)| PMID |
16227974 ( ) |
|---|---|
| Title | Radical medicine: treating ageing to cure disease. |
| Abstract | The incidence of many diseases rises sharply with age. Although clearly separable, ageing and certain age-related diseases might share common mechanisms. Cellular metabolism and subsequent generation of reactive oxygen species might contribute both to the rate at which we age and to our susceptibility to numerous chronic diseases, therefore therapies that directly target the ageing process might provide new ways to treat human diseases. National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892, USA. finkelt@nih.gov |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 10840 | SHC1 | SHC (Src homology 2 domain containing) transforming protein 1 | 8 | SHC | p66Shc | p66SHC | p66 | |
| 2859 | DHCR24 | 24-dehydrocholesterol reductase | 7 | seladin-1 | seladin 1 | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 6 | APP | amyloid | |
| 14929 | SIRT1 | sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae) | 5 | SIRT1 | |
| 10886 | SIRT2 | sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae) | 5 | SIR-2 | Sir2 | |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | 4 | superoxide dismutase 2 | Sod2 | |
| 11138 | SNCA | synuclein, alpha (non A4 component of amyloid precursor) | 4 | alpha synuclein | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 4 | SOD1 | superoxide dismutase | |
| 795 | ATM | ataxia telangiectasia mutated | 3 | ATM | ataxia telangiectasia mutated | |
| 118 | ACO2 | aconitase 2, mitochondrial | 3 | aconitase | |
| 14581 | PINK1 | PTEN induced putative kinase 1 | 3 | PINK1 | |
| 14931 | SIRT3 | sirtuin (silent mating type information regulation 2 homolog) 3 (S. cerevisiae) | 3 | SIRT3 | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 3 | nadph oxidase | |
| 11998 | TP53 | tumor protein p53 | 2 | p53 | |
| 6206 | JUND | jun D proto-oncogene | 2 | JunD | |
| 9588 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 1 | PTEN-induced | |
| 380 | AKR1A1 | aldo-keto reductase family 1, member A1 (aldehyde reductase) | 1 | alcohol dehydrogenase | |
| 11283 | SRC | v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) | 1 | Src-homology-2-containing | |
| 7553 | MYC | v-myc myelocytomatosis viral oncogene homolog (avian) | 1 | Myc | |
| 6876 | MAPK14 | mitogen-activated protein kinase 14 | 1 | p38 | |
| 6881 | MAPK8 | mitogen-activated protein kinase 8 | 1 | JNKs | |
| 12468 | UBC | ubiquitin C | 1 | ubiquitin c | |
| 18985 | DCXR | dicarbonyl/L-xylulose reductase | 1 | carbonyl reductase | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.4 | the cytosolic form of the antioxidant protein superoxide dismutase ( SOD1 1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.4 | That said how disease-causing mutations in SOD1 lead to ALS remains controversial 2 3 |
| 14581 | PINK1 | PTEN induced putative kinase 1 | PINK1 | 0.6 | alpha-synuclein parkin ubiquitin C-terminal hydrolase-1 DJ1 and PTEN-induced kinase-1 ( PINK1 (Refs Refs 2 4 |
| 9588 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | PTEN-induced | 0.1 | including those encoding alpha-synuclein parkin ubiquitin C-terminal hydrolase-1 DJ1 and PTEN-induced kinase-1 ( PINK1 (Refs Refs 2 4 |
| 14581 | PINK1 | PTEN induced putative kinase 1 | PINK1 | 0.6 | Finally PINK1 has a mitochondrial-targeting sequence and in this subcellular location it |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | characteristic feature of Alzheimer's disease is the formation of extracellular amyloid plaques that contain cleavage products amyloid-beta (A A beta of |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | plaques that contain cleavage products amyloid-beta (A A beta of amyloid precursor protein ( APP |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.6 | products amyloid-beta (A A beta of amyloid precursor protein ( APP |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.6 | forms of Alzheimer's disease have been linked to mutations in APP or in gene products that are involved in APP processing |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.6 | in APP or in gene products that are involved in APP processing |
| 118 | ACO2 | aconitase 2, mitochondrial | aconitase | 2.1 | Studies with the mitochondrial protein aconitase have demonstrated that low levels of ROS caused mild oxidation |
| 118 | ACO2 | aconitase 2, mitochondrial | aconitase | 2.1 | oxidation and stimulated degradation whereas higher levels of ROS caused aconitase to aggregate and become more resistant to proteasomal degradation 20 |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | Sod2 | 1.7 | Superoxide dismutase-2 - Sod2 - mice which lack one copy of this mitochondrial antioxidant |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | Sod2 | 1.7 | protein peroxiredoxin-I (Ref Ref 32 or are heterozygous deleted for Sod2 (Ref Ref 33 have increased spontaneous tumour formation |
| 11998 | TP53 | tumor protein p53 | p53 | 0.3 | For example there is evidence that p53 Myc ataxia telangiectasia mutated ( ATM and Ras can all |
| 795 | ATM | ataxia telangiectasia mutated | ATM | 2.2 | there is evidence that p53 Myc ataxia telangiectasia mutated ( ATM and Ras can all alter intracellular ROS levels 31 |
| 7553 | MYC | v-myc myelocytomatosis viral oncogene homolog (avian) | Myc | 0.2 | For example there is evidence that p53 Myc ataxia telangiectasia mutated ( ATM and Ras can all alter |
| 2859 | DHCR24 | 24-dehydrocholesterol reductase | seladin-1 | 1.3 | Another group noted that inhibiting seladin-1 could also block Ras- or oxidant-induced senescence 42 (seladin-1 seladin-1 |
| 2859 | DHCR24 | 24-dehydrocholesterol reductase | seladin-1 | 1.3 | seladin-1 could also block Ras- or oxidant-induced senescence 42 (seladin-1 seladin-1 had been previously discovered in the context of Alzheimer's disease |
| 2859 | DHCR24 | 24-dehydrocholesterol reductase | seladin-1 | 1.3 | Notably following hydrogen-peroxide treatment seladin-1 translocates to the nucleus where it seems to bind to |
| 11998 | TP53 | tumor protein p53 | p53 | 0.3 | the nucleus where it seems to bind to and stabilize p53 |
| 6206 | JUND | jun D proto-oncogene | JunD | 0.3 | Recently the transcription factor JunD was shown to regulate the levels of tumour-secreted angiogenic growth |
| 10886 | SIRT2 | sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae) | SIR-2 | 1.3 | melanogaster and Caenorhabditis elegans overexpression of the NAD-dependent histone deacetylase SIR-2 results in an increased lifespan 48 49 |
| 10886 | SIRT2 | sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae) | SIR-2 | 1.3 | The closest mammalian orthologue of SIR-2 is SIRT1 and it is presently not known whether overexpression |
| 14929 | SIRT1 | sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae) | SIRT1 | 0.3 | The closest mammalian orthologue of SIR-2 is SIRT1 and it is presently not known whether overexpression of SIRT1 |
| 14929 | SIRT1 | sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae) | SIRT1 | 0.3 | SIRT1 and it is presently not known whether overexpression of SIRT1 will extend mammalian lifespan |
| 10886 | SIRT2 | sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae) | Sir2 | 1.3 | For instance yeast Sir2 seems to be important in protecting cells from accumulation of |
| 14929 | SIRT1 | sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae) | SIRT1 | 0.3 | cells from accumulation of oxidatively damaged proteins 50 and mammalian SIRT1 and SIRT3 might modulate mitochondrial activity 51 52 |
| 14931 | SIRT3 | sirtuin (silent mating type information regulation 2 homolog) 3 (S. cerevisiae) | SIRT3 | 0.3 | cells from accumulation of oxidatively damaged proteins 50 and mammalian SIRT1 and SIRT3 might modulate mitochondrial activity 51 52 |
| 14931 | SIRT3 | sirtuin (silent mating type information regulation 2 homolog) 3 (S. cerevisiae) | SIRT3 | 0.3 | accumulation of oxidatively damaged proteins 50 and mammalian SIRT1 and SIRT3 might modulate mitochondrial activity 51 52 |
| 14929 | SIRT1 | sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae) | SIRT1 | 0.3 | Recent studies have shown that overexpressing SIRT1 in mice seems to protect neurons from at least some |
| 10886 | SIRT2 | sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae) | SIR-2 | 1.3 | model of the neurodegenerative condition Huntington's disease upregulated expression of SIR-2 increased neuronal survival 54 |
| 10886 | SIRT2 | sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae) | SIR-2 | 1.3 | has also been recently proposed to increase the activity of SIR-2 (Ref Ref 55 |
| 10840 | SHC1 | SHC (Src homology 2 domain containing) transforming protein 1 | p66SHC | 3.2 | Another known mammalian-longevity gene product is p66SHC the p66 isoform of the adaptor protein SHC (Src-homology-2-containing) Src-homology-2-containing |
| 10840 | SHC1 | SHC (Src homology 2 domain containing) transforming protein 1 | p66 | 2.9 | Another known mammalian-longevity gene product is p66SHC the p66 isoform of the adaptor protein SHC (Src-homology-2-containing) Src-homology-2-containing |
| 10840 | SHC1 | SHC (Src homology 2 domain containing) transforming protein 1 | SHC | 4.2 | product is p66SHC the p66 isoform of the adaptor protein SHC (Src-homology-2-containing) Src-homology-2-containing |
| 11283 | SRC | v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) | Src-homology-2-containing | 0.2 | p66SHC the p66 isoform of the adaptor protein SHC (Src-homology-2-containing) Src-homology-2-containing |
| 10840 | SHC1 | SHC (Src homology 2 domain containing) transforming protein 1 | SHC | 4.2 | Normally SHC proteins serve as a molecular bridge linking various surface receptors |
| 10840 | SHC1 | SHC (Src homology 2 domain containing) transforming protein 1 | p66SHC | 3.2 | Mice lacking p66SHC have a 30% increased lifespan 57 |
| 10840 | SHC1 | SHC (Src homology 2 domain containing) transforming protein 1 | p66Shc | 3.2 | Interestingly when p66Shc - -mice were bred with mice that had a predisposition |
| 10840 | SHC1 | SHC (Src homology 2 domain containing) transforming protein 1 | p66Shc | 3.2 | vascular function that precede plaque formation were also absent in p66Shc - -animals 61 |
| 118 | ACO2 | aconitase 2, mitochondrial | aconitase | 2.1 | the activity of a set of metabolic enzymes such as aconitase and components of mitochondrial complex I that contain Fe-S clusters |
| 6881 | MAPK8 | mitogen-activated protein kinase 8 | JNKs | 0.3 | cytosolic stress pathways (for for example Jun N-terminal kinases (JNKs) JNKs and p38 |
| 6876 | MAPK14 | mitogen-activated protein kinase 14 | p38 | 0.3 | pathways (for for example Jun N-terminal kinases (JNKs) JNKs and p38 |
| 10840 | SHC1 | SHC (Src homology 2 domain containing) transforming protein 1 | p66SHC | 3.2 | out that drugs that augment sirtuins or those that inhibit p66SHC will only be effective in a discrete subset of age-related |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | Sod2 | 1.7 | Sod2 |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.6 | alpha-synuclein APP ATM JunD parkin peroxiredoxin I PINK1 Ras seladin-1 SIRT1 SIRT3 |
| 795 | ATM | ataxia telangiectasia mutated | ATM | 2.2 | alpha-synuclein APP ATM JunD parkin peroxiredoxin I PINK1 Ras seladin-1 SIRT1 SIRT3 SOD1 |
| 6206 | JUND | jun D proto-oncogene | JunD | 0.3 | alpha-synuclein APP ATM JunD parkin peroxiredoxin I PINK1 Ras seladin-1 SIRT1 SIRT3 SOD1 |
| 14581 | PINK1 | PTEN induced putative kinase 1 | PINK1 | 0.6 | alpha-synuclein APP ATM JunD parkin peroxiredoxin I PINK1 Ras seladin-1 SIRT1 SIRT3 SOD1 |
| 2859 | DHCR24 | 24-dehydrocholesterol reductase | seladin-1 | 1.3 | alpha-synuclein APP ATM JunD parkin peroxiredoxin I PINK1 Ras seladin-1 SIRT1 SIRT3 SOD1 |
| 14929 | SIRT1 | sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae) | SIRT1 | 0.3 | alpha-synuclein APP ATM JunD parkin peroxiredoxin I PINK1 Ras seladin-1 SIRT1 SIRT3 SOD1 |
| 14931 | SIRT3 | sirtuin (silent mating type information regulation 2 homolog) 3 (S. cerevisiae) | SIRT3 | 0.3 | APP ATM JunD parkin peroxiredoxin I PINK1 Ras seladin-1 SIRT1 SIRT3 SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.4 | ATM JunD parkin peroxiredoxin I PINK1 Ras seladin-1 SIRT1 SIRT3 SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | approximately 10% of cases are inherited and roughly a quarter of these inherited forms result from mutations in the cytosolic form of the antioxidant protein superoxide dismutase sod1 1 . |
| 12468 | UBC | ubiquitin C | ubiquitin c | 1.0 | at least five separate genes that are associated with parkinson's disease have been identified including those encoding alpha synuclein parkin ubiquitin c terminal hydrolase 1 dj1 and pten induced kinase 1 pink1 refs 2 4 . |
| 11138 | SNCA | synuclein, alpha (non A4 component of amyloid precursor) | alpha synuclein | 1.0 | at least five separate genes that are associated with parkinson's disease have been identified including those encoding alpha synuclein parkin ubiquitin c terminal hydrolase 1 dj1 and pten induced kinase 1 pink1 refs 2 4 . |
| 11138 | SNCA | synuclein, alpha (non A4 component of amyloid precursor) | alpha synuclein | 1.0 | for instance in the brains of patients with parkinson's disease alpha synuclein is modified by oxidative and nitrative stress 2 3 4 . |
| 11138 | SNCA | synuclein, alpha (non A4 component of amyloid precursor) | alpha synuclein | 1.0 | inhibiting mitochondrial function leads to increased alpha synuclein aggregation which can in turn lead to impaired mitochondrial function 5 6 . |
| 380 | AKR1A1 | aldo-keto reductase family 1, member A1 (aldehyde reductase) | alcohol dehydrogenase | 1.0 | hypotheses exist regarding how a beta induces injury but one possibility is that this peptide can directly induce oxidative stress 12 potentially through an interaction with the mitochondrial protein alcohol dehydrogenase 13 . |
| 18985 | DCXR | dicarbonyl/L-xylulose reductase | carbonyl reductase | 1.0 | the levels of carbonylated proteins increase dramatically with age 15 and mutants of d. melanogaster that lack carbonyl reductase activity suffer from neurodegenerative symptoms 16 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | a number of groups have proposed that a plasma membrane superoxide generating enzyme system known as the nadph oxidase is involved 22 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | subsequent analysis showed that components of the nadph oxidase system are expressed in other cell types and that a large family of tissue specific oxidases exist 23 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | consistent with its potential role in vascular disease knockout mice that are deficient in nadph oxidase have reduced vascular oxidant production and in some settings reduced atherosclerosis 24 25 . |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | superoxide dismutase 2 | 1.0 | superoxide dismutase 2 +/ sod2 +/ mice which lack one copy of this mitochondrial antioxidant protein show an increased rate of atherosclerotic plaque formation 26 . |
| 795 | ATM | ataxia telangiectasia mutated | ataxia telangiectasia mutated | 1.0 | for example there is evidence that p53 myc ataxia telangiectasia mutated atm and ras can all alter intracellular ros levels 31 . |
| 2859 | DHCR24 | 24-dehydrocholesterol reductase | seladin 1 | 1.0 | another group noted that inhibiting seladin 1 could also block ras or oxidant induced senescence 42 seladin 1 had been previously discovered in the context of alzheimer's disease in which it seems to be selectively downregulated 43 . |
| 2859 | DHCR24 | 24-dehydrocholesterol reductase | seladin 1 | 1.0 | notably following hydrogen peroxide treatment seladin 1 translocates to the nucleus where it seems to bind to and stabilize p53. |
| 11138 | SNCA | synuclein, alpha (non A4 component of amyloid precursor) | alpha synuclein | 1.0 | alpha synuclein app atm jund parkin peroxiredoxin i pink1 ras seladin 1 sirt1 sirt3 sod1 |
| 2859 | DHCR24 | 24-dehydrocholesterol reductase | seladin 1 | 1.0 | alpha synuclein app atm jund parkin peroxiredoxin i pink1 ras seladin 1 sirt1 sirt3 sod1 |