| Dys | Dystroglycan | Loss of dys function in the heart leads to an age-dependent disruption of the myofibrillar organization within the myocardium as well as to alterations in cardiac performance. dys RNAi-mediated knockdown in the mesoderm also shortens lifespan. Mesodermal dys knockout results in a morderate maximum lifespan reduction (13%), but not when exclusively targeted to the heart. In contrast, half of the transheteozygous DysExel618/Dyskx43 deficiency flies die at 29 days compared to 63 days in controls. This indicates that a moderate dye loss-of-function in all muscles, but not in just the heart, reduces the normal lifespan [18221418]. | Fruit fly |
| Lnk | — | Loss of Lnk function results in increased median (14% in females and 17.5 in males) and maximum lifespan, reduced female fecundity and improves survival under conditions of oxidative stress and starvation. Heterozygousity does not result in any significant differences in lifespan in either males or females. Moreover, lifespan extension in one of the female homozygous mutant is fully rescued by the introduction of a Lnk genomic rescue construct [20333234]. | Fruit fly |
| g | garnet | Loss-of-function mutation in g reduces mean lifespan by 11 - 42% and maximum lifespan by 7 - 30% [17435236]. | Fruit fly |
| Orco | Odorant receptor co-receptor | Loss-of-function mutation in Orco (alias Or83b) results in olfactory defects, altered adult metabolism, enhanced stress resistance, and life-extension. Fully fed female homozygous Or83b null mutants exhibit a 56% increase in median lifespan and a 30% increase in maximum lifespan. Males are also significantly longer-lived, though to a smaller degree and maximum lifespan is not extended. Heterozygous mutants of both sexes show an intermediate longevity. Lifespan of homozygous Orco null mutants is further increased by DR, but the relative increase in median and mean longevity is significantly greater when mutants were maintained in well-fed conditions [17272684].
| Fruit fly |
| rb | ruby | Loss-of-function mutation reduces mean lifespan by 33% and maximum lifespan by 22% [17435236]. | Fruit fly |
| esc | extra sexcombs | Males heterozygous for the null esc4 or the dominant negative esc9 mutation that are progeny of an out-cross to a O-R wild-type strain have median lifespan that is, respectively, 47% and 60% longer than the O-R control. When derived from an out-cross to a longer-lived C-S wild-type strain, heterozygous esc9 flies have a median lifespan that is 43% longer than the C-S control [20018689]. | Fruit fly |
| 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 |
| MTF-1 | Metal response element-binding Transcription Factor-1 | MTF-1 overexpression in either the peripheral nervous system or motorneurons extends both mean and maximum lifespan by 40% in males [18775584]. | Fruit fly |
| EcR | Ecdysone receptor | Mutant heterozygotes in EcR live on mean 40%-50% longer than controls [12610309; reviewed in 12610294]. Homozygous mutants in EcR are inviable. The developmental time and weight of EcR+/- mutants is the same as control, but resistance to temperature, oxidative stress, and starvation is increased in heterozygotes [12610309]. | Fruit fly |
| sdhC | succinate dehydrogenase, cytochrome b556 subunit | Mutants expressing a dominant negative form of sdhC in the nervous system have a 22% reduced mean lifespan and signs of oxidative stress induction [17854771]. | 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 |
| mys | myospheroid | mys mutants exhibit ameliorated age-related declines in locomotor activity and an increase in mean lifespan of 20% [14570233]. | Fruit fly |
| Naam | Nicotinamide amidase | Naam overexpression increases mean and maximum lifespan by 30% in both females and males. The lifespan extension is reversed by Sir2 mutants, indicating the it is dependent on Sir2 [18678867]. | 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 |
| 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 |
| DNApol-gamma35 | DNA polymerase gamma 35kD | Overexpression of DNApol-gamma35 (DNA polymerase gamma) in the nervous system results in a decrease in the median lifespan ranging from 39% to 52% [17999718].
| Fruit fly |
| Ef1alpha48D | Elongation factor 1alpha48D | Overexpression of Ef1alpha48D (transformed with a P-element vector and under control of hsp70 regulatory sequences) results in lifespan extension by 18-41%. The decrease in protein synthesis that accompanies aging is preceded by a decrease in EF-1 alpha protein and mRNA [2508089]. | Fruit fly |
| Eip71CD | Ecdysone-induced protein 28/29kD | Overexpression of Eip71CD (alias MsrA) in nervous system extends the lifespan by up to 70%, increased resistance to oxidative stress, and delays the onset of senescence-induced decline in activity levels and reproductive capacity. Eip71CD is a downstream effector of foxo [22310715].
Mean and maximum lifespan is increased by up to 2-% in animals that overexpress Eip71CD [20655917]. | Fruit fly |
| fh | frataxin homolog | Overexpression of fh in the mitochondria of female transgenic animals increases antioxidant capability, resistance to oxidative stress insults, and longevity [18258192]. | Fruit fly |
| Gclc | Glutamate-cysteine ligase catalytic subunit | Overexpression of Gclc extends mean and maximum lifespan by up to 50% [16148000]. | Fruit fly |
| Gclm | Glutamate-cysteine ligase modifier subunit | Overexpression of Gclm extends the mean lifespan by up to 24% [16148000]. | Fruit fly |
| Hsc70-3 | Heat shock protein cognate 3 | Overexpression of Hsc70-3 increases average female lifespan by 27% [18059160]. | Fruit fly |
| Hsp26 | Heat shock protein 26 | Overexpression of Hsp26 (by the UAS/GAL4 system) increases stress resistance and extends the mean lifespan by 30% [15308776]. | Fruit fly |
| Hsp27 | Heat shock protein 27 | Overexpression of Hsp27 (by the UAS/GAL4 system) increases stress resistance and extends the mean lifespan by 30% [15308776]. | 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 |
