| Zw | Zwischenferment | Mean lifespan of G6PD overexpressor flies is extended in comparison with driver and responder controls, armadillo-GAL4 (up to 38%), Tubulin-GAL4 (up to 29%), C23-GAL4 (up to 27%), da-GAL4 (up to 24%), D42-GAL4 (up to 18%) and Appl-GAL4 (up to 16%). The maximum lifespan is also increased [18809674].
G6PD enzymatic activity as well as levels of NADPH, NADH, and the GSH/GSSG ration are increased [18809674]. | Fruit fly |
| Yaf2 | YY1 associated factor 2 | Yaf2 is transcriptional upregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. | Norway rat |
| YTHDF2 | YTH domain family, member 2 | A locus associated with human longevity corresponds to (TG)n microsatellite is located in the YTHDF2 gene. 412 participants of different ages, including 137 centenarians, were genotyped. The increased homozygosity in centenarians at this locus was confirmed, and observed a concomitantly increased frequency of the most frequent allele and the corresponding homozygous genotype. The same genotype was associated with increased YTHDF2 messenger RNA levels in immortalized lymphocytes. [16799135].YTHDF2 was found to be associated with longevity [16799135]. | Human |
| XDH | xanthine dehydrogenase | XDH was found to be associated with longevity [22406557; 22279548]. | Human |
| XRCC6 | X-ray repair complementing defective repair in Chinese hamster cells 6 | The single-nucleotide polymorphism in rs132793 in XRCC6 has significant effect on telomere length, but it is not associated with longevity [21972126]. | Human |
| XRCC5 | X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining) | XRCC5 was found to be associated with longevity [22406557; 16518718]. | Human |
| XRCC4 | X-ray repair complementing defective repair in Chinese hamster cells 4 | XRCC4 was found to be associated with longevity [16518718]. | Human |
| XRCC3 | X-ray repair complementing defective repair in Chinese hamster cells 3 | XRCC3 was found to be associated with longevity [16518718]. | Human |
| XRCC1 | X-ray repair complementing defective repair in Chinese hamster cells 1 | XRCC1 was found to be associated with longevity [16518718]. | Human |
| 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 |
| UCP2 | uncoupling protein 2 (mitochondrial, proton carrier) | Overexpression of human UCP2 in the fly nervous system extends lifespan by 10-30%. Ubiquitous overexpression is lethal [16054055]. | Human |
| TH | tyrosine hydroxylase | Polymorphyc repeats in intron 1 (Short and Long alleles) of the TH gene were examined in 196 centenarians (143 females and 53 males) and 358 controls (196 females and 162 male; 10-85 years old). A significant loss of LL homozygous genotypes was found at the THO locus in male but not in female centenarians with respect to matched controls [9887369].TH was found to be associated with longevity [12297342]. TH was found to be associated with longevity [21407269]. TH was found to be associated with longevity [19367319]. TH was not found to be associated with longevity [19367319]. TH was found to be associated with longevity [11053670]. TH was found to be associated with longevity [17989723]. | Human |
| TNF | tumor necrosis factor | The frequency of the -308 polymorphism in the TNF gene was analyzed in 71 healthy elders, aged 80 to 96 years (mean 86.2 years). The control samples were obtained from 99 young (from 21 - 54 years; mean 35.2 years) healthy individuals unrelated to elders were studied, age ranged from 80 to 96 years (mean 86.2 years). The TNF2 allele was increased in the elder group when compared to young controls [16269080].TNF was found to be associated with longevity [20518833]. TNF was found to be associated with longevity [18511747]. TNF was found to be associated with longevity [12714268]. TNF was found to be associated with longevity [12714268]. TNF was found to be associated with longevity [12676903]. TNF was found to be associated with longevity [11640949]. TNF was found to be associated with longevity [21299522]. TNF was found to be associated with longevity [21299522]. TNF was not found to be associated with longevity [12676903]. TNF was found to be associated with longevity [16269080]. TNF was not found to be associated with longevity [11640949]. | Human |
| TUBB4B | tubulin, beta 2C | TUBB4B was found to be associated with longevity [22174011]. | Human |
| ttll-9 | Tubulin Tyrosine Ligase Like | Knockdown of ttll-9 throughout the entire life increases the lifespan by 3% [23698443]. | Nematode |
| TOMM40 | translocase of outer mitochondrial membrane 40 homolog (yeast) | TOMM440 correlates substantial with longevity and has been associated with Alzheimer's disease [22279548].
rs4420638 at TOMM40 gene locus exhibits significant association with longevity p-value = 9.6x10^-8). Combined modeling of linkage and association shows that association of longevity with APOEepsilon4 and APOEepsilon2 alleles explain the linkage at 19q1.11-q13.32 with pvalue-0.02 and p-value=1.0x10^-5, respectively [23286790]. TOMM40 was found to be associated with longevity [21418511; 23040522; 22279548]. TOMM40 was not found to be associated with longevity [24924924]. TOMM40 was found to be associated with longevity [24924924]. | Human |
| TGFB1 | transforming growth factor, beta 1 | 4 SNPs (-800 G/A, -509 C/T, +869 T/C and +915 G/C) in the TGFB1 gene were analysed in 419 subjects from Northern and Central Italy, including 172 centenarians and 247 younger controls. Significant differences were found at the +915 site as far as the C allele and GC genotype were concerned, both of them being lower in centenarians than in young controls, but none of the other tested genetic variants was significantly different between centenarians and controls. Moreover, a particular haplotype combination (G -800/C -509/C 869/C 915) was notably lower in centenarians than in younger individuals [15569360].TGFB1 was found to be associated with longevity [21299522]. TGFB1 was found to be associated with longevity [21299522]. TGFB1 was found to be associated with longevity [15569360]. | Human |
| 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 |
| TLR4 | toll-like receptor 4 | The ASP299GLY ploymorphism in the TLR4 gene shows a significantly lower frequency in patients affected by myocardial infarction compared to controls, whereas centenarians exhibit a higher frequency [16803999]. TLR4 was found to be associated with longevity [16803999; 17493663].TLR4 was found to be associated with longevity [17493663]. TLR4 was not found to be associated with longevity [17493663]. | Human |
| 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 |
| 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 |
| TrxT | Thioredoxin T | Overexpression of TrxT in neurons increases the level of locomotor activity in aged flies and extends the mean lifespan by 15% [17301052]. | Fruit fly |
| Jafrac1 | thioredoxin peroxidase 1 | Neuronal overexpression of Jafrac1 significantly increases both mean and maximum lifespan, while neuronal knockdown as well as loss of function mutation, causes a reduction in lifespan by 30%. The mean lifespan is 26% and 29% higher in females and males, respectively. The maximum lifespan is increased by 22% and 26% in females and males, respectively [19720829].
There is a consistent and significant lifespan extension (15% mean lifespan increase) in both males and females when Jafrac1 is overexpressed in somatic cells. Jafrac1 overexpression using the weaker 5961FS driver moderately but significantly extends lifespan [20976250]. | 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 |
| to | TakeOut | Overexpression of to in adult neurons, pericerbral or abdonimal fat body increases male and female lifespan. to overexpression in the adult nervous system, head fat body and abdominal fat body results in 25, 20 and 12-18% increase of mean lifespan. On average the mean lifespan is extended for males and females by 18 and 26%, while maximum lifespan of male and female is increased by 13 and 25% [20519778].
Starvation, DR and many longevity mutants (like Rpd3, Sir2, chico, methusalem) all upregulate takeout (to). to is a secreted potential juvenile hormone binding protein and its induction by starvation is blocked by all arrhythmic central clock mutants [20519778; 20622267]. | Fruit fly |
