| PGRP-LF | Peptidoglycan recognition protein LF | Overexpression of PGRP-LF increases mean and maximum lifespan by 13% and 24% [22366109]. | Fruit fly |
| CG30427 | — | Overexpression of CG30427 in males increases mean lifespan by 18% [22366109]. | Fruit fly |
| CG10383 | — | Overexpression of CG10383 in males increases mean and maximum lifespan by 12% and 8%, respectively [22366109]. | Fruit fly |
| SIFR | SIFamide receptor | Overexpression of SIFR in males extends mean and maximum lifespan by 23% and 3%, respectively [22366109]. | Fruit fly |
| sm | smooth | Overexpression of sm in males increases mean and maximum lifespan by 29% and and 16%, respectively [22366109]. | Fruit fly |
| Sin3A | — | Overexpression of Sin3A increases mean and maximum lifespan by 13% and 3%, respectively [22366109]. | Fruit fly |
| mir-34 | — | mir-34 loss triggers a gene expression profile of accelerated brain aging, late-onset brain degeneration and catastrophic decline in survival, while mir-34 upregulation extends median lifespan and mitigated neurodegeneration induced by polyglutamine. | Fruit fly |
| Cbs | — | Ubiquitous or neuron-specific transgenic overexpression of Cbs enhances longevity in fully-fed animals. Cbs RNAi partially abrogates increased lifespan by DR, but has no effect on fully fed animals. Cbs upregulation is required for increased lifespan under low-nutrient conditions. Response of male flies to DR is muted in comparison with females. Adult-specific ubiquitous expression of Cbs is sufficient to increase female mean and maximum lifespan by 12 - 43% and 10%, respectively. Males, whose lifespan is relatively less affected by DR, exhibite a smaller, but still significant increase in lifespan by 7% upon Cbs overexpression. Neuronal overexpression also increases lifespan, albeit modestly (approximately 12% mean and 15% maximum lifespan extension), whereas overexpression in the fat body and in the gut has no effect [21930912]. | Fruit fly |
| ImpL2 | Ecdysone-inducible gene L2 | Lmp-L2 over-expression, ubiquitous or restricted to DILP-producing cells and/or gut and fat body, extends lifespan even if induced at adult onset [21108726]. Overexpression of ImpL2 increases mean and maximum lifespan by 15% and 23%, respectively. Lifespan is reduced when Impl2 is strongly over-expressed throughout the adult by the conditional GS driver, act-GS-GAL4 or da-GS-Gal3, while restricted over-expression of the ImpL2 in fat cells by using S106-GS-Gal4, which increases mRNA level about 6-fold extends lifespan in both sexes [22366109]. mRNA for Impl2 was strongly elevated in sterile, long-lived flies [18434551]. | 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 |
| 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 |
| sug | sugarbabe | Overexpression of sug (from a doxycycline-inducible promoter) results in a 5-9% increase in mean lifespan [12620118]. | 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 |
| 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 |
| Rdh | Red herring | Overexpression of Rdh from a doxycycline-inducible promoter results in a 6-17% increase in mean lifespan [12620118].
Rdh is an open reading frame in the first intron of the encore gene [12620118]. | Fruit fly |
| POSH | Plenty of SH3s | Neural-specific overexpression of POSH extends the mean lifespan of adult flies by 14% at 25°C. Ectopic expression of POSH during development results in morphological abnormalities [11868902]. | Fruit fly |
| Pka-C1 | cAMP-dependent protein kinase 1 | PKA-overexpressing flies (hsPKA*/+) have an about 30% extended maximum lifespan [17369827]. | Fruit fly |
| Pcmt | Protein-L-isoaspartate (D-aspartate) O-methyltransferase | Overexpression of Pcmt extends lifespan by 32-39% at 29 degrees but not at 25 degrees [11742076].
The adult lifespan of animals overexpressing Pcmt is extended [18772467]. | Fruit fly |
| NF1 | Neurofibromin 1 | NF1 mutants have a shortened lifespan and exhibited increased vulnerability to heat and oxidative stress as well as reduced mitochondrial respiration and elevated ROS production. Overexpression of NF1 increases mitochondrial respiration and reduced ROS production. It increases mean lifespan by 49% in males and 68% in females and maximum lifespan by 38% in males and 52% in females. It also improved reproductive fitness [17369827]. | Fruit fly |
| mys | myospheroid | mys mutants exhibit ameliorated age-related declines in locomotor activity and an increase in mean lifespan of 20% [14570233]. | Fruit fly |
| Hsp70Bc | Heat-shock-protein-70Bb | Overexpression of the Hsp70 locus (containing Hsp70Bb and Hsp70Bc) in transgenic flies extends lifespan as much as 7.9% [9363888]. | Fruit fly |
| Hsp68 | Heat shock protein 68 | Overexpression of Hsp68 extends modestly (by around 15%) median and maximum lifespan [14602080]. Hsp68 is activated by the JNK pathway and target gene of foxo [20976250].
There is a consistent and significant lifespan extension by 20% in both males and females when hsp68 is overexpressed in somatic cells. hsp68 overexpression using GMR-Gal4, and eye-specific driver that expresses Gal4 in salivary glands has no effects. Hsp78 overexpression using the weaker 5961FS driver moderately but significantly extends lifespan [20976250]. | Fruit fly |
