| BLM | Bloom syndrome, RecQ helicase-like | BLM mutation cuases Bloom syndrom. Individuals with Bloom syndrome have a shortend life expectancy []. Death is primary due to cancer, particulary leukemia and lymphoma [German, 1992]. Bloom syndrome is not a premature aging disease. Bloom syndrome characteristics are grwoth deficiency, sun-snesitivity, telangiectatic hypo- and hyperpigmented skin, predisposition to malignancy, and chromosomal instability [5770175]. | Human |
| CG3776 | — | Both overexpression and underexpression of CG3776 (alias Jhebp29) reduces the mean lifespan, where the reduction in males is slightly higher.
The lifespan of male flies with under- and overexpressed CG3776 is reduced by 38.8 and 42.6%, respectively when compared with Oregon R flies.The lifespan of female flies with under- and overexpressed CG3776 is reduced by 31.6 and 35%, respectively when compared to Oregon R flies.
Among the males and females, relatively to Oregon R and EP835/CyO, the age-specific survival of EP835/EP835 and EP835/Gal4 is reduced in both log-rank and Wilcoxon tests (P < 0.001); survival of EP835/EP835 and EP835/Gal4 differed using the log-rank-test (male: P<0.001; female: P=0.027) [18275960].
| Fruit fly |
| bra-1 | BMP receptor Associated protein family | bra-1(nk1) mutation reduces mean lifespan by 6-25% [17900898]. | Nematode |
| Bub1b | budding uninhibited by benzimidazoles 1 homolog, beta (S. cerevisiae) | Bub1b hypomorphic mutation decreases median lifespan by 60% (from 15 to 6 months) and such mutant mice that procude low levels of the protein are prone to aneuplody and develop many phenotypes suggestive of accelerated aging, including short lifespan, growth retardation, sarcopenia, lordokyphosis, progressive bilateral cataracts, substantial loss of sub dermal adipose tissue, spinal kyphosis, muscle atrophy, reduced dermal thickness and decreased wound healing [15208629; 17272762; 16781018; 18516091].
Moreover, there is a pronounced increase in senescent associated Beta-galactosidase expression in late generation Bub1b mutant mice, indicative of increased rate of cellular senescence. Homozyogous knockout of Bub1b results in lethality, while heterozygous animals exhibit no aging phenotypes [15208629].
Sustained high-level expression of BubR1 preserves genomic integrity and reduces tumorgenesis (even in the presence of genetic alterations that strongly promote aneuplodization and cancer, such as oncogenic Ras) and extends the lifespan and delays age-related deterioriation and aneuploidy in several tissues [23242215].
BubR1 overabundance exerts its protective effect by correcting mitotic checkpoints defects [23242215].
BubR1 expression level declines with age in various tissues [15208629; 17272762; 16781018].
The median and maximum lifespan of mice with a nonsense mutation 2211insGTTA in BubR1 is significantly reduced. BubR1(+/GTTA) mice develop several aging-related phenotypes at an accelerated rate, including catarct formation, lordokyphosis, skeletal muscle wasting, impaired exercise ability, and fat loss. Further BubR1(+/GTTA) mice develop mild anaplodies and exhibit enhanced growth of carcinogen-induced tumors [Wijshake et al. 2012].
| House mouse |
| Igf1 | Insulin-like growth factor 1 (somatomedin C) | Cardiac specific overexpression of Igf1 results in a 23% increase in median lifespan, though no increase in maximum lifespan [17973971]. | House mouse |
| Cdk5 | Cyclin-dependent kinase 5 | Cdk5 loss-of-function mutations result in defective axon guidance, age-dependent behavioral deficits and reduced lifespan by about one third [17368005]. | Fruit fly |
| PNC1 | Pyrazinamidase/NiCotinamidase 1 | Cells with 5 copies of PNC1 have a 70% longer replicative lifespan which is cancelled out by SIR2 deletion. PNC1 is upregulated under glucose DR [12736687]. Pnc1 reduces cellular nicotinamide levels, a product and noncompetitive inhibitor of Sir2 deacetylation reaction. Overexpression of PNC1 suppresses the effect of exogenously added nicotinamide on Sir2-dependent silencing at HM loci, telomeres and rDNA loci [12736687; 14729974]. Pnc1 catalyses the breakdown of nicotinamide to nicotinate and ammonia [12736687]. Deletion of PNC1 shortens replicative lifespan approximately by 10% [12736687] and largely prevents replicative lifespan extension of 0.5% glucose restriction. 0.5% glucose restriction slightly extends median replicative lifespan (by 10 - 15%) but not maximum replicative lifespan in pnc1Delta [14724176]. PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, lifespan, and Hst1-mediated transcriptional repression [14729974]. Increased expression of PNC1 is both necessary and sufficient for replicative lifespan extension by DR and low-intensity stress. Under non-stressing conditions (2% glucose, 30 degree Celsius), a strain with additional copies of PNC1 (5XPNC1) has 70% longer replicative lifespan than the wild-type and some cells live for more than 70 divisions. Neither DR nor heat stress further increase the lifespan of the 5XPNC1 strain [12736687]. PNC1 deletion decreases chronological lifespan [17110466]. | Budding yeast |
| cert | ceramide transfer protein | cert mutants exhibit a shortened lifespan accompanied by enhanced oxidative damage to cellular proteins and metabolic compromise, such as increasing glucose levels, reminiscent of premature aging [17592126]. | Fruit fly |
| CHL1 | CHromosome Loss 1 | CHL1 deletion mutant exhibits a shortened mean and maximum lifespan by 36 and 29%, respectively, as well as hypersensitivity to heat stress. CHL1 may modulate transcriptional silencing in the presence of Sir proteins [16182251]. | Budding yeast |
| Cisd2 | CDGSH iron sulfur domain 2 | Cisd2 knockouts expire premature ageing and reduced lifespan [19451219]. A persistent level of Cisd2 achieved by transgenic expression extends mean, median and maximum lifespan without any apparent deleterious side effects [22661501]. | House mouse |
| Mcm2 | minichromosome maintenance deficient 2 mitotin (S. cerevisiae) | Conditional knockouts with reduced expression develop normally but lifespan is greatly reduced with most animals living 10-12 weeks accompanied by deficiencies in the proliferative cell compartments of several tissues and increased cancer incidence. | House mouse |
| wis1 | — | Constitutive active mutation of wis1 extends chronological lifespan and there is no further beneficial effect of DR [20075862]. | Fission yeast |
| mir-277 | — | Constitutive miR-277 expression shortens lifespan and synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype. Transgenic inhibition with a miRNA sponge construct also shortens lifespan [23669073].
miR-277 is downregulated during adult life [23669073].
mir-277 controls branched-chain amino acid catabolism and as a result it can modulate the activity of TOR kinase [23669073]. | Fruit fly |
| ctl-1 | CaTaLase 1 | ctl-1 loss of function shortens lifespan to 77% of wild-type animals. ctl-1 mutants accumulate fluorescent material faster than wild-type, indicating accelerated aging [12610632]. ctl-1 mutation prevents lifespan extension by daf-2 or clk-1. Mutation of ctl-1 reudces catalase activty by 50% [10335847].
All these results have been retracted. | Nematode |
| cup-4 | Coelomocyte UPtake defective 4 | cup-4 RNAi or overexpession reduces oxidative stress resistance and shortens lifespan of wild-type under AL. cup-4 RNAi significantly reduces the extended lifespan of eat-2 mutants, but failed to block lifespan extension of age-1 or clk-1 mutants. Lifespan of cup-4 mutants increases only moderately by sDR [19783783]. | Nematode |
| daf-18 | Abnormal DAuer Formation | daf-18 is required for complete dauer formation. Overexpression increases adult lifespan in individual tissues [16153634]. daf-18 mutation partially suppresses the lifespan extension of age-1 and daf-2 mutants. daf-18 mutants are defective for dauer formation and form some dauer-like larvae when starved [7789761; 8601482]. | Nematode |
| daf-3 | abnormal DAuer Formation | daf-3(mgDf90) mutation decreases mean lifespan by 0-16% and maximum lifespan by up to 9-21%. daf-3(mgDf90) decreases mean lifespan even by 19% [17900898]. Mutation of daf-3 results in a wild-type lifespan, but greatly extends the lifespan of the long-lived daf-9 mutant [11782415]. daf-3 mutations are dauer defective. | Nematode |
| daf-5 | abnormal DAuer Formation | daf-5(e1386) mutation reduces mean lifespan by 19% and maximum lifespan by 21% [17900898]. | Nematode |
| DAP2 | Dipeptidyl AminoPeptidase 2 | DAP2 deletion decreases mean and maximum replicative lifespan under AL by 19 and 36%, respectively, and cancels out the lifespan extending effect of moderate DR [22912585]. | Budding yeast |
| dcp-66 | Deacetylase Complex Protein 66 | dcp-66 RNAi shortens the mean lifespan by 29% and suppresses lifespan extension by isp-1 mutation, but does not significantly affect lifespan extension neither by eat-2 nor daf-2 mutation [22829775]. | Nematode |
| dct-11 | DAF-16/FOXO Controlled, germline Tumor affecting 11 | dct-11 stimulates the growth of gld-1 tumors. RNA interference of dct-11 increases mean lifespan up to 19% in a gld-1 mutant background and reduces mean lifespan by 10% in a wild-type background [17934462]. | Nematode |
| dct-18 | DAF-16/FOXO Controlled, germline Tumor affecting 18 | dct-18 stimulates the growth of gld-1 tumors. RNA interference of dc-18 increases mean lifespan up to 12% in a gld-1 mutant background and reduces mean lifespan by 8% in wild-type worms [17934462]. | Nematode |
| Sirt2 | — | Decreased expression of Sirt2 by RNA interference causes lethality during development. Silencing in neurons shortened mean lifespan by 20% [17159295]. | Fruit fly |
| Sirt6 | — | Decreased expression of Sirt6 by RNA interference causes lethality during development. Sirt6 silencing in neurons shortens mean lifespan by 20% [17159295]. | Fruit fly |
| YKU70 | Subunit of the telomeric Ku complex (Yku70p-Yku80p) | Deletion fo YKU70 shortens lifespan, but does not accelerate the normal aging process [10521401]. YKU70 null mutants are defective for non-homologous end-joining [8754818] and for telomeric silencing [9635192]. | Budding yeast |
