| ZTA1 | Zeta-crystallin homolog, found in the cytoplasm and nucleus; has similarity to E. coli quinone oxidoreductase and to human zeta-crystallin, which has quinone oxidoreductase activity | Deletion of ZTA1 increases replicative lifespan by 15% in the alpha strain and decreased by 10% in the a strain [18340043]. Although ZTA1 was identified as a potential long-lived mutant strain in a bar-code screen, deletion of ZTA1 does not significantly affect chronological lifespan under starvation/extreme DR [20657825]. | Budding yeast |
| WRN | Werner syndrome, RecQ helicase-like | Mutation in WRN causes Werner Syndrome which characteristics includes prematurely aged facies, scleroderma-like skin changes, cataracts, arteriosclerosis, subcutaneous calcification, and diabetes mellitus [McKusick et al. 1963; 5327241]. Inheritance is autosomal recessive and malignancy is frequent. THe frequency is 3 per million individuals in Japan [7460386].
Cells from a Werner heterozygote exit the cell cycle at a faster rate than do normal cells [8265666]. Loss of WRN promoter aberrant mitotic recombination [11316787].
The single nucleotide polymorphism rs1800392 in WRN has been associated with exceptional longevity in a plethora of genetic signatures [22279548]. WRN was found to be associated with longevity [10069711; 20855428; 20855428; 20855428 ;17903295; 22406557; 16405962; 16405962; 16405962; 20855428; 20855428; 20855428; 22279548]. WRN was found to be associated with longevity [24244950]. | Human |
| Ucp3 | uncoupling protein 3 (mitochondrial, proton carrier) | Metabolic intensity (daily food energy/body mass) correlates with longevity in MF1 mice. The animals with the highest quartile of metabolic intensities have a mean lifespan of 36% longer than animals with the lowest quartile of metabolic intensities. The highest metabolism of long-lived animals can be attributed to increased uncoupling Ucp3 [15153176].
Skeletal muscle mitochondria isolated from high metabolism mice are more uncoupled that those from low metabolism mice [15153176]. | House mouse |
| unc-51 | UNCoordinated-51 | unc-51(e369) mutation reduces mean but extends maximum lifespan. unc-51(e369) mutation reduces lifespan of eat-2(ad1116) mutants to that of wild-type [18219227]. | Nematode |
| UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCHL1 is assoicated with Parkinson's disease [9774100]. UCHL1 belongs to a family of de-ubiquitinating enzymes responsible for the hydrolysis of bonds between ubiquitin molecules and small adducts [11084366]. Decreased activity due to mutation may result in decreased labeling of abnormal proteins for clearance. | Human |
| TAD1 | tRNA-specific Adenosine Deaminase 1 | Deletion of TAD1 does non-significantly increase the mean replicative lifespan by 14% [20550517]. | Budding yeast |
| tps-2 | Trehalose 6-Phosphate Synthase 2 | RNA interference mediated inactivation of the trehalose-biosynthetic gene trehalose-6-phosphate synthase-2 (tps-2) decreases daf-2 mutant's long lifespan [20477758]. | Nematode |
| tps-1 | Trehalose 6-Phosphate Synthase 1 | RNA interference mediated inactivation of the trehalose-biosynthetic gene trehalose-6-phosphate synthase-1 (tps-1) decreases daf-2 mutant's long lifespan [20477758]. | Nematode |
| GCN4 | Transcriptional activator of amino acid biosynthetic genes in response to amino acid starvation; expression is tightly regulated at both the transcriptional and translational levels | Deletion of GCN4 increases the replicative lifespan by 10% in the alpha strain [19030232].
GCN4 deletion decreases the lifespan in the alpha and a strain [20657825].
The chronological lifespan of GCN4 deletion is strongly decreased in the a strain [20421943]. | Budding yeast |
| TSHR | thyroid stimulating hormone receptor | Two single nucleotide in the TSHR were associated with increased TSH in both centenarians and their offspring [19837933].TSHR was found to be associated with longevity [19837933]. TSHR was not found to be associated with longevity [19837933]. | Human |
| Trxr-1 | Thioredoxin reductase-1 | Overexpression of Trxr-1 (alias GSR; glutathione reductase) in transgenic flies results in increased lifespan and oxidative stress resistance, but only under hyperoxia [10506576]. | Fruit fly |
| tert | telomerase reverse transcriptase | First-generation tert(-/-) zebrafish die prematurely with shorter telomeres. tert(-/-) fish develop degenerative phenotypes, including premature infertility, gastrointestinal atrophy, and sarcopenia. tert(-/-) mutants have impaired cell proliferation, accumulation of DNA damage markers, and a p53 response leading to early apoptosis, followed by accumulation of senescence cells. Apoptosis is primarily observed in the proliferative niche and germ cells. Cell proliferation, but not apoptosis, is rescued in tp53(-/-)tert(-/-) mutants, underscoring p53 as mediator of telomerase deficiency and consequent telomere instability [http://denigma.de/url/3p]. | Zebrafish |
| tbc-7 | TBC (Tre-2/Bub2/Cdc16) domain family | RNA interference of tbc-7 decreased median lifespan by 28% in daf-2 mutants [18006689]. | Nematode |
| TPK2 | Takashi's Protein Kinase 2 | Deletion of TPK2 in a tpk1 and tpk3 double mutant background decreases PKA activity and extends replicative lifespan by approximately 25% in SGY446 strain [11000115]. | Budding yeast |
| SML1 | Suppressor of Mec1 Lethality 1 | Deletion of SML1 increases non-significantly mean replicative lifespan by 3% and non-significantly maximum lifespan by 16% [20550517]. | Budding yeast |
| SOD1 | SuperOxide Dismutase 1 | The overexpression of Sods, mitochondrial Sod2 and cytosolic CuZnSod (Sod1), in combination delays the age-dependent reversible inactivation of mitochondrial aconitase, a superoxide-sensitive enzyme, and extends chronological lifespan by 30% [12586694]. Deletion of SOD1 decreases replicative lifespan by 40% [17460215]. Overexpression of SOD1 with CCS1 levuates the level of Cn, Zn-Sod activity and increased chronological lifespan. However overexpression of SOD1 without high cooper or simultonous overexpression of CCS1 shortened both chronological and replicative lifespan [15659212]. Overexpression of SOD1 has no effect on replicative lifespan [10224252]. Deletion of SOD1 shortens replicative lifespan by approximately 40%. The magnitude of the decrease in lifespan does not appear to dependent on oxygen concentration in the atmosphere [12020810]. Deletion of SOD1 shortens replicative lifespan [10547026]. Deletion of SOD1 shortens replicative as well as chronological lifespan [10222047].
Cells with a deletion of SOD1 exhibit a profound defect in entry into and survival during stationary phase (i.e. chronological lifespan) in the W303-B strain [8647826; 10222047], which is partially suppressed by expression of human Bcl-2 [9199172].
Hypersensitivity to oxygene and significantly decreased replicative lifespan of SOD1 deletion can be ameliorated by exogenous ascorbate. If acorbate's negative effects of auto-oxidation are prevented by exchange of medium, ascorbate prolongs mean and maximum replicative lifespan in the atmosphere of air and pure oxygene [15621721].
SOD1 deletion causes sensitivity to hyperoxia as well as methionine and lysine auxotrohies [9199172].
| Budding yeast |
| SST | Somastatin | Two with age-related differential methylation markers lay within Somastatin (SST) [23177740] which declines with age and is linked to Alzheimer's disease [15778722]. | Human |
| Sirt1 | sirtuin 1 (silent mating type information regulation 2, homolog) 1 (S. cerevisiae) | Whole-body deletion of Sirt1 in the adulthood results in mice which are seemingly normal in every way. When mice were given low doses of resveratrol after Sirt1 was disabled, there were no discernible improvement in mitochondrial function or any parameter, while mice with normal Sirt1 function given reservatrol showed dramatic increases in energy, mitochondrial biogenesis and function, AMPK activation and increased NAD+ levels in skeletal muscle. When mice lacking Sirt1 were given low doses of reserveratrol, AMPK was unaffected. When doses were significantly increased in these mice, AMPK was activated in a SIRT1-indepent manner, but still no benefit to mitochondrial function resulted [22560220]. Sirt1 overexpression mimicks the effect on reservatrol on mitochondrial function, but failed to extend lifespan [22560220].
SIRT1 knock-out mouse embryonic fibroblasts (MEFs) have a significant greater replicative capacity in culture. p19ARF levels are significantly reduced in SIRT1 knock-out MEFs [16054100].
Sirt1-null mice do not exhibit lifespan extension upon Dietary Restriction [18335035].
Sirt1 is required for high-magnitude circadian transcription of several core clock genes. It deacetylates Per2, Arntl and histones of clock-controlled genes [18662546].
SIRT1 directly [21187328] and indirectly [20450879] prevents telomere shortening. | House mouse |
| sbds-1 | Shwachman-Bodian-Diamond Syndrome protein homolog 1 | RNA interference of sbds-1 decreases median lifespan by 24% in daf-2 mutants [18006689]. RNAi knockdown of sbds-1 starting at hatching or only during the adulthood significantly decreases lifespan of eat-2 without affecting wild-type lifespan. SBDS-1 are elevated in eat-2 mutants. Increased content of SBDS-1 is, at least partially, required for lifespan-extension by DR [22810224]. | Nematode |
| sgg | shaggy | Several insertions of P-based vectors in the structural part of sgg are associated with alterations of male and female lifespan [22661237]. | Fruit fly |
| SAG12 | senescence-associated protein 12 | Expression of SAG12 is specifically activated by developmentally controlled senescence pathways but not by stress- or hormone-controlled pathways [10579486; 10579487]. | — |
| RTG2 | ReTroGrade regulation 2 | RTG2 is required for replicative lifespan extension associated with the retrograde response, a pathway that signals the functional status of mitochondria to the nucleus to regulate the expression of several genes [11024000]. RTG2 is not required for replicative lifespan extension by DR [11024000].
RTG2 null mutants are not petite [8422683], but display various nutrient auxotrphies and alterations of carbohydrate metabolism [7727418]. | Budding yeast |
| Rae1 | RAE1 RNA export 1 homolog (S. pombe) | Haploinsufficiency of Bub3 and Rae1, but not haploinsufficiency of either gene by itself, reduces lifespan by 12% and appears to accelerate ageing. | House mouse |
| PPG1 | Protein Phosphatase involved in Glycogen accumulation 1 | PPG1 deletion reduces significantly mean chronological lifespan under starvation/extreme DR [20657825]. | Budding yeast |
| PSEN1 | presenilin 1 | Mutations (more than 60 different) in PSEN1 are associated with Alzheimer's disease, of which all result in increased production of abnormally long amyloid beta-protein and an increase in senile plaque formation [10934557].PSEN1 was found to be associated with longevity [17903295]. | Human |
