S6k | RPS6-p70-protein kinase | Ubiquitous overexpression of a dominant-negative form of S6k (alias dS6K) increases mean lifespan by 22% and overexpression of a constitutively active form of S6k decreases mean lifespan by 34% at 29°C. Overexpression of a dominant-negative form of S6k protects mutants from deleterious effects of rich food, as if mimicking the effect of DR [15186745]. | Fruit fly |
GH1 | Growth hormone 1 | Transgenic mice overexpressing bovine GH1 are bigger than controls and display early onset of pathological changes in the kidneys such glomerulosis and glomerulonephritis as well as signs of premature aging such as a shortened lifespan, increased astrogliosis, shortened reproductive lifepsan and early onset of age-related changes in cognitive function, hypothalamic neurotransmitter turnover, and plasma corticosterone levels [14583653]. | Cattle |
let-60 | LEThal | The let-60(n1046gf) activating mutation greatly reduces lifespan of wild-type, weakly suppresses constitutive dauer diapause in daf-2 and age-1 mutants and extends lifespan induced by mutation of daf-2 [16164423]. | Nematode |
tdp-1 | TAR DNA-binding Protein homolog 1 | tdp-1(ok803) mutation increases mean and maximum lifespan at 20 degree Celsius but not at 25 degree Celsius. tdp-1(ok803) reduce the lifespan of daf-2(e1370) mutants, but does not does not reduces the lifespan of daf-16(mu86) mutants. RNAi against tdp-1 reduces lifepsna of daf-2(e1370) mutants. tdp-1 overexpression strains have a reduced lifespan at 20 and 25 degree Celsius [Vaccaro et al. 2012]. | Nematode |
CLN3 | CycLiN 3 | Overexpression shortens chronological lifespan together with age-dependent increases in genome instability and apoptosis. While around 80% of wild-type cells are alive almost non CLN3 overexpressers are alive (under condition that avoids adaptive regrowth) [17710147]. | Budding yeast |
Terf2 | telomeric repeat binding factor 2 | Overexpression results in signs of premature ageing. | House mouse |
YDC1 | Yeast DihydroCeramidase 1 | Overexpression of YDC1 decreases chronological lifespan by 40% [19059240] | Budding yeast |
LBR | Lamin B receptor | Overexpression of Lamin B receptor in the adult muscle and in the abdominal fat body results in a 54% and 46% reduction of mean lifespan, respectively [18494863]. | Fruit fly |
kuk | kugelkern | Overexpression of kugelkern in the adult muscle results in a 60% reduction of mean lifespan [18494863]. | Fruit fly |
Gh | Growth hormone | Overexpression of GH is associated wtih markedly reduced lifespan and various indices of premature aging [8100276]. Transgenic mice overexpressing bovine GH1 are bigger than controls and display signs of premature aging such as a shortened lifespan, glomerulosclerosis and glomerulonephritis, increased astrogliosis, and early onset of age-related changes in cognitive function [14583653]. | House mouse |
DNApol-gamma35 | DNA polymerase gamma 35kD | Overexpression of DNApol-gamma35 (DNA polymerase gamma) in the nervous system results in a decrease in the median lifespan ranging from 39% to 52% [17999718].
| Fruit fly |
nlp-7 | Neuropeptide-Like Protein | nlp-7 RNAi or overexpression reduces oxidative stress resistance and shortens lifespan of wild-type under AL. nlp-7 RNAi significantly reduces extended lifespan of eat-2 mutants, but failed to block lifespan extension of age-1 or clk-1 mutants. Lifespan of nlp-7 mutants increases only moderately by sDR [19783783]. nlp-7 expression is induced under DR via the use of a chemically defined axenic medium [17023606] and by sDR [19783783]. | Nematode |
mir-239 | — | Mutating mir-239 increases mean and maximum lifespan by 12 and 36%, respectively, whereas overexpressing mir-239 decreases mean and maximum lifespan by 13 and 17 - 33%, respectively [21129974]. | Nematode |
sdhC | succinate dehydrogenase, cytochrome b556 subunit | Mutants expressing a dominant negative form of sdhC in the nervous system have a 22% reduced mean lifespan and signs of oxidative stress induction [17854771]. | Fruit fly |
Trp53 | Transformation related protein 53 | Mice heterozyogous for an allele of p53 that removes the 5' portion of the protein demonstrate decreased cancer, permature aging phenotypes, and shortened lifespan in the mixed inbred C57BL/6â129/Sv background. It has been proposed that the this allele of p53 results in increased activity/overexpression [11780111]. Decreased activity of Trp53 results in increased cancer and decreased apoptosis. Mutant mice with activated Trp53 display enhanced resistance to spontaneous tumours and signs of premature ageing including reduced lifespan, osteoporosis, organ atrophy and a diminished stress tolerance [11780111]. However, super-p53 mice generate by a transgenic copy of a large genomic segment containing an intact and complete copy of p53 have an ehanced response to DNA damage, are significantly protected from cancer and had no indication of accelerated aging [12426394]. super-Ink4a/Arf/p53 mice have a synergic protection against cancer and delayed aging [Workshop RoSyBa 2011]. | House mouse |
OSH3 | OxySterol binding protein Homolog 3 | Mean replicative lifespan of OSH3 deletion mutant is not significant different from wild type. Overexpression of OSH3 with the promoter of VAC8 shortens mean replicative lifespan ad promotes vacuolar fusion [Xia et al. unpublished]. | Budding yeast |
SCP1 | S. cerevisiae CalPonin 1 | Increasing actin dynamics by deletion of SCP1, encoding an actin bundling protein, increases replicative lifespan by 67% as well as chronological lifespan by 88%, whereas its overexpression leads to elevuated ROS levels and reduces chronological lifespan (in KAY446 strain) [15024029]. SCP1 is related to mammalian SM22/transgelin which is induced during senescence [9570922]. | Budding yeast |
Gr63a | Gustatory receptor 63a | Gr63a loss-of-function in female flies leads to 30% extended mean lifespan, increased fat deposition, and enhanced resistance to some (but not all) environmental stresses. Lifespan of males is not extended [20422037].
Overexpression of Gr63a has modest negative effect on lifespan [20422037]. | Fruit fly |
gpa2 | Guanine nucleotide-binding protein alpha-2 subunit | gpa2 (alias git8) encodes the alpha subunit of a heterotrimeric G protein, which acts downstream of Git3. Git8 activity accelerates aging and inhibits the lifespan-extending effect of DR. Constitutive active mutation of gpa2 decreases chronological lifespan under AL (2% glucose) and almost completely cancels out the lifespan extending effect of DR (0.2% glucose) [19266076]. | Fission yeast |
SNF1 | Sucrose NonFermenting 1 | Forced overexpression (high-copy 2 micro expression) of SNF1 shortens replicative lifespan to 75% of wild-type and is accompanied by signs of premature ageing, including progressive sterility, enlargement and fragmentation of the nucleus, redistribution of Sir3 to the nucleus, and more rapid accumulation of extrachromosomal rDNA circles [10921902]. SNF1 overexpression also reduced chronological lifespan [19164565]. Deletion of SNF1 increases replicative lifespan by 50% in the alpha strain [19030232], but decreases chronological lifespan [21076178]. | Budding yeast |
MAPT | microtubule-associated protein tau | Expression of wild-type human MAPT (tau) moderately shortened lifespan. Expression of a mutant form of human MAPT (Arg406 Trp), associated with an early onset familial form of demetia, results in a several shortened lifespan. MAPT is implicated in the pathogenesis of Alzeimer's disease and related disorders in humans. Transgenic flies exhibit key features of the human disorders: adult onset, progressive neurodegeneration, early death, enhanced toxicity of mutant tau, accumulation of abnormal tau, and relative anatomic selectivity. However, neurodegeneration occurred without the neurofibrillary formation that is observed in humans disease and some rodent taupathy models [11408621]. | Human |
GTS1 | Glycine Threonine Serine repeat protein 1 | Deletion or overexpression of GTS1 shortens replicative lifespan significantly and slightly, respectively (wt:26, Delta:16 and OE:24) [8573138]. | Budding yeast |
AFG3 | ATPase Family Gene 3 | Deletion of the mitochondrial AAA protease AFG3 increases replicative lifespan by 20% in the alpha and a strains [18340043], but decreases chronological lifespan by 37 - 51% in diploid cells [21447998].
AFG3 deletion changes mean, median and maximum lifespan by 15 to 26% 17 to 30% and -25 to +58%, respectively.
AFG3 deletion leads to reduced cytoplasmic mRNA translation and its lifespan extension is independent of Sir2 and Hac1, but requires Gcn4. AFG3 deletion further extends the lifespan of cell deficient in both SIR2 and FOB1, but fails to extend the lifespan of dietary restricted cells or cells lacking GCN4. Gcn4 protein levels are increased in afg3 mutants. The deletion of AFG3 fails to extend the replicative lifespan in the W303AR strain. AFG3 deletion does deletion extend the replicative lifespan at 15°C. | Budding yeast |
RPL6A | Ribosomal Protein of the Large subunit 6A | Deletion of RPL6A decrease mean replicative lifespan by 25% in the alpha strain [18340043; 18423200], but increases mean replicative lifespan by 40% in the remade strain. Its deletion non-significantly increases mean replicative lifespan in the ORF collection [22377630]. | Budding yeast |
HES1 | Homologous to kES1 1 | Deletion of HES1 (alias OSH5) extends replicative lifespan and is non-additive with moderate DR. Elevation of OSH5 levels by an ERG6 promoter reduces mean, median and maximum replicative lifespan by 25, 18 and 29%. HES1 is required for the longevity effect of DR, Perg6-OSH6, Perg6-ERG2 and Perg6-OSH7 (genetic mimetics of DR). Hes1 is upregulated in response to sterol down-regulation including DR. Deletion of OSH5 delays different steps of endocytosis, a sterol-requireing process [Xia et al., unpublished].
Perg6-OSH6 osh5 double mutant have a lifespan significantly shorter than that of Perg6-OSH6 [Xia et al. upublished]. | Budding yeast |