Functional Clustering of Genes Influencing Ageing

Important notice: The addition to GenAge of a list of ageing- and longevity-associated genes in model organisms has rendered the below functional clustering obsolete. Therefore, the list below is considered deprecated, will not be updated again, and may be deleted sometime in the future. Users are encouraged to consult GenAge's section on model organisms.

Gene name Alternative name/phenotype Function Organism Main reference
Calcium metabolism
klotho unknown but it appears to be involved in calcium metabolism M. musculus Kuro-o et al., 1997
klotho unknown but it appears to be involved in calcium metabolism H. sapiens Arking et al., 2002
SMP30 Senescence marker protein-30 suppresses cell proliferation and regulates calcium homeostasis M. musculus Ishigami et al., 2002
Energy restriction and the GH/IGF-1 axis
age-1 phosphatidylinositol 3-OH kinase insulin signal transduction C. elegans Morris et al., 1996
akt-1 AKT1 insulin/insulin-like signal transduction C. elegans Paradis and Ruvkun, 1998
atp-3 Mitochondrial ATP synthase, O subunit subunit of mitochondrial ATP synthase C. elegans Dillin et al., 2002
C/EBP alpha CCAAT/enhancer-binding protein, alpha fat metabolism M. musculus Chiu et al., 2004
C/EBP beta CCAAT/enhancer-binding protein, beta fat metabolism M. musculus Chiu et al., 2004
Ceinsulin-1 ins-18 homologue of mammalian insulin/insulin-like growth factor C. elegans Kawano et al., 2000
chico insulin receptor substrate D. melanogaster Clancy et al., 2001
daf-2 insulin receptor-like gene insulin signalling C. elegans Kimura et al., 1997
daf-16 forkhead transcription factor transcriptional regulation in metabolic and developmental pathways C. elegans Ogg et al., 1997
eat-2 nicotinic acetylcholine receptor subunit C. elegans Lakowski et al., 1998
egl-4 cGMP-dependent protein kinase unknown but it appears to regulate cell size maybe through the insulin pathway C. elegans Hirose et al., 2003
F26E4.6 component of the mitochondrial Complex IV C. elegans Lee et al., 2003
FIRKO fat-specific insulin receptor knockout insulin pathway M. musculus Bluher et al., 2003
GH growth hormone tissue proliferation M. musculus Bartke, 2003
GH-1 Laron syndrome tissue proliferation H. sapiens Besson et al., 2003
GHR/BP Growth hormone receptor GH transmembrane receptor M. musculus Cochigano et al., 2000
Ghrhr Growth hormone-releasing hormone receptor regulation of GH synthesis and secretion in the pituitary M. musculus Flurkey et al., 2001
IGF-R1 IGF-I receptor proliferation and growth M. musculus Holzenberger et al., 2003
IGF-R1 IGF-I receptor proliferation and growth H. sapiens Roback et al., 1991
Indy unknown D. melanogaster Rogina et al., 2000
InR insulin-like receptor insulin pathway D. melanogaster Tatar et al., 2001
klotho unknown but it may inhibit INS/IGF1 signalling M. musculus Kuro-o et al., 1997
klotho unknown but it may inhibit INS/IGF1 signalling H. sapiens Arking et al., 2002
Methuselah CD97 unknown but a member of the 7-TM protein superfamily D. melanogaster Lin et al., 1998
PDK1 PDPK1 signal transduction involving insulin, PI3K, and AKT C. elegans Paradis et al., 1999
Pit1 Snell dwarf mouse pituitary-specific transcription factor M. musculus Flurkey et al., 2001
Pit1 combined pituitary hormone deficiency pituitary-specific transcription factor H. sapiens Radovick et al., 1992
Prop1 Ames dwarf mouse pituitary transcriptional activation M. musculus Brown-Borg et al., 1996
Prop1 "Little People" of Krk pituitary transcriptional activation H. sapiens Krzisnik et al., 1999
sir2 Silent Information Regulator 2 NAD(+)-dependent deacetylase S. cerevisiae Kaeberlein et al., 1999
sir-2.1 sirtuin 2 NAD(+)-dependent deacetylase C. elegans Tissenbaum and Guarente, 2001
Sir2 Silent Information Regulator 2 NAD(+)-dependent deacetylase D. melanogaster Rogina & Helfand, 2004
Sirt1 Sirtuin 1 NAD(+)-dependent deacetylase M. musculus Moynihan et al., 2005
Stunted sun unclear but may be a mitochondrial ATP synthase D. melanogaster Cvejic et al., 2004
TOR target of rapamycin family translation initiation and growth D. melanogaster Kapahi et al., 2004
uPA urokinase-type plasminogen activator appetite suppressor M. musculus Miskin and Masos, 1997
DNA metabolism
Atm DNA damage recognition M. musculus Wong et al., 2003
ATM ataxia telangiectasia mutated DNA damage recognition H. sapiens Gatti et al., 1991
beta-pol DNA polymerase beta DNA replication and repair M. musculus Cabelof et al., 2006
BLM helicase M. musculus Chester et al., 1998
BLM Bloom syndrome helicase H. sapiens German, 1969
Brca1 DNA repair M. musculus Cao et al., 2003
BRCA1 breast-ovarian cancer DNA repair H. sapiens Castilla et al., 1994
Bub3 mitotic checkpoint M. musculus Baker et al., 2006
BubR1 mitotic checkpoint M. musculus Baker et al., 2004
CDC25 GRF2 GDP-GTP exchange factor S. cerevisiae Lin et al., 2000
CSA Cockayne syndrome or CKN1 DNA repair H. sapiens Henning et al., 1995
DNA-PK severe combined immune-deficient mice DNA repair M. musculus Araki et al., 1997
dSir2 Sir2 epigenetic gene silencing D. melanogaster Newman et al., 2002
Ercc1 DNA repair M. musculus Weeda et al., 1997
HRP-1 telomere-binding protein C. elegans Rogina et al., 2002
Ku70 Thyroid-Lupus autoantigen homologous recombination and nonhomologous end joining H. sapiens Reeves and Sthoeger, 1989
Ku70 G22P1 homologous recombination and nonhomologous end joining M. musculus Li et al., 1998
Ku86 XRCC5 homologous recombination and nonhomologous end joining M. musculus Vogel et al., 1999
Lmna Lamin A unclear but may be involved in DNA metabolism M. musculus Mounkes et al., 2003
LMNA Hutchinson-Gilford syndrome unclear but may be involved in DNA metabolism H. sapiens Eriksson et al., 2003
MTH1 8-oxo-dGTPase repair of oxidative-damage to DNA M. musculus Tsuzuki et al., 2001
Nibrin Nijmegen breakage syndrome DNA double-strand repair H. sapiens Varon et al., 1998
OGG1 8-oxoguanine DNA glycosylase repair of oxidative-damage to DNA M. musculus Klungland et al., 1999
p53 tumour suppressor M. musculus Tyner et al., 2002
p53 Li-Fraumeni syndrome tumour suppressor H. sapiens Varley, 2003
p63 tumour suppressor M. musculus Keyes et al., 2005
p63 ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome 3 tumour suppressor H. sapiens Celli et al., 2005
PARP Poly(ADP-Ribose) polymerase chromatin-associated enzyme involved in DNA repair M. musculus d'Adda di Fagagna et al., 1999
PARP Poly(ADP-Ribose) polymerase chromatin-associated enzyme involved in DNA repair Mammals Grube and Burkle, 1992
PASG proliferation associated SNF2-like gene DNA methylation M. musculus Sun et al., 2004
PMS2 DNA mismatch repair M. musculus Narayanan et al., 1997
PolgA mitochondrial DNA polymerase DNA replication and repair M. musculus Trifunovic et al., 2004
RAD27 exonuclease S. cerevisiae Hoopes et al., 2002
RAD51 homologous recombination S. cerevisiae Park et al., 1999
RAD52 homologous recombination S. cerevisiae Park et al., 1999
Rae1 mitotic checkpoint M. musculus Baker et al., 2006
Rpd3 RPD3L1 histone deacetylase D. melanogaster Rogina et al., 2002
sir2 Silent Information Regulator 2 NAD(+)-dependent deacetylase S. cerevisiae Kaeberlein et al., 1999
sir-2.1 sirtuin 2 NAD(+)-dependent deacetylase C. elegans Tissenbaum and Guarente, 2001
Sir2 Silent Information Regulator 2 NAD(+)-dependent deacetylase D. melanogaster Rogina & Helfand, 2004
SIRT1 Sirtuin 1 epigenetic gene silencing M. musculus McBurney et al., 2003
SIRT6 Sirtuin 6 DNA repair M. musculus Mostoslavsky et al., 2006
Terc RNA component of telomerase elongating the telomeres S. cerevisiae Lunblad and Szostak, 1989
Terc RNA component of telomerase elongating the telomeres M. musculus Wong et al., 2003
Terc RNA component of telomerase elongating the telomeres M. musculus Chang et al., 2004
Terc Dyskeratosis congenita elongating the telomeres H. sapiens Vulliamy et al., 2001
top3b DNA topoisomerase IIIbeta chromosomal structure M. musculus Kwan and Wang, 2001
WRN Werner syndrome helicase + exonuclease H. sapiens Yu et al., 1996
WRN Werner syndrome helicase + exonuclease M. musculus Chang et al., 2004
XPD DNA repair M. musculus de Boer et al., 2002
XPD Xeroderma pigmentosum, group D DNA repair H. sapiens Stefanini et al., 1986
ZMPSTE24 zinc metallopeptidase (STE24 homolog) post-translational processing of LMNA M. musculus Varela et al., 2005
Oxidant levels and redox potential
CAT catalase anti-oxidant enzyme C. elegans Melov et al., 2000
CAT catalase anti-oxidant enzyme D. melanogaster Orr and Sohal, 1994
CAT catalase anti-oxidant enzyme M. musculus Schriner et al., 2000
CAT catalase anti-oxidant enzyme M. musculus Schriner et al., 2005
CAT hereditary catalase deficiencies anti-oxidant enzyme H. sapiens Goth and Eaton, 2000
clk-1 COQ7 mitochondrial inner membrane protein involved in ubiquinone biosynthesis C. elegans Ewbank et al., 1997
clk-1 mclk-1 mitochondrial inner membrane protein involved in ubiquinone biosynthesis M. musculus Liu et al., 2005
COX1 subunit I of the cytochrome c oxidase complex mitochondrial metabolism P. anserina Begel et al., 1999
COX5 subunit V of the cytochrome c oxidase complex mitochondrial metabolism P. anserina Dufour et al., 2000
GPX glutathione peroxidase anti-oxidant enzyme M. musculus Ho et al., 1997
GSR glutathione reductase anti-oxidant enzyme D. melanogaster Mockett et al., 1999
MSRA methionine sulfoxide reductase A oxidative-damage repair D. melanogaster Ruan et al., 2002
MSRA methionine sulfoxide reductase A oxidative-damage repair M. musculus Moskovitz et al., 2001
MTH1 8-oxo-dGTPase repair of oxidative-damage to DNA M. musculus Tsuzuki et al., 2001
OGG1 8-oxoguanine DNA glycosylase repair of oxidative-damage to DNA M. musculus Klungland et al., 1999
p66shc apoptosis and redox potential M. musculus Migliaccio et al., 1999
Prdx1 peroxiredoxin anti-oxidant M. musculus Neumann et al., 2003
SOD super oxide dismutase anti-oxidant enzyme C. elegans Melov et al., 2000
SOD1 cytoplasmic super oxide dismutase anti-oxidant enzyme D. melanogaster Parkes et al., 1998
SOD1 cytoplasmic super oxide dismutase anti-oxidant enzyme Lasius niger Parker et al., 2004
SOD1 cytoplasmic super oxide dismutase anti-oxidant enzyme M. musculus Huang et al., 2000
SOD2 mitochondrial super oxide dismutase anti-oxidant enzyme M. musculus Van Remmen et al., 2003
Thdx1 thioredoxin redox-active protein M. musculus Mitsui et al., 2002
Stress response
hep hemipterous activates JNK D. melanogaster Wang et al., 2003
hsf-1 heat-shock factor 1 transcription factor that regulates response to stress C. elegans Garigan et al., 2002
Hsp70 heat-shock protein D. melanogaster Tatar et al., 1997
Hsp70F Hsp-6 possible heat shock protein C. elegans Yokoyama et al., 2002
JNK Jun N-terminal protein kinase stress-activated protein kinase D. melanogaster Wang et al., 2003
Methuselah CD97 unknown but a member of the 7-TM protein superfamily D. melanogaster Lin et al., 1998
PCMT protein carboxyl methyltransferase repair of abnormal protein aspartyl residues D. melanogaster Chavous et al., 2001
puc puckered JNK-specific phosphatase D. melanogaster Wang et al., 2003
rad-8 tyrosine kinase receptor C. elegans Murakimi and Johnson, 1998
rad-8 unknown but may be involved in stress response D. melanogaster Ishii et al., 1994

Please note: some relevant references are missing as only one reference per gene was selected. Although mammalian models were preferred, major findings in lower organisms are also featured. Also note that some overlap may exist between the groups, particularly between proteins involved in stress response and oxidative stress.