalling cascades. Mice lacking PRDX1 have a shorter longevity due to anaemia and cancer, though it is unclear whether these animals age faster [[PubMed icon] 12891360]. PRDX1 has not been directly associated with human ageing. 12891360 [GenAge icon]GenAge
122 OB_005207 Homo sapiens PRKCA 5578 PRKCA is a phorbol ester receptor involved in signal transduction. It appears to interact with many proteins, including some that have been related to ageing, such as LMNA and INSR. In the medfly, PRKCA levels are age-dependent [[PubMed icon] 9032752]. PRKCA has not been directly related to human ageing. 9032752 [GenAge icon]GenAge
123 OB_005208 Homo sapiens PRKCD 5580 Involved in the regulation of growth, apoptosis, and differentiation of a variety of cell types [[PubMed icon] 10381525], PRKCD may influence age-related changes at the CNS and immune system level [[PubMed icon] 12904329]. 10381525, 12904329 [GenAge icon]GenAge
124 OB_005209 Homo sapiens BAX 581 An important player in apoptosis, BAX encodes multiple transcripts and has been linked to development, cancer, and age-related changes in apoptosis [[PubMed icon] 9102310]. Inactivation of BAX in mice extended fertile potential and minimized age-related health problems, including bone and muscle loss, excess fat deposition, alopecia, cataracts, deafness, increased anxiety, and selective attention deficit. It did not extend lifespan [[PubMed icon] 17360389]. Changes in apoptotic proteins like BAX could also contribute to ageing-associated atrophy in the skeletal muscle of rats [[PubMed icon] 16567372]. It is not known how these processes are related to human ageing, but a role of BAX in human ageing is a possibility. 9102310, 16567372, 17360389 [GenAge icon]GenAge
125 OB_005210 Homo sapiens PRKDC 5591 PRKDC is involved in DNA repair and may modulate transcription [[PubMed icon] 7851793]. Evidence also suggests PRKDC may be involved in telomere biology [[PubMed icon] 12426399]. Because PRKDC has been associated with many pathways with genes likely to be involved in human ageing, such as WRN [[PubMed icon] 11889123], it is possible that PRKDC itself is involved in human ageing, though further research is necessary to investigate this hypothesis. 7851793, 11889123, 12426399 [GenAge icon]GenAge
126 OB_005211 Homo sapiens PROP1 5626 A transcription factor involved in hormonal regulation and development, PROP1 sits upstream of POU1F1 [[PubMed icon] 8612966]. The Ames dwarf, a mouse strain mutant for PROP1, is remarkably long-lived with some evidence of delayed ageing [[PubMed icon] 8900272]. On the other hand, PROP1 mutations in mice are strongly influenced by genetic background and can be lethal in some cases [[PubMed icon] 15459176]. Human mutations in PROP1 result in pituitary hormone deficiency, typically characterized by growth retardation. Although some individuals may be long-lived , it is not known to what extent and in what direction PROP1 mutations affect the human ageing process [[PubMed icon] 15621211]. 8612966, 8900272, 15459176, 15621211 [GenAge icon]GenAge
127 OB_005212 Homo sapiens PSEN1 5663 The PSEN1 gene has multiple transcriptional variants and its functions could include the cleavage of APP and notch receptor protein. PSEN1-null mice die shortly after birth [[PubMed icon] 9160754]. Inactivating PSEN1 in the postnatal forebrain reduced beta-amyloid generation with subtle cognitive deficits [[PubMed icon] 11567612]. Mutations in the human PSEN1 gene cause early-onset Alzheimer's disease [[PubMed icon] 10850703], though PSEN1's role in human ageing remains largely unknown. 9160754, 10850703, 11567612 [GenAge icon]GenAge
128 OB_005213 Homo sapiens PTEN 5728 PTEN is a tumour suppressor involved in cell cycle progression as an inhibitor of insulin (INS) signalling. In roundworms, a PTEN homologue has been related to development and longevity regulation through the INS-like pathway [[PubMed icon] 15637588]. The same gene has been shown to mediate nutrient-dependent cell cycle arrest and growth in the germline of roundworms [[PubMed icon] 16631584]. PTEN-null mice die at embryonic stages while heterozygous animals develop tumours [[PubMed icon] 9697695]. In mice lacking PTEN in oocytes the entire primordial follicle pool becomes activated and thus all primordial follicles become depleted in early adulthood causing premature ovarian failure [[PubMed icon] 18239123]. Mutations in the human PTEN gene have been associated with cancer [[PubMed icon] 9140396], and further studies are necessary to determine whether PTEN plays a role in human ageing. 9140396, 9697695, 15637588, 16631584, 18239123 [GenAge icon]GenAge
129 OB_005214 Homo sapiens PTGS2 5743 PTGS2 may play a role in inflammation. PTGS2-null mice developed severe nephropathy [[PubMed icon] 8521477] and female reproductive failures [[PubMed icon] 9346237]. Age-related changes in PTGS2 have been reported in various tissues in mice [[PubMed icon] 12529332]. PTGS2 has not been directly related to human ageing. 8521477, 9346237, 12529332 [GenAge icon]GenAge
130 OB_005215 Homo sapiens PTK2 5747 PTK2, also known as focal adhesion kinase (FAK), plays a role in the signal transduction of a number of pathways such as MAPK signalling, apoptosis, cellular proliferation, and cellular senescence [[PubMed icon] 12805241]. PTK2 deletion in the epidermis of mice suppresses tumour formation [[PubMed icon] 15601818]. Its role, if any, in human ageing is unknown, but PTK2 could potentially be involved in downstream signalling cascades related to ageing. 12805241, 15601818 [GenAge icon]GenAge
131 OB_005216 Homo sapiens PTK2B 2185 Involved in stress response and signal transduction, PTK2B is an important player in a variety of processes including the regulation of ion channels by calcium and MAPK signalling [[PubMed icon] 7544443]. PTK2B is a focal adhesion kinase (FAK), which could be involved in cellular senescence and apoptosis [[PubMed icon] 16523241]. Its role, if any, in human ageing is unknown, but PTK2B could potentially be involved in downstream signalling cascades related to ageing. 7544443, 16523241 [GenAge icon]GenAge
132 OB_005217 Homo sapiens PTPN1 5770 PTPN1 inhibits insulin (INS) signalling and plays a role in INS sensitivity and fuel metabolism. Mice lacking PTPN1 are protected from diet-induced obesity and have enhanced enhanced INS sensitivity [[PubMed icon] 10066179]. PTP1B negatively regulates leptin (LEP) signalling [[PubMed icon] 11970899]. PTPN1 may thus be related to certain age-associated pathologies such as obesity. 10066179, 11970899 [GenAge icon]GenAge
133 OB_005218 Homo sapiens PTPN11 5781 PTPN11 is a signalling protein that plays a role in the signal transduction of many receptors that have been associated with ageing, such as GHR [[PubMed icon] 15985475]. Mutations in PTPN11 cause Noonan syndrome, which is often characterized by growth impairment and a disturbance of GH1 secretion and IGF1 signalling, even though this disease is probably due to a gain-of-function mutation [[PubMed icon] 4025385]. It is unknown whether PTPN11 plays a role in human ageing, but it may play a role in its signalling cascade. 4025385, 15985475 [GenAge icon]GenAge
134 OB_005219 Homo sapiens PYCR1 5831 The PYCR1 gene encodes an enzyme that catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline. It appears that mutations in PYCR1 result in altered mitochondrial function and progeroid changes in connective tissues. Defects in the PYCR1 gene are the cause of cutis laxa autosomal recessive type 2B, a syndromal disorder characterized by the appearance of premature aging, wrinkled and lax skin with reduced elasticity, joint laxity, craniofacial dysmorphic features, intrauterine growth retardation with some degree of postnatal growth deficiency, and developmental delay. Homozygosity or compound heterozygosity for mutations in the PYCR1 gene were found In consanguineous families, in humans, and knockdown of the orthologous genes in Xenopus and zebrafish resulted in epidermal hypoplasia and blistering, accompanied by a massive increase of apoptosis [[PubMed icon] 19648921]. Further research is needed in order to fully understand the link between PYCR1 and human ageing. 19648921 [GenAge icon]GenAge
135 OB_005220 Homo sapiens BCL2 596 BCL2 is an important suppressor of apoptosis and an oncogene. Apart from cancer, it may be involved in neurodegenerative disorders [[PubMed icon] 9315450], and dendritic cell longevity in vivo has been reported to be controlled by BCL2 [[PubMed icon] 12218115]. BCL2 null mice die by six weeks of age with occurrence of grey hair though otherwise they do not appear to suffer from accelerated ageing [[PubMed icon] 8170972]. In addition, some researchers have argued that BCL2's role in apoptosis suggests an involvement of BCL2 in ageing [[PubMed icon] 9288026]. More detailed studies are necessary to investigate this possibility. 8170972, 9288026, 9315450, 12218115 [GenAge icon]GenAge
136 OB_005221 Homo sapiens RAD51 5888 Involved in DNA unwinding and repair [[PubMed icon] 12442171], RAD51 has been reported to be an important player in the cellular senescence of yeast [[PubMed icon] 10207108]. Disruption of RAD51 in mice results in embryonic lethality [[PubMed icon] 8692798]. Its role in mammalian ageing remains unknown. 8692798, 10207108, 12442171 [GenAge icon]GenAge
137 OB_005222 Homo sapiens RAD52 5893 RAD52 is involved in DNA repair and appears to interact with WRN [[PubMed icon] 12750383]. It has been reported to be an important player in the cellular senescence of yeast [[PubMed icon] 10207108]. Its role, if any, in mammalian ageing remains elusive. 10207108, 12750383 [GenAge icon]GenAge
138 OB_005223 Homo sapiens RAE1 8480 In yeast, RAE1 is involved in RNA export. Probably, RAE1 is involved in nucleocytoplasmic transport. The RAE1 gene encodes different isoforms. Haploinsufficiency of both RAE1 and BUB3 in mice, but not haploinsufficiency of either gene by itself, reduces lifespan and appears to accelerate ageing [[PubMed icon] 16476774]. RAE1-null mice are embryonic lethal [[PubMed icon] 12551952]. 12551952, 16476774 [GenAge icon]GenAge
139 OB_005224 Homo sapiens RB1 5925 RB1 is a tumour suppressor that acts as a transcriptional regulator to control cell cycle progression. Mice with disrupted RB1 are not viable [[PubMed icon] 1406932]. Mutations in the human RB1 gene have been associated with cancer [[PubMed icon] 2594029]. Clearly, RB1 plays a role in cellular senescence and oncogenesis [[PubMed icon] 6320372], but it is unknown whether it influences human ageing. 1406932, 2594029, 6320372 [GenAge icon]GenAge
140 OB_005225 Homo sapiens RECQL4 9401 A helicase that has been associated with Rothmund-Thomson syndrome [[PubMed icon] 10552928], RECQL4 belongs to the same family of WRN and BLM. Though Rothmund-Thomson syndrome does not resemble accelerated ageing like Werner's syndrome does [[PubMed icon] 12200042], it is reasonable that RECQL4 might be involved in human ageing. RECQL4-deficient mice die at embryonic stages [[PubMed icon] 12915449]. 10552928, 12200042, 12915449 [GenAge icon]GenAge
141 OB_005226 Homo sapiens RELA 5970 Also known as NFKB3, RELA 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, but the NF-kappa-B complex appears to be important in age-related changes in inflammation and maybe in other age-related processes too [[PubMed icon] 12380689]. In addition, age-related changes in NF-kappa-B have been reported in numerous tissues [[PubMed icon] 12020944]. Mice without RELA die at embryonic stages [[PubMed icon] 7603567]. 7603567, 12020944, 12380689 [GenAge icon]GenAge
142 OB_005227 Homo sapiens RET 5979 A receptor tyrosine kinase that is also considered an oncogene, RET promotes cellular growth. Its levels increase with age in the nervous system [[PubMed icon] 10398293], and it has been related to cancer, but at present there is no evidence to suggest it plays a major role in human ageing. 10398293 [GenAge icon]GenAge
143 OB_005228 Homo sapiens RFC4 5984 Though its functions are still unclear, it appears that RFC4 is involved in DNA repair in association with ageing-related proteins, such as ATM and BRCA1 [[PubMed icon] 10783165]. RFC4 has not been directly related to ageing, though. 10783165 [GenAge icon]GenAge
144 OB_005229 Homo sapiens RGN 9104 RGN is mostly expressed in the liver, yet its functions remain obscure [[PubMed icon] 10360682]. Its expression levels decline with age, and RGN has been linked to age-related changes in calcium signalling in the liver of rats [[PubMed icon] 8794449]. RGN-null mice show susceptibility to TNF- and FAS-mediated apoptosis [[PubMed icon] 12368201] and increased oxidative stress in brain [[PubMed icon] 16500693]. A role for RGN in human ageing remains to be determined. 8794449, 10360682, 12368201, 16500693 [GenAge icon]GenAge
145 OB_005230 Homo sapiens RPA1 6117 RPA1 is involved in replication, recombination, and DNA repair. Due to its involvement with ageing-related genes, such as WRN [[PubMed icon] 10373438], RPA1 has been hinted as a player in the ageing process. Nonetheless, there is no direct evidence that RPA1 is linked to human ageing. 10373438 [GenAge icon]GenAge
146 OB_005231 Homo sapiens BDNF 627 BDNF is a growth factor that promotes neuronal survival and is involved in numerous neuronal responses. Mice with an accelerated postnatal rise in BDNF showed a precocious development of some CNS features [[PubMed icon] 10499792]. BDNF-deficient mice showed normal levels of serotonergic neurons at an early age but premature age-associated decrements [[PubMed icon] 10611369]. Polymorphisms in the human BDNF gene have been associated with memory and hippocampal function [[PubMed icon] 12553913]. Age-related changes in BDNF have also been reported in rats [[PubMed icon] 15837123]. In rats, BDNF has also been associated with changes in the heart [[PubMed icon] 16352696]. Although it is plausible that BDNF plays a role in some age-related pathologies, such as neurodegenerative diseases, its impact on human ageing has not been elucidated. 10499792, 10611369, 12553913, 15837123, 16352696 [GenAge icon]GenAge
147 OB_005232 Homo sapiens S100B 6285 S100B is mostly expressed in glial cells where it controls neuronal and glial cell proliferation. Its expression levels change with age [[PubMed icon] 10675765] and in Alzheimer's disease [[PubMed icon] 11578776]. Mice overexpressing the human S100B show pathological changes in their brains [[PubMed icon] 15126113]. S100B may thus be involved in neurodegenerative disorders, but there is no evidence at present that S100B plays a major role in human ageing. 10675765, 11578776, 15126113 [GenAge icon]GenAge
148 OB_005233 Homo sapiens SDHC 6391 A member of the mitochondrial electron transport chain, SDHC homologues have been implicated in ageing of lower life forms. In roundworms, mutations in a SDHC homologue have been reported to cause oxidative stress and premature ageing [[PubMed icon] 9716135]. Mutations in the human SDHC gene have been associated with mitochondrial respiratory chain deficiency [[PubMed icon] 7550341], but not with premature ageing. Whether SDHC influences human ageing has not been determined. 7550341, 9716135 [GenAge icon]GenAge
149 OB_005234 Homo sapiens SHC1 6464 SHC1 encodes three splice variants: p46, p52, and p66. Mice double-mutant for p66 live 30% longer though it is not clear whether they age slower [[PubMed icon] 10580504]. Although the exact functions of SHC1 remain unknown, it appears to play a role in the regulation of intra-cellular redox levels, signal transduction, and apoptosis [[PubMed icon] 11884717]. It may also be involved in stress response. Studies in humans have so far failed to associate polymorphisms in the SHC1 gene with ageing or longevity [[PubMed icon] 14530863]. 10580504, 11884717, 14530863 [GenAge icon]GenAge
150 OB_005235 Homo sapiens SIN3A 25942 SIN3A is a transcriptional regulator that interacts with MXI1 to antagonize MYC [[PubMed icon] 7889570]. Neuronal apoptosis has been related to elevated SIN3A levels [[PubMed icon] 9813182], though SIN3A expression levels did not increase with age in rats [[PubMed icon] 10964686]. SIN3A has not been directly related to human ageing. 7889570, 9813182, 10964686 [GenAge icon]GenAge
151 OB_005236 Homo sapiens SIRT1 23411 SIRT1 is a NAD-dependent deacetylase, which has the ability to regulate a number of processes by deacetylating key proteins, such as TP53 [[PubMed icon] 12006491]. In yeast, the SIRT1 homologue sir2 has been linked to cellular senescence [[PubMed icon] 10521401]. Increasing the levels of SIRT1 homologues in fruit flies [[PubMed icon] 15520384] and roundworms [[PubMed icon] 11242085] extends lifespan. SIRT1-null mice are born smaller than controls with evidence of developmental retardation. Depending on their genetic background, SIRT1-null mice either die shortly after birth or reach adulthood, the latter being smaller than controls and sterile [[PubMed icon] 12482959]. Heterozygous mice had a normal average lifespan [[PubMed icon] 18590691]. SIRT1 is overexpressed in calorie restricted rats, a response attenuated by insulin (INS) and IGF1 [[PubMed icon] 15205477]. Increased dosage of SIRT1 in pancreatic beta cells enhanced INS secretion [[PubMed icon] 16098828]. Mice with moderate overexpression of SIRT1 exhibit fat mass gain similar to controls exposed to a high-fat diet [[PubMed icon] 18599449]. Cardiac-specific low to moderate overexpression of SIRT1 attenuated age-dependent increases in cardiac hypertrophy, apoptosis, and expression of senescent biomarkers while a high level of overexpression had detrimental effects and induced cardiomyopathy [[PubMed icon] 17446436]. Although SIRT1 could impact on age-related diseases, such as type 2 diabetes, further studies are needed to establish its role in human ageing. 10521401, 11242085, 12006491, 12482959, 15205477, 15520384, 16098828, 17446436, 18590691, 18599449 [GenAge icon]GenAge
152 OB_005237 Homo sapiens SIRT3 23410 The sirtuin 3 (SIRT3) is a member of the sirtuins, a family of proteins which promote longevity in many organisms, is localized in mitochondria and regulates mitochondrial function. In mice, knockout of Sirt3 resulted in a decreased oxygen consumption, an increased oxidative stress in skeletal muscle, JNK activation and impaired insulin signaling [[PubMed icon] 21873205]. Young Sirt3-deficient mice (8 weeks) showed signs of cardiac hypertrophy and interstitial fibrosis even though they appeared to have normal activity. In contrast, Sirt3-expressing Tg mice were protected by blocking the cardiac hypertrophic response. In cell cultures, these results were linked to decreased ROS levels due to activation of Foxo3a, MnSOD and Cat [[PubMed icon] 19652361]. In humans the variability of the SIRT3 gene and its increased expression has been linked to an extended lifespan [[PubMed icon] 15676284] [[PubMed icon] 14580859]. 14580859, 15676284, 19652361, 21873205 [GenAge icon]GenAge
153 OB_005238 Homo sapiens SIRT6 51548 In yeast, sirtuins regulate epigenetic gene silencing. SIRT6, a chromatin-associated protein, also appears to be involved in DNA repair. SIRT6-null mice are small, with low levels of IGF1, display evidence of genomic instability, and exhibit signs of premature ageing after 2-3 weeks [[PubMed icon] 16439206]. As such, it is possible that SIRT6 plays a role in human ageing. 16439206 [GenAge icon]GenAge
154 OB_005239 Homo sapiens SIRT7 51547 SIRT7 encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Although the functions of human sirtuins have not yet been determined, evidence from lower organisms suggest that sirtuins might be implicated in ageing. Homozygous Sirt7 mouse mutants showed various signs of aging-related changes and died prematurely (heterozygous mice had a normal phenotype). Mice develop kyphosis and lost subcutaneous fat early in life, and showed a general decrease in stress-resistance mechanisms. They develop cardiomyopathy and are characterized by extensive fibrosis, leading to an increase in collagen III accumulation [[PubMed icon] 18239138].  In humans, levels of SIRT7 expression are significantly increased in breast cancer [[PubMed icon] 17003781] and in human thyroid carcinoma [[PubMed icon] 11953824]. 11953824, 17003781, 18239138 [GenAge icon]GenAge
155 OB_005240 Homo sapiens SLC13A1 6561 SLC13A1, also known as NaS1, is one of the members of the solute carrier family (sodium/sulfate symporters) and has a role in mediating sulfate reabsorption in the kidney. This gene appears to be involved in kidney disease. Knockout NaS1 mice (Nas1 -/- ) were found to live longer and have less tumors in aged mice. Median lifespans was increased in both male and female mice when compared with wild type [[PubMed icon] 21651971]. Similar results were observed for orthologs of SLC13A1 in flies [[PubMed icon] 11118146] and worm [[PubMed icon] 12480943]. 11118146, 12480943, 21651971 [GenAge icon]GenAge
156 OB_005241 Homo sapiens SNCG 6623 SNCG is a member of the synuclein family of proteins which are believed to be involved in the pathogenesis of neurodegenerative diseases. SNCG also appears to regulate BUB1B [[PubMed icon] 16142440]. While SNCG has been linked to cancer and CNS development [[PubMed icon] 10048491], its role, if any, in human ageing is unknown. 10048491, 16142440 [GenAge icon]GenAge
157 OB_005242 Homo sapiens BLM 641 BLM is a helicase involved in DNA repair and replication. Although Bloom syndrome is not considered accelerated ageing, BLM and WRN belong to the same family of proteins. Therefore, it is possible, even if unproven, that BLM plays a role in human ageing [[PubMed icon] 12200042]. 12200042 [GenAge icon]GenAge
158 OB_005243 Homo sapiens SOCS2 8835 SOCS2 is a member of the suppressor of cytokine signaling (SOCS) family and is a cytokine-inducible negative regulator of cytokine receptor signaling through the JAK/STAT pathway. The SOCS2 protein interacts with IGF1 and GH receptors [[PubMed icon] 9727029] as a negative regulator of GH signaling [[PubMed icon] 10403376] [[PubMed icon] 15690087]. The lack of SOCS2 expression in the high-growth mouse increases plasma IGF1, and reduces plasma and pituitary GH levels. Mutant mice exhibited a reduced mean and maximal lifespan compared to wild type [[PubMed icon] 19424848]. SOCS2 is also involved in several types of cancer [[PubMed icon] 16707422] [[PubMed icon] 17651480] [[PubMed icon] 18627528]. 9727029, 10403376, 15690087, 16707422, 17651480, 18627528, 19424848 [GenAge icon]GenAge
159 OB_005244 Homo sapiens SOD1 6647 SOD1 is an antioxidant, the SOD form predominant in the cytoplasm. Results from invertebrates suggest a role for SOD1 in ageing. Overexpression of SOD1 and CAT in short-lived strains of fruit flies extends lifespan and appears to delay ageing [[PubMed icon] 8108730], but the same effects are not witnessed in long-lived strains [[PubMed icon] 12743125]. SOD1-null mice develop normally, do not show signs of premature ageing, but are vulnerable to motor neuron loss after axonal injury [[PubMed icon] 8673102]. Overexpression of human SOD1 in transgenic mice results in neurodegenerative changes [[PubMed icon] 11114261]. In humans, mutations in SOD1 have been associated with amyotrophic lateral sclerosis [[PubMed icon] 12060716]. A role for SOD1 in human ageing, while not impossible, remains to be determined. 8108730, 8673102, 11114261, 12060716, 12743125 [GenAge icon]GenAge
160 OB_005245 Homo sapiens SOD2 6648 SOD2 is an antioxidant, the mitochondrial form of SOD and an important defence against oxidative damage. Evidence from invertebrates suggests it may play a role in ageing. Overexpression of SOD2 in flies significantly extends lifespan [[PubMed icon] 12072463]. Mice without SOD2 are not viable [[PubMed icon] 7493016]. Reducing the activity of SOD2 in mice increases the levels of oxidative damage to DNA but does not affect lifespan [[PubMed icon] 14679299]. SOD2 overexpression in mice slightly increases lifespan [[PubMed icon] 17129739], while gene deletion in connective tissue only resulted in mutant mice with a reduced lifespan and premature onset of aging-related phenotypes such as weight loss, skin atrophy, kyphosis, osteoporosis and muscle degeneration [[PubMed icon] 21108731]. In the long-lived alphaMUPA mice strain, a reduced level of SOD2 gene expression and activity, was observed together with a maintaining capacity to produce high levels of SOD2 in response to the inflammatory stimulus [[PubMed icon] 16139868]. Polymorphisms in the human SOD2 gene have been associated with type 2 diabetes [[PubMed icon] 12624725] and cardiomyopathy [[PubMed icon] 10425186]. A longevity-associated polymorphism was observed for Ashkenazi males [[PubMed icon] 15621215], but not for Italian [[PubMed icon] 9887369] and Jordanian [[PubMed icon] 20003469] populations. Although it is possible that SOD2 plays a role in human ageing, further studies are needed to investigate this hypothesis. 7493016, 9887369, 10425186, 12072463, 12624725, 14679299, 15621215, 16139868, 17129739, 20003469, 21108731 [GenAge icon]GenAge
161 OB_005246 Homo sapiens SP1 6667 An important transcription factor, SP1 is involved in the regulation of many genes, including ageing-related genes such as WRN [[PubMed icon] 11896071]. Some results have linked SP1 disruption to Huntington's disease [[PubMed icon] 11988536]. SP1 is involved in so many processes that it is possible for SP1 to play some role in human ageing. 11896071, 11988536 [GenAge icon]GenAge
162 OB_005247 Homo sapiens SST 6750 Somatostatin is an important regulator of endocrine and nervous system function [[PubMed icon] 11780120]. It inhibits the release of GH1 probably through GHRH [[PubMed icon] 7904758]. Because its levels change with age, it is likely that age-related changes are affected or affect SST [[PubMed icon] 10499533], and a role for SST in Alzheimer's disease has also been proposed [[PubMed icon] 15778722]. 7904758, 10499533, 11780120, 15778722 [GenAge icon]GenAge
163 OB_005248 Homo sapiens SSTR3 6753 The somatostatin (SST) receptor SSTR3 may play a role in the involution of the human thymus and other age-related pathologies [[PubMed icon] 10499533]. It have been associated with melanoma [[PubMed icon] 12601018]. SSTR3 has not been directly related to ageing, but it could be part of signalling cascades related to ageing. 10499533, 12601018 [GenAge icon]GenAge
164 OB_005249 Homo sapiens STAT3 6774 Transcription factors like those of the STAT family are activated by growth factors and cytokines. Their roles in intracellular signalling pathways suggest factors such as STAT3 might be involved in ageing and/or age-related disease [[PubMed icon] 10817928]. STAT3 has been associated with age-related heart failure in mice [[PubMed icon] 14566054]. 10817928, 14566054 [GenAge icon]GenAge
165 OB_005250 Homo sapiens STAT5A 6776 Like STAT5B, STAT5A is an important player in the activation of transcription and intracellular signalling. Mice with disrupted STAT5A and STAT5B, though short-lived due to numerous other deficiencies, exhibit phenotypes similar to those observed in GHR knockout mice in that they are 20%-40% smaller than controls with signs of disrupted GH1 functions such as lower IGF1 levels [[PubMed icon] 9630227]. Its relation to other proteins that may be involved in ageing make STAT5A a promising subject of research in gerontology [[PubMed icon] 10817928], though it is not known whether it plays a role in human ageing. 9630227, 10817928 [GenAge icon]GenAge
166 OB_005251 Homo sapiens STAT5B 6777 STAT5B is an important player in the activation of transcription and intracellular signalling. Mice with disrupted STAT5B and STAT5A, though short-lived due to numerous other deficiencies, exhibit phenotypes similar to those observed in GHR knockout mice in that they are 20%-40% smaller than controls with signs of disrupted GH1 functions such as lower IGF1 levels [[PubMed icon] 9630227]. Its relation to other proteins that may be involved in ageing make STAT5B a possible, albeit unproven, player in human ageing and age-related disease [[PubMed icon] 10817928]. 9630227, 10817928 [GenAge icon]GenAge
167 OB_005252 Homo sapiens STK11 6794 The exact functions of STK11 are unknown, but it appears to be involved in TP53-related apoptosis [[PubMed icon] 11430832]. Evidence suggests it may play a role in development, and it is clear that STK11 is related to tumour development [[PubMed icon] 12060709]. STK11 has not been directly linked to human ageing. 11430832, 12060709 [GenAge icon]GenAge
168 OB_005253 Homo sapiens BMI1 648 BMI1 is an oncogene involved in transcriptional regulation by remodelling chromatin. It may also be involved in development. Overexpression of BMI1 in mice results in transformation of axial skeleton [[PubMed icon] 7715727]. BMI1-null mice show reduced self-renewal of neural stem cells [[PubMed icon] 12714971], and thus a role for BMI1 in stem cell senescence has been proposed [[PubMed icon] 14722607]. Whether BMI1 impacts on human ageing remains to be determined. 7715727, 12714971, 14722607 [GenAge icon]GenAge
169 OB_005254 Homo sapiens STUB1 10273 STUB1 is involved in proteasomal degradation by targeting misfolded chaperone substrates and interacting with chaperone complexes, including HSPA8, thus contributing to protein quality control. STUB1-null mice exhibit a deregulation of protein quality control. They have a short lifespan and accelerated age-related pathophysiological features [[PubMed icon] 18411298], suggesting a potential role of STUB1 in ageing. 18411298 [GenAge icon]GenAge
170 OB_005255 Homo sapiens SUMO1 7341 SUMO1 is a small protein that interacts with several partners and hence is related to many processes, including DNA repair and signal transduction. It may be related to WRN [[PubMed icon] 10806190]. There is no evidence associating SUMO1 with ageing, though because of its many functions it is possible that SUMO1 has some impact on human ageing. 10806190 [GenAge icon]GenAge
171 OB_005256 Homo sapiens SUN1 23353 Mutations in the LMNA gene result in Emery-Dreifuss muscular dystrophy (AD-EDMD) and the Hutchinson-Gilford progeroid syndrome (HGPS). Two mouse models, Lmna null (Lmna(-/-)) and progeroid Lmna delta9 have been created, displaying these two pathologies, with an accordingly shorten lifespan. In both cases, however, a deficiency in the Sun1 gene resulted in reduced tissue pathologies and enhanced longevity. Similarly, a reduction of SUN1 overaccumulation in LMNA mutant fibroblasts and in cells derived from HGPS patients corrected nuclear defects and cellular senescence [[PubMed icon] 22541428]. 22541428 [GenAge icon]GenAge
172 OB_005257 Homo sapiens TAF1 6872 Essential in cell cycle progression, TAF1 is also involved in transcription as part of the TFIID transcription factor together with TBP [[PubMed icon] 8450888]. There is no direct evidence linking TAF1 to human ageing, but due to TAF1's importance in cell cycle control and its relation with other proteins previously related to ageing, TAF1 might play some role in human ageing. 8450888 [GenAge icon]GenAge
173 OB_005258 Homo sapiens TBP 6908 TBP is part of the TFIID general transcription factor. Because of its central role in the activation of eukaryotic genes, TBP is potentially involved in a large variety of processes. TBP-null mice die at embryonic stages [[PubMed icon] 12411709]. Mutations in the human TBP gene have been associated with neurological diseases [[PubMed icon] 11313753]. Although TBP has not been directly linked to human ageing, because it is involved in so many different processes, and potentially in neurodegenerative diseases, it is possible that TBP plays some role in human ageing. 11313753, 12411709 [GenAge icon]GenAge
174 OB_005259 Homo sapiens TCF3 6929 A crucial protein in development, TCF3 may be involved in ageing of the immune system [[PubMed icon] 15882343]. 15882343 [GenAge icon]GenAge
175 OB_005260 Homo sapiens TERC 7012 The RNA component of telomerase, TERC is involved in elongating the telomeres and is a critical factor in cellular senescence [[PubMed icon] 7544491]. TERC disruption in mice shortens lifespan and increases tumour incidence but it does not appear to accelerate ageing [[PubMed icon] 10089885]. Late-generation mice with disrupted TERC, and hence with shorter telomeres, when combined with mutations in ATM [[PubMed icon] 12540856] or WRN [[PubMed icon] 15235603] may suffer from accelerated ageing. Telomere shortening in mice lacking TERC also appears to impact on the pathologies caused by mutations in BLM [[PubMed icon] 15367665]. Human mutations in TERC are a cause of dyskeratosis congenita, a skin and bone marrow failure syndrome which is not classified as accelerated ageing [[PubMed icon] 11574891]. 7544491, 10089885, 11574891, 12540856, 15235603, 15367665 [GenAge icon]GenAge
176 OB_005261 Homo sapiens TERF1 7013 TERF1 associates with the telomeres and appears to be an important regulator of telomere biology [[PubMed icon] 10669743]. Its role in human ageing is unknown. 10669743 [GenAge icon]GenAge
177 OB_005262 Homo sapiens TERF2 7014 Together with TERF1, TERF2 appears to play an important role in telomere biology [[PubMed icon] 10669743]. Despite its association with WRN [[PubMed icon] 14712220], TERF2's role in human ageing is unknown. 10669743, 14712220 [GenAge icon]GenAge
178 OB_005263 Homo sapiens TERT 7015 Telomerase repairs/elongates the telomeres and is crucial in cellular proliferation. TERT expression is sufficient to overcome cellular senescence in culture [[PubMed icon] 9454332], but overexpression of TERT in mice does not extend longevity [[PubMed icon] 11387197]. Most human cell lines have low or insignificant levels of TERT while cancer cells often have high levels [[PubMed icon] 11850781]. In humans, mutations in TERT have been linked to aplastic anaemia [[PubMed icon] 15814878]. As such, TERT appears to be an important player in cellular proliferation, even if its relation to human ageing remains obscure. 9454332, 11387197, 11850781, 15814878 [GenAge icon]GenAge
179 OB_005264 Homo sapiens BRCA1 672 BRCA1 is crucial in cellular responses to DNA damage and may also be a transcriptional regulator. It interacts with WRN [[PubMed icon] 16714450]. Mutations in BRCA1 result in embryonic lethality in mice and humans. Mice hypomorphic for BRCA1 and heterozygous for TP53 have slower growth rates and display signs of premature ageing starting at about 8 months of age [[PubMed icon] 12533509]. Loss or haploid loss of CHEK2 also enables mice lacking BRCA1 to avoid embryonic lethality and display signs of premature ageing at about 18 months of age and develop multiple tumours later in life [[PubMed icon] 16675955]. In humans, some evidence suggests differences in BRCA1 genotype frequencies between centenarians and controls [[PubMed icon] 11795532]. BRCA1's role in cancer in humans is undisputed [[PubMed icon] 9353177], and it is possible it also plays a role in ageing. 9353177, 11795532, 12533509, 16675955, 16714450 [GenAge icon]GenAge
180 OB_005265 Homo sapiens TFAP2A 7020 TFAP2A is a transcription factor involved in a variety of processes, including development and morphogenesis. Disruption of TFAP2A results in multiple developmental defects and death at birth [[PubMed icon] 8622765]. Due to its association with WRN and other helicases [[PubMed icon] 11896071], it is possible, though unproven, that TFAP2A plays some role in human ageing. 8622765, 11896071 [GenAge icon]GenAge
181 OB_005266 Homo sapiens TFDP1 7027 TFDP1 is a transcription factor that may play a role in cell cycle regulation and apoptosis [[PubMed icon] 1710781]. Despite its association with cellular senescence [[PubMed icon] 15716376], TFDP1 has not been directly linked to organismal ageing. 1710781, 15716376 [GenAge icon]GenAge
182 OB_005267 Homo sapiens TGFB1 7040 TGFB1 is an important growth factor in development and differentiation. Some evidence suggests TGFB1 is involved in the response to oxidative stress [[PubMed icon] 12419465]. In roundworms, it has been argued that a TGFB signalling pathway acts downstream of other signals to repress body size and lifespan [[PubMed icon] 12571101]. Mutations in TGFB1 have been linked to several pathologies in humans [[PubMed icon] 10793168], and a polymorphism in this gene has been associated with human longevity [[PubMed icon] 15569360]. Nonetheless, it is unclear if/how TGFB1 influences human ageing. 10793168, 12419465, 12571101, 15569360 [GenAge icon]GenAge
183 OB_005268 Homo sapiens TNF 7124 A cytokine involved in the immune response, TNF can induce cell death in some tumour cells. It can also induce cellular proliferation and differentiation [[PubMed icon] 9223320]. TNF-deficient mice develop normally but are more susceptible to some infectious agents [[PubMed icon] 9223320]. Other results from mice suggest that TNF may protect neurons by stimulating antioxidant pathways [[PubMed icon] 8673925]. There is an association between TNF levels and age [[PubMed icon] 11405390], though human polymorphisms in TNF have not been associated with longevity [[PubMed icon] 11640949]. Although TNF may be associated with human age-related diseases, such as dementia [[PubMed icon] 15271127], more studies are necessary to establish what is TNF's involvement in human ageing. 8673925, 9223320, 11405390, 11640949, 15271127 [GenAge icon]GenAge
184 OB_005269 Homo sapiens TOP1 7150 Topoisomerases regulate the topological states of DNA. Though no direct interaction has been reported, TOP1 has been indirectly linked to WRN [[PubMed icon] 14612507]. TOP1 may also be important in the regulation of various brain functions and its activity is age-dependent [[PubMed icon] 16261531]. Because TOP1 has been associated with several DNA metabolism proteins thought to play a role in ageing, it is possible that TOP1 is itself involved in human ageing, though further studies are necessary to confirm this hypothesis. 14612507, 16261531 [GenAge icon]GenAge
185 OB_005270 Homo sapiens TOP2A 7153 Topoisomerases regulate the topological states of DNA [[PubMed icon] 7980433]. Though no direct interaction has been reported, TOP2A has been indirectly linked to WRN [[PubMed icon] 10725663] and ATM [[PubMed icon] 2836804]. TOP2A has also been suggested as an important player in neuron proliferation [[PubMed icon] 7980433]. Because TOP2A has been associated with several DNA metabolism proteins thought to play a role in ageing, it is possible that TOP2A itself is involved in human ageing, though further studies are necessary to confirm this hypothesis. 2836804, 7980433, 10725663 [GenAge icon]GenAge
186 OB_005271 Homo sapiens TOP2B 7155 Topoisomerases regulate the topological states of DNA [[PubMed icon] 7980433]. Though no direct interaction has been reported, TOP2B has been indirectly linked to WRN [[PubMed icon] 10725663] and ATM [[PubMed icon] 2836804]. TOP2B has also been suggested as an important player in neuron proliferation [[PubMed icon] 7980433]. Because TOP2B has been associated with several DNA metabolism proteins thought to play a role in ageing, it is possible that TOP2B is itself involved in human ageing, though further studies are necessary to confirm this hypothesis. 2836804, 7980433, 10725663 [GenAge icon]GenAge
187 OB_005272 Homo sapiens TOP3B 8940 TOP3B affects the supercoiling of the DNA. Mice lacking TOP3B develop normally but have a shorter lifespan. It is unclear whether these animals age faster [[PubMed icon] 11331780]. Litter size decreases over time and through successive generations in TOP3B-null mice, probably due to embryonic death [[PubMed icon] 12591952]. A role for TOP3B in human ageing remains to be determined. 11331780, 12591952 [GenAge icon]GenAge
188 OB_005273 Homo sapiens TOPORS 10210 TOPORS is an E3 ubiquitin-protein ligase and an E3 SUMO1-protein ligase, which acts as a tumor suppressor and is involved in cell growth, cell proliferation and apoptosis, regulating p53 stability through ubiquitin-dependent degradation [[PubMed icon] 15735665]. Homozygote knockout mice exhibited a significantly reduced lifespan, while a slight reduction in lifespan was observed for the heterozygote knockout. Several mice showed some signs of premature aging, including kyphosis, and a high incidence of multiple forms of cancer tumors [[PubMed icon] 20429939]. 15735665, 20429939 [GenAge icon]GenAge
189 OB_005274 Homo sapiens TP53 7157 TP53 is a tumour suppressor involved in cell cycle regulation, apoptosis, and DNA repair [[PubMed icon] 8654922]. Several lines of evidence from model organisms link TP53 to ageing. In flies, expression of a dominant-negative version of TP53 extends lifespan [[PubMed icon] 16303568]. Mice with an activated TP53 display signs of premature ageing starting at about 18 months of age [[PubMed icon] 11780111], as do mice heterozygous for TP53 and without BRCA1 [[PubMed icon] 12533509]. Human mutations in TP53 have been associated with cancer [[PubMed icon] 9218725]. People with a polymorphism that decreases the apoptotic potential of TP53 have increased survival despite a higher proportional mortality from cancer [[PubMed icon] 15732191]. The myriad of functions and interactions of TP53, as well as the findings from model organisms, make it a possible player in human ageing. 8654922, 9218725, 11780111, 12533509, 15732191, 16303568 [GenAge icon]GenAge
190 OB_005275 Homo sapiens BRCA2 675 BRCA2 is an important protein in cellular responses to DNA damage and may be directly involved in DNA repair. Mice deficient for BRCA2 have a reduced lifespan, though it is not clear whether they age faster [[PubMed icon] 12619154]. Although BRCA2's role in cancer is clear [[PubMed icon] 8524414], elucidating its role in human ageing will require additional studies. 8524414, 12619154 [GenAge icon]GenAge
191 OB_005276 Homo sapiens TP53BP1 7158 BRCA1 plays an important role in DNA repair, cell cycle checkpoint control, maintaining genomic stability and acts as a tumor suppressor. BRCA1 mouse mutants result in embryonic lethality and hypomorphic BRCA1 mice and heterozygous for TP53 have slower growth rates and display signs of premature ageing [[PubMed icon] 12533509]. These phenotypes are almost completely reverted in double knockout mice, lacking TP53BP1. The mutant mice showed an almost normal lifespan and also displayed a relative absence of various progeriod phenotypes, even though high levels of genomic instability were still observed [[PubMed icon] 19716796]. In humans, TP53BP1 in implicated in various forms of cancer [[PubMed icon] 17522062] [[PubMed icon] 17546051] [[PubMed icon] 18804090] [[PubMed icon] 19422301] [[PubMed icon] 20453858]. 12533509, 17522062, 17546051, 18804090, 19422301, 19716796, 20453858 [GenAge icon]GenAge
192 OB_005277 Homo sapiens TP63 8626 TP63 is a homologue of TP53 that plays a role in development and oncogenesis by regulating proliferation and differentiation [[PubMed icon] 10227293]. This gene encodes several isoforms whose expression differs between tissues. TP63-null mice have major developmental defects [[PubMed icon] 10227294]. Heterozygous TP63 mice have a reduced lifespan (over 20% shorter than controls) and exhibit signs of premature ageing [[PubMed icon] 16107615]. Mutations in TP63 in humans have been associated with several disorders, including EEC which is characterized by ectrodactyly, ectodermal dysplasia, and facial clefts [[PubMed icon] 10535733]. Corneal dystrophy and premature menopause have also been associated with a mutation in TP63 [[PubMed icon] 17609671]. 10227293, 10227294, 10535733, 16107615, 17609671 [GenAge icon]GenAge
193 OB_005278 Homo sapiens TP73 7161 The tumor suppressor TP73 encodes a member of the p53 family of transcription factors involved in cellular responses to stress and developmentand participates in the apoptotic response to DNA damage. Compared to p53-deficient mice, the p73-deficient mice also exhibited profound defects, including hippocampal dysgenesis, hydrocephalus, chronic infections and inflammation, as well as abnormalities in pheromone sensory pathways, but showed no increased susceptibility to spontaneous tumorigenesis [[PubMed icon] 10716451]. Old p73 +/- mice are more susceptible to neurodegeneration and showed decreased cognitive and motor function, brain atrophy, and neuronal degeneration compared to wild type [[PubMed icon] 18786355]. Mice lacking one of the isoforms (DeltaNp73) are viable and fertile but display the signs of neurodegeneration. Cells from these mice are more sensible to DNA-damage and have an increased p53-dependent apoptosis [[PubMed icon] 20194434]. 10716451, 18786355, 20194434 [GenAge icon]GenAge
194 OB_005279 Homo sapiens TPP2 7174 Knockout in mice resulted in viable animals which are almost indistinguishable from their wild type littermates when young. After the age of 1 year mutant mice show an increased mortality and multiple signs of premature ageing. They exhibt an aged appearance, disheveled fur, large bald areas, reduced body mass, and loss of vigor. Mice also show symptoms characteristic of immunohematopoietic senescence, including accelerated thymic involution, lymphopenia, impaired proliferative T cell responses, extramedullary hematopoiesis, and inflammation. Premature cellular senescence in fibroblasts, coinciding with the upregulation of p53 and the dysregulation of Nfkb1 was also observed [[PubMed icon] 18362329]. In human embryonic kidney cells overexpression of TPP2 induces accelerated growth and resistance to apoptosis, correlated with the appearance of multiple chromosomal aberrations, numerical and structural centrosome abnormalities, and multipolar cell divisions, suggesting a role in the regulation of centrosome homeostasis and mitotic fidelity [[PubMed icon] 15735022]. 15735022, 18362329 [GenAge icon]GenAge
195 OB_005280 Homo sapiens TXN 7295 TXN plays a role in regulating the cellular redox status. Some evidence also indicates TXN is a growth-suppressor [[PubMed icon] 14580311]. TXN overexpression in the neurons of flies extended the mean lifespan by 15% [[PubMed icon] 17301052]. Its overexpression in mice increases lifespan, but it is not known whether the ageing process is affected [[PubMed icon] 12230882]. More detailed studies are necessary. 12230882, 14580311, 17301052 [GenAge icon]GenAge
196 OB_005281 Homo sapiens UBB 7314 UBB is involved in the regulation of chromatin structure and stress response, as well as in the degradation of cellular proteins [[PubMed icon] 3029682]. In lower life forms, such as invertebrates, stress-response proteins similar to UBB have been associated with ageing. UBB has also been associated with neurodegenerative diseases [[PubMed icon] 12200043]. Although unproven, a role for UBB in ageing and/or age-related diseases is possible. 3029682, 12200043 [GenAge icon]GenAge
197 OB_005282 Homo sapiens UBE2I 7329 UBE2I catalyzes the attachment of SUMO1 to other proteins. Although no direct evidence exists to suggest a role for UBE2I in ageing, it is related to, among others, WRN [[PubMed icon] 10806190] and PCNA [[PubMed icon] 12226657], suggesting it might play a role in DNA repair and perhaps even in ageing. UBE2I deficiency in mice results in embryonic lethality [[PubMed icon] 16326389]. 10806190, 12226657, 16326389 [GenAge icon]GenAge
198 OB_005283 Homo sapiens UCHL1 7345 UCHL1 has both ligase and hydrolase activities [[PubMed icon] 2530630], and it may be involved in protein degradation. Results from lower life forms implicate similar stress-response proteins in ageing. In humans, there is evidence linking UCHL1 mutations to Parkinson's disease [[PubMed icon] 9774100]. Brain ageing and neurodegenerative diseases in humans have also been associated with the progressive accumulation of ubiquitinated protein conjugates, which are pathologically similar to the degeneration found in mice with disrupted UCHL1 [[PubMed icon] 3340629]. Nonetheless, it is unclear whether UCHL1 is related to human ageing. 2530630, 3340629, 9774100 [GenAge icon]GenAge
199 OB_005284 Homo sapiens UCP1 7350 Mitochondrial uncoupling proteins create proton leaks across the inner mitochondrial membrane to uncouple oxidative phosphorylation from ATP synthesis resulting in energy being dissipated as heat. Mice with skeletal muscle-specific UCP1 expression had increased median survival, decreased adiposity, increased temperature and metabolic rate. The same genetic manipulation in APOE null mice decreased diet-induced atherosclerosis and in agouti yellow mice, a model of obesity, diabetes and hypertension were reversed [[PubMed icon] 18054318]. 18054318 [GenAge icon]GenAge
200 OB_005285 Homo sapiens UCP2 7351 Mitochondrial uncoupling proteins create proton leaks across the inner mitochondrial membrane to uncouple oxidative phosphorylation from ATP synthesis resulting in energy being dissipated as heat. Like similar proteins, UCP2 appears thus to be involved in thermogenesis. In the fruit fly, overexpression of human UCP2 in adult neurons decreases oxidative damage and extends lifespan [[PubMed icon] 16054055]. UCP2-null mice had increased glucose-stimulated insulin (INS) secretion [[PubMed icon] 11440717]. Transgenic mice overexpressing UCP2 in hypocretin neurons have an elevated hypothalamic temperature which results in reduction of the core body temperature. These animals had increased energy efficiency and a greater median lifespan [[PubMed icon] 17082459]. In humans, UCP2 polymorphisms have been linked to obesity [[PubMed icon] 11381268]. 11381268, 11440717, 16054055, 17082459 [GenAge icon]GenAge