| 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 |
| yata | — | yata mutation shortens the maximum lifespan by 68% and results in progressive deterioration of the nervous tissues and aberrant accumulation of Sec23 [19209226]. | Fruit fly |
| VhaSFD | Vacuolar H+-ATPase SFD subunit | Overexpression of VhaSFD (from a doxycycline-inducible promoter) results in a 5-10% increase in mean lifespan [12620118]. | Fruit fly |
| Tsc1 | CG6147-PA Tuberous sclerosis complex genes 1 | Ubiquitously overexpression of UAS constructs (via the daughterless (da)-GAL-4 driver) containing dTSC1 extends mean lifespan at 29°C by 14% [15186745]. | 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 |
| 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 |
| 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 |
| Tor | Target of rapamycin | Expression of a dominant-negative form of Tor extends lifespan [15186745]. Ubiquitious overexpression of dTOR with the da-GAL4 driver of UAS-dTOR(FRB) which contains the 11kDA FKB12-rapamycin binding domain led to a mean and maximum lifespan increase of 15% (24%) and 29% at 29°C and of 50% (26%) and 13% at 25°C, respectively [15186745].
Overexpression of the dominant-negative form of Tor specifically in the fat and muscle tissues is sufficient to extend the mean and maximum lifespan by 24 and 19%, respectively [15186745].
Overexpression of UAS-dTOR(WT) or UAS-dTOR(TED) prevents eclosion to adulthood [15186745]. | Fruit fly |
| 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 |
| tim | timeless | TIMELESS (TIM) oscillation are attenuated in the cerebral clock neurons of elderly flies [23223368].
Tim01 mutants have nearly a 50% reduced fecundity [14667147]. | Fruit fly |
| Thor | — | Null mutation in Thor (alias d4E-BP) causes a significant decrease in longevity (-25% median lifespan in males). Thor is strongly upregulated during starvation. foxo and Thor null mutants are compromised in stress resistant. Stress resistance of foxo null mutants is rescued by Thor overexpression [16055649]. Thor is upregulated on the protein level in a foxo-independent manner upon DR, while it is transcriptional induced in a foxo-dependent fashion by starvation. Thor null mutants cancel out DR-induced lifespan extension, because mutants exhibit a diminished change in lifespan when nutrient conditions were varied. Ubiquitously expression of Thor rescued DR response in females and males. Thor null mutants have a wild-type similar reduction in egg production upon DR. Ubiquitously overexpression of wild-type Thor causes no change under AL, but an activated allele (with more than 3-fold increased binding activity to delF4E) significantly extends lifespan of females (weak allele) and females as well as males (strong allele). Mean lifespan is extended by 11 to 40%. Median lifespan of males and females is enhanced by by 11 and 22%, respectively. Maximum lifespan is extended by 16 and 18% for males and females, respectively. Under DR (0.25% YE) there is no lifespan extension, beyond the effect of DR alone, in all (wild-type, weak and strong) Thor alleles [19804760].
Lifespan of animals with increased Pten and 4E-BP activity in muscle exhibit and extended mean and maximum lifespan by 20% and 15.8% [21111239]. | Fruit fly |
| Tequila | — | Tequila exhibits a coding region difference unique to animals under experimental evolution selected for longevity [23106705].
Tequila is upregulated with age and microbial infection, while downregulated with oxidative stress [11095759; 17196240; 15475297].
| Fruit fly |
| Ten-a | Tenascin accessory | Ten-a exhibits a coding region difference unique to animals under experimental evolution selected for longevity and is differentially expressed in the head in for longevity selected lines [23106705]. | Fruit fly |
| Surf1 | surfeit gene 1 | Surf1 knockdown results in larval lethality. However, knockdown in the central nervous system (CNS) not only bypasses the larval lethality but it results in an increase in maximum lifespan of about 20-30% [16172499]. | Fruit fly |
| sun | Stunted | sun mutations increases lifespan and resistance to oxidative stress [15133470] | Fruit fly |
| sug | sugarbabe | Overexpression of sug (from a doxycycline-inducible promoter) results in a 5-9% increase in mean lifespan [12620118]. | Fruit fly |
| Spargel | — | Tissue-specific overexpression of dPGC-1 in stem and progenitor cells within the digestive tract of females flies extends the mean and maximum lifespan of females by up to 33% and 37%. Those mutants display a delay in the onset of aging-related changes in the intestine, leading to improved tissue homoeostasis in old flies [22055505]. | Fruit fly |
| 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 |
| Sod1 | Superoxide dismutase | Simultaneous overexpression of catalase and Sod (alias Sod1) results in a one-third lifespan extension, a slower rate of mortality acceleration, and a delayed loss in physical performance, but neither has any effect on lifespan alone [8108730]. General overexpression of Sod (also known as Cu/ZnSOD) alone is sufficient to extend lifespan by up to 48%. Simultaneous overexpression of catalase with Cu/ZnSOD has no added benefit, presumably due to a pre-existing excess of catalase [9858546]. Sod1 reduction by knockdown or knockout blunts the lifespan extension by a high sugar-low protein diet, but not a low-calorie diet [22672579].
Sod mutant flies display infertility and a reduction in lifespan [2539600]. | Fruit fly |
| snz | snazarus | Mutation in snz increases maximum lifespan of both sexes by up to 66%, while the median female lifespan is approximately 85% higher and that of males around 72% [18478054]. | Fruit fly |
| SNF4Agamma | SNF4/AMP-activated protein kinase gamma subunit | Deletion of SNF4Agamma from the first day of the imaginal stage shortens mean lifespan by 23% and causes morphological and behavioural features of premature aging [18219227]. | Fruit fly |
| sm | smooth | Overexpression of sm in males increases mean and maximum lifespan by 29% and and 16%, respectively [22366109]. | Fruit fly |
| Sirt6 | — | Decreased expression of Sirt6 by RNA interference causes lethality during development. Sirt6 silencing in neurons shortens mean lifespan by 20% [17159295]. | Fruit fly |
| Sirt2 | — | Decreased expression of Sirt2 by RNA interference causes lethality during development. Silencing in neurons shortened mean lifespan by 20% [17159295]. | Fruit fly |
| Sir2 | — | Overexpression of Sir2 (alias dSir2) extends lifespan by up to 57% and specifically median lifespan by 40-60%, whereas a decrease in Sir2 activity by mutation blocks the life-extending effect of caloric reduction or rpd3 mutations [15520384]. rpd3 mutants fed normal food and wild-type fed a low-calorie diet increase dSir2 expression two-fold [12459580]. Sir2 mutation does not reduce lifespan under AL. Ubiquitous Sir2 overexpression causes a 4-fold increase in Sir2 mRNA expression and an up to 57% increase in average lifespan (29% for females and 18% for males). A 10 - 20% increase in Sir2 mRNA levels causes no lifespan extension. High levels of Sir2 protein is found in nuclei of neurons and in nuclei and cytoplasm of fat body cells. Neuronal Sir2 overexpression extends average lifespan by 52% in females and 20% in males. Motor-neuronal specific expression fails to cause lifespan extension. Flies with no or with several decreased Sir2 gene function have no lifespan extension under DR. DR fails to cause further increase in lifespan or even reduces lifespan toward normal of Sir2 overexpression mutants. Mild Sir2 overexpression in the fat-body extends lifespan and reduces relative body fat content in both males and females [22661237].
Sir2 in the adult fat body regulates longevity in a diet-depending manner. A diet-dependent lifespan phenotype of Sir2 perturbations (both knockdown and overexpression) in the fat-body, but not in muscles, negates the effects of background genetic mutants. Sir2 knockdown abrogates fat-body dFoxo-dependent lifespan extension [23246004].
Decreased expression of Sir2 and Sir2-like genes in all cells causes lethality during development. Suppression of the Sir2 in neurons decreases the median lifespan by 10-30%, while ubiquitinous silinecing of the Sir2-like genes shortens lifespan. The effects are server at 28°C that at 25°C [17159295]. | Fruit fly |
