| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Sh | Shaker | Genetic mutation in Sh decreases lifespan by accelerating the aging process. At 25 degree mean and maximum lifespan is reduced by 16 and 22%, while by 18 degree Celsius the reduction is 32 and 21% [8582611]. | Fruit fly |
| 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 |
| Scgdelta | Sarcoglycan delta | Deletion of Scgdelta has detrimental effects on the flight muscles of adult animals and heart function. Median lifespan is reduced by 15-30% [17855453]. | Fruit fly |
| ry | rosy | Loss-of-function mutation of ry reduces mean lifespan by 45% and maximum lifespan by 35% [17435236]. | Fruit fly |
| rut | rutabaga | Two rutabaga mutants, rut1 and rut2080, have significantly shortened lifespans [17369827]. | Fruit fly |
| rho-7 | rhomboid-7 | rho-7 knockout flies have severe neurological defects and a much reduced lifespan [16713954]. | Fruit fly |
| Rbp9 | RNA-binding protein 9 | Rbp9 mutation significantly decreases longevity with a 33% reduction in median lifespan of males [20589912]. | Fruit fly |
| rb | ruby | Loss-of-function mutation reduces mean lifespan by 33% and maximum lifespan by 22% [17435236]. | Fruit fly |
| Prx5 | Peroxiredoxin 5 | Prx5 overexpression causes an increase in mean and median lifespan under normal conditions. It also leads to a small increase in maximum lifespan.
dprx5(-/-) null mutants are comparatively more susceptible to oxidative stress, have higher incidence of apoptosis, and a shortened mean lifespan, but thee is no significant difference in maximum lifespan (10% survival) [21826223]. | Fruit fly |
| Pi3K92E | Phosphatidylinositol-3-kinase | Heterozyogous mutation in Pi3K92E fails to extend lifespan [11292874] and it is recessive lethal.
Overexpression of a dominant-negative Pi3K92E (DP110) results in mutants that have impaired regeneration of the intestinal epithelium and are short lived with a reduction of the mean lifespan by 2.8% for males and 5.0% for females [20976250]. | Fruit fly |
| pex16 | peroxin 16 | pex16 mutation lead to a reduced mean lifespan of one-third in females and on-fourth in males. The short lifespan can be rescued by the simultaneous overexpression of pex16 in the fat body and differentiated neurons [21826223].
Mutant flies lack normal peroxisomes, have an reduced adult body size (70%-85% smaller than controls) and rozy eyes, show locomotion defects in the development of the nervous system [21826223]. | Fruit fly |
| p53 | — | Overexpression of wild-type p53 during adult life has no significant effect on lifespan. Expression of dominant-negative versions of p53 in adult neurons extends lifespan by 58% in females and by 32% in males and increases resistance to genotoxic stress and resistance to oxidative stress, but not to starvation or heat stress, while not affecting egg production or physical activity.
Dominant negative p53 expression cancels out lifespan extension effect of DR, low calorie-food (5% SY). Muscle or fat body specific expression of a dominant negative form of p53 as well as globally lack of p53 decreases lifespan [16303568]. Loss of p53 activity slightly shortens the lifespan. Mutants that lack p53 survive well up to 50 days, but mortality rate increases relative to wild-type at later ages. p53 mutant animals are extremely sensitive to irradiation [12935877].
Expression of dominant-negative (DN) form of p53 in adult neurons, but not in muscle or fat body cells, extends median lifespan by 19% and maximum lifespan by 8%. The lifespan of dietary-restricted flies is not further extended by simultaneously expressing DN-DMp53 in the nervous system, indicating that a decrease in Dmp53 activity may be part of the DR lifespan-extending effect. Selective expression of DN-Dmp53 in only the 14 insulin-producing cell (IPCs) in the brain extends lifespan to the same extent as expression in all neurons and this lifespan extension is not additive with DR [17686972].
| Fruit fly |
| Nlaz | Neural Lazarillo | Absence of Nlaz, which is homologous to ApoD, results in a reduced lifespan in both sexes. Median lifespan is 30.8% and 22.5% lower in females and males, respectively. Maximum lifespan is reduced by 12% and 30% in females and males [21376794]. | 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 |
| Mnt | CG13316-PC, isoform C | A dMnt null allele results in flies with larger cells, increased weight, and decreased lifespan [16055719]. | Fruit fly |
| Mlp84B | Muscle LIM protein at 84B | RNA interference of Mlp84B specifically in the heart results in bradycardia and heart rthym abnormalities as well as a shorter mean lifespan in males but not in females [18083727]. | Fruit fly |
| mle | maleless | Homozygous mutant animals (mle napts) display a shortened median lifespan and increased frailty in both males and females [18208580]. | Fruit fly |
| mir-277 | — | Constitutive miR-277 expression shortens lifespan and synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype. Transgenic inhibition with a miRNA sponge construct also shortens lifespan [23669073].
miR-277 is downregulated during adult life [23669073].
mir-277 controls branched-chain amino acid catabolism and as a result it can modulate the activity of TOR kinase [23669073]. | Fruit fly |
