| SWI4 | SWItching deficient 4 | Deletion of SWI4 shortens replicative lifespan by approximately 90% [11805047]. SSD1-V partially suppresses the short lifespan of a swi4 mutant.
Mutation of swi4 results in slow growth and temperature sensitivity, both of which are suppressed by SSD1-V [11805047]. | Budding yeast |
| SUN4 | — | Disruption of SUN4 shortens mean (87.5% of normal), but not maximum, replicative lifespan in BKY1-14c [Austriaco, N.R. (1996) âUTH1 and the Genetic Control of Aging in the Yeast, Saccharomyces cerevisiae.â Ph.D. Thesis, Massachusetts Institute of Technology; 8810036]
SUN4 mutation causes failure of daughter cells to completely detach and results in a multi-budded morphology [10683261]. | Budding yeast |
| SIM1 | Start Independent of Mitosis 1 | Disruption of SIM1 shortens mean (87.5%), but not maximum, lifespan without causing any other gross changes in cell cycle parameter or growth characteristics [8810036].
Cells bearing deletions in CLB1-4 are unable to undergo mitosis and normally arrest in G2. SIM1 disruption in clb1-4 mutant backgrounds will allow a second round of DNA synthesis without mitosis [8574583]. sim1delta;uth1delta double mutants exhibit various defects, including binucleated cells, benomyl sensitivity, heat shock sensitivity, inability to store glycogen, sensitivity to starvation and failure of spores to germinate [10612745]. | Budding yeast |
| RSR1 | RaS-Related 1 | Deletion of RSR1 (alias BUD1) shortens replicative lifespan [9789734]. | Budding yeast |
| Rgn | regucalcin | Survival among make animals lacking Rgn (alias SMP30) is 50% at 180 days compared to 100% among controls [N. Maruyama, unpublished data].
SMP30-/- mutant mice are indstuguishibale form their SMP30+/+ littermates in terms of development and fertilization capacity [12368201]. However, -/- mice were more susceptible to liver injury after treatment with anti-FAS antibody. SMP30-/- hepatocytes cultures in vitro are more susceptible to apoptosis induced by tumor-necrosis factor (TNF-alpha) plus actinomycin D (ActD) than SMP30+/+ hepatocytes.
| House mouse |
| BNA6 | Biosynthesis of Nicotinic Acid 6 | Deletion of BNA6 (alias QPT1) has no effect on replicative lifespan and is not required for lifespan extension by DR, but is lethal with mutation of NPT1 [11000115]. Deletion of BNA6 decreases chronological lifespan [17110466]. | Nematode |
| POL1 | POLymerase 1 | Mutation of POL1 results in a 20-60% reduction in mean lifespan (in SS111) [12024027] | Budding yeast |
| Hells | helicase, lymphoid specific | A hypomorphic deletion of helicase domains 3, 4 and part of 2, leads to expression of a C-terminal truncated Hells protein causing an extremely short lifespan. with 60% of homozyogous mutants dying after birth and remaining 40% surviving up to seven weeks (around 25 days) [15105378].
Hells disruption results in genomic hypomethylation, de-repression of silenced genes, and premature aging, characterized by decreased proliferation, increased replicative senescence, and altered expression of Bmi-1 and p16INK4a. Hells mutant exhibit significant hypoglycemia, low birth weight and growth retardation, and signs of premature aging such as greying hair and balding, reduced fat deposition, unstable gait, cachexia, and kyphosis [15105378]. | House mouse |
| NNT1 | Nicotinamide N-methylTransferase 1 | Deletion of NNT1 decreases mean and maximum lifespan by 9 and 19%. 0.5% glucose DR extends the mean and maximum lifespan of NNT1 deletion mutants by 35 and 40%. Overexpression of NNT1 by 5-fold extends mean and maximum replicative lifespan by 18 and 23%, which is approximately of the same magnitude as the lifespan extension obtained from DR. DR in NNT1 overexpression mutant fails to significantly affect the lifespan and only results in extended mean lifespan by 12% and reduced maximum lifespan by 11%. NNT1 overexpression increases rDNA silincing, whereas deletion decreases rDNA silencing. Overexpression of human nicotinamide N-methyltransferase also increases rDNA silencing [12736687]. | Budding yeast |
| NCA3 | Nuclear Control of ATPase 3 | Disruption in NCA3 shortens mean (87% of normal), nut not maximum replicative lifespan without causing any other gross changes in cell cycle parameters of growth characteristics [8810036].
In combination with an NCA2 disruption, NCA3 disruption causes a cryosensitive phenotype on non-fermentable carbon sources due to a defect in the F1-F0 ATP synthetase due to misbalancing of alternate spliceforms of mitochondrial mRNA encoding subunits 6 and 8 of the synthase [7586026]. | Budding yeast |
| HSC80 | — | Deletion of HSC82 has no effect on replicative lifespan, but shortens chronological lifespan [11361336]. | Budding yeast |
| HOG1 | High Osmolarity Glycerol response 1 | Deletion of HOG1 shortens replicative lifespan by 25% and prevents lifespan extension by high osmolarity [12391171]. HOG1 is required for many of the transcriptional responses to high osmolarity, including increased glycerol biosynthesis and MSN2/4-dependent stress response [10722658]. HOG1 deletion slightly decreases chronological lifespan and partially suppresses the premature aging phenotype and short lifespan of ISC1 deletion [22445853]. | Budding yeast |
| HAP5 | Heme Activator Protein 5 | Deletion of HAP5 shortens replicative lifespan by approximately 40%. This is not a premature aging phenotype as "old" HAP5 cells do not become premature sterile or exhibit other biomarkers of yeast aging [9271578]. HAP5 null mutants are unable to grow on a non-fermentable carbon source [7828851]. | Budding yeast |
| GPD1 | Glycerol-3-Phosphate Dehydrogenase 1 | GPD1 deletion shortens replicative lifespan by 25% and prevents lifespan extension by high osmolarity [12391171]. Transcripational regulation of GPD1 by osmotic stress requires HOG1 [8196651]. | Budding yeast |
| GH1 | growth hormone 1 | Mean lifespan in untreated, affected individuals homozyogus for a deletion at the GH1 locus is significantly shorter (P < 0.05) than in affected siblings or the general population. Individuals homozygous for GH1 deletion demonstrate hereditary dwarfism [12915652]. GH1 was found to be associated with longevity [15771611]. | Human |
| Sh | Shaker | Genetic mutation in Sh decreases lifespan by accelerating the aging process. At 25 degree mean and maximum lifespan is reduced by 16 and 22%, while by 18 degree Celsius the reduction is 32 and 21% [8582611]. | Fruit fly |
| Hk | Hyperkinetic | Genetic mutation in Hyperkinetic shortens lifespan through acceleration of the aging process. At 25 degree Celsius mean and maximum lifespan is reduced by 29 and 32%, while by 18 degree Celsius the reduction is 59 and 39% [8582611]. | Fruit fly |
| Pi3K92E | Phosphatidylinositol-3-kinase | Heterozyogous mutation in Pi3K92E fails to extend lifespan [11292874] and it is recessive lethal.
Overexpression of a dominant-negative Pi3K92E (DP110) results in mutants that have impaired regeneration of the intestinal epithelium and are short lived with a reduction of the mean lifespan by 2.8% for males and 5.0% for females [20976250]. | Fruit fly |
| COQ3 | COenzyme Q 3 | Deletion of COQ3 decreases chronological lifespan and renders cells respiratory deficient and sensitive to hydrogen peroxide [12586694]. | Budding yeast |
| ERCC8 | excision repair cross-complementing rodent repair deficiency, complementation group 8 | Individuals with a mutation in ERCC8 (alias CKN1) have a shortened lifespan, short stature, precociously senile appearance, retinal degeneration, optic atrophy, sensitivity to sunlight, and mental retardation [14156156]. Hypertension and renal disease are also common in ERCC8 mutants [514720]. | Human |
| CDC7 | Cell Division Cycle 7 | Transient inactivation of CDC7 results in a shortened replicative lifespan [2698814]. CDC7 participates in silencing and RAS2 modulates its activity [1990268]. | Budding yeast |
| 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 |
| Y47D3A | — | RNAi against Y47D3A.29 decreases mean and maximum lifespan by 19-26% and 34% [18059442]. | Nematode |
| tbp-1 | TATA-Binding Protein | RNAi against tbp-1 decreases mean and maximum lifespan by 15-27% and 21%, respectively [18059442]. | Nematode |
| mpk-1 | MAP Kinase | RNAi against F43C1.2B (encoding mpk-1) decreases mean and maximum lifespan by 8-14% and 14%, respectively [18059442]. | Nematode |
