| ubc-18 | UBiquitin Conjugating enzyme 18 | ubc-18 overexpression is unable to extend lifespan (possibly, UBC-18 is not limiting for WWP-1 function in lifespan). Loss of ubc-18 function by mutation or RNAi reduces lifespan at 25 degree Celsius, but only slightly at 20 degree Celsius. RNAi depletion of ubc-18 completely suppresses increased longevity of eat-2 mutants. RNAi depletion of ubc-18 has no effect on long lifespan of isp-1 or daf-2 mutants. Combined knockdown of wwp-1 and ubc-18 by RNAi does not shorten lifespan any further than RNAi of either single gene. Knockdown of ubc-18 suppresses extended lifespan of wwp-1 overexpression [19553937]. | Nematode |
| TPS1 | Trehalose-6-Phosphate Synthase 1 | Deletion of TPS1 decreases intracellular trehalose concentration and shortens the mean chronological lifespan by 74% (at 30 degree Celsus in BY4742) [22783207]. | Budding yeast |
| TEC1 | Transposon Enhancement Control 1 | Tec1 is a positive regulator of chronological lifespan. Absence of TEC1 causes a significant shortened chronological lifespan, but does not block chronological lifespan extension by rapamycin. TEC(AxY) mutation also reduces chronological lifespan, although not so pronounced as strains lacking TEC1. Rapamycin-induced chronological lifespan extension is almost completely blocked by TEC(AxY) allele [21840851]. | Budding yeast |
| TAE2 | Translation Associated Element 2 | TAE2 deletion decreases replicative lifespan by 30% in the a strain [18340043]. | Budding yeast |
| Trp63 | Transformation related protein 63 | Heterozygous Trp632 mutant mice have a shortened lifespan (by 21.5%) and display features of accelerated aging [16107615].
The decreased longevity in Trp63(+/-) mice is almost identical to that of Trp53(+/m) mice in which enhanced Trp53 activity provides resistance to spontaneous tumors while simultaneously accelerating aging [16107615]. Trp63(+/-) are not susceptible to spontaneous tumors [16107615]. | House mouse |
| 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 |
| 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 |
| TDA5 | Topoisomerase I Damage Affected 5 | Deletion of TDA5 decreases replicative lifespan by 30% in the alpha strain [19030232]. | Budding yeast |
| Top3b | Topoisomerase (DNA) III beta | Homozygous disruption of Top3b results in a normal development but a shorter lifespan (by approximately 70%) accompanied by lesions in multiple organs in C57BL/6 [11331780].
Yeast Top3 physically interacts with Sgs1 [7969174]. Human TOP3A interacts with BLM [10734115; 10728666] and both TOP3A and TOP3B interact with RECQ5 [10710432]. | House mouse |
| Trx-2 | thioredoxin-2 | Trx-2 mutants have a 25% reduction in maximum lifespan and exhibit lower tolerance to oxidative stress while animals carrying multiple copies of Trx-2 exhibit higher tolerance [17567437]. | Fruit fly |
| trx-1 | ThioRedoXin 1 | Thioredoxins regulate many cellular redox processes. trx-1 is mainly associated with neurons and is expressed in ASJ ciliated sensory neurons and to some extent also on the posterior-most internal cells. trx-1 reduces protein disulfides in the presence of a heterologous thioredoxin reductase. trx-1 null mutant display reduced mean and maximum lifespan [16387300]. Mutants with a deletion in the trx-1 gene display a decrease in lifespan and are sensitive to oxidative stress [16324156]. trx-1 overexpression extends lifespan in wild-type but not in eat-2 mutants. trx-1 deletion completely suppresses the lifespan extension caused by eat-2 mutation, but only partially suppresses that by daf-2 or osm-5 mutations. Ectopic expression of trx-1 in ASJ neurons (but not in the intestine) in trx-1 mutants rescues the lifespan-extension conferred by eat-2 mutation. trx-1 overexpression extends lifespan of wild-type but not in eat-2 mutants. trx-1 deletion almost completely suppresses lifespan extension induced by dietary deprivation (DD). DD upregulates trx-1 expression in ASJ neurons. DR activates trx-1 in ASJ neurons which in turn triggers a trx-1-dependent non-cell autonomous mechanism to extend adult lifespan [21334311].
| Nematode |
| TSA1 | Thiol-Specific Antioxidant 1 | A gain-of-function allele of peroxiredoxin (thioredoxin peroxidase, Tsa1) causes a dominant oxidative stress-resistance and robust premature aging phenotype with reduced mean lifespan. These effect is not provoked by altered Tsa1 levels, nor can it be stimulated by deletion, haploinssufficiency or overexpression of wild-type allele [20729566]. Disruption of TSA1 shortens chronological lifespan [15129730]. Replicative lifespan extension by DR in sir2;fob1 double mutant is reduced by TSA1 deletion mutant. Wild-type cells require TSA1 to fully extend lifespan. Mutation in CDC35 (adenylate cyclase), a genetic mimetic of DR, is dependent on TSA1 to extend lifespan [21884982]. | Budding yeast |
| Terc | telomerase RNA component | Telomerase null mice exhibit age-dependent telomere shortening and shortened lifespan with succeeding generations. Median lifespan is reduced by 26% in G6 Terc(-/-) mice compared to wild-type or G1-G3 Terc(-/-) (18 months vs. 24 months). G6 Tec(-/-) display hair greying, hair loss, and ulcerative skin lesions, as well as impaired response to wound healing and hematoitopitic ablation, and an increased incidence of cancer [10089885]. Cells from Terc(-/-) mice (G4 and upward) exhibit chromosomes lacking detectable teloemre repeats, aneuplody, and end-to-end fusions [9335332]. | House mouse |
| 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 |
| tbp-1 | TATA-Binding Protein | RNAi against tbp-1 decreases mean and maximum lifespan by 15-27% and 21%, respectively [18059442]. | Nematode |
| 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 |
| Sod2 | Superoxide dismutase 2 (Mn) | RNA interference of Sod2 results in increased oxidative stress and early-onset mortality in young adults [12456885]. Overexpression of Sod2 by 5-115% decreases lifespan by 4-5% without any compensatory changes in metablic rate, level of physical activity, or the levels of other antioxidants (Sod, Cat, and glutathione) [10545213]. Targeted overexpression of Sod2 in motor neurons alone extends lifespan by 30% [11113599]. Induced overexpression of Sod2 in adult animals extends lifespan up to 37% [12072463]. Overexpression of catalase in combination with SOD2 has no added benefit for lifespan [12072463]. Animals overexpressing SOD2 or catalase do not exhibit a decrease in metabolism as measured by oxgen consumption [12072463].
Sod2 overexpression results in a 20% increase in mean and maximum lifespan [18067683]. | Fruit fly |
| SOD2 | SuperOxide Dismutase 2 | SOD2 deletion decreases replicative lifespan by 72% [17460215]. SOD2 deletion decreases chronological lifespan [21076178]. Deletion of SOD2 decreases chronological lifespan in wild-type and abolishes chronological lifespan extension in sch9Delta mutants as well as decreases chronological lifespan in cyr1:mTn mutants [12586694]. Combined overexpression of SOD1 and SOD2 extends chronological lifespan by 30% in EG103 strain [12586694].
SOD2 deletion mutants are hypersensitive to oxygen and grow poorly in ethanol [10222047]. | 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 |
| 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 |
| SdhB | Succinate dehydrogenase B | SdhB mutants are hypersensitive to oxygen and displays signs of premature aging, including a 66% decrease in mean lifespan and a 17% decrease in maximum lifespan [17056719]. | Fruit fly |
| YKU80 | Subunit of the telomeric Ku complex (Yku70p-Yku80p) | Deletion of YKU80 significantly shortens replicative lifespan, but does not accelerate the normal aging process [10521401]. YKU80 null mutant is defective for non-homologous end-joining [8754818] and for telomere silincing [9501103; 9635192] | Budding yeast |
| 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 |
| PHB2 | Subunit of the prohibitin complex (Phb1p-Phb2p), a 1.2 MDa ring-shaped inner mitochondrial membrane chaperone that stabilizes newly synthesized proteins; determinant of replicative life span; involved in mitochondrial segregation | PHB2 deletion leads to a slight reduction in both mean and maximum replicative lifespan, and when both PHB1 and PHB2 genes are deleted, the mean replicative lifespan is reduced by 40% [9259555]. Deletion of PHB2 decreases replicative lifespan by 30% [12882345]. Phenotypic changes characteristic of aging cells (e.g. lengthening of cell cycle and specific morphological changes) suggests that PHB1;PHB2 double mutants undergo premature aging, not simply reduction of viability [9259555].
PHB2 mutants exhibit no reduction in stress resistance or bulk growth rate. PHB1;PHB2 double mutant have a strong defect in mitochondrial potential [9259555].
Prohibitin-dependent mutation pbd1 and pdb2 behave in a different manner and probaly affect different aspects of prohibitin function. pdb1 mutants slightly extended lifespan by 11%, whereas in contrast, the pdb2 mutation results in a shortening in both the mean- and the maximum-lifespan (by 28 and 17%, respectively). pdb1 mutation also reduces chronological lifespan. Reducing the expression of the PHB2 in the pbd mutants retards the rate of growth and affects replicative lifespan [16710639]. | Budding yeast |
| Stub1 | STIP1 homology and U-Box containing protein 1 | Knock-out mice exhibited a deregulation of protein quality control accompanied by a short lifespan and accelerated age-related pathophysiological features. | House mouse |
