| 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 |
| Gr63a | Gustatory receptor 63a | Gr63a loss-of-function in female flies leads to 30% extended mean lifespan, increased fat deposition, and enhanced resistance to some (but not all) environmental stresses. Lifespan of males is not extended [20422037].
Overexpression of Gr63a has modest negative effect on lifespan [20422037]. | Fruit fly |
| GstS1 | Glutathione S transferase S1 | GstS1 overexpression increases the mean lifespan by 33% [18059160]. | Fruit fly |
| hebe | — | Adult-specific overexpression of hebe increases the lifespan by 5-30% and modulates late-age female fecundity. Female and male mean lifespan is up to 11% and 24% higher [19011900]. | Fruit fly |
| Hsc70-3 | Heat shock protein cognate 3 | Overexpression of Hsc70-3 increases average female lifespan by 27% [18059160]. | Fruit fly |
| Hsp22 | Heat shock protein 22 | Overexpression of mitochondrial Hsp22 in all cells or specifically in motorneurons (using GAL4/UAS binary system) increases life lifespan by 32% and resistance to oxidative stress [19948727; 20036725].
Ubiquitous or a targeted expression of Hsp22 within motorneurons increases the mean lifespan by more than 30%. Hsp22 shows beneficial effects on early-aging events since the premortality phase displays the same increase as the mean lifespan [14734639].
Animals that do not express Hsp22 (due to a transposition into its transcriptional starting site) have a 40% decrease in lifespan, exhibit a 30% decrease in locomotor activity and are sensitive to mild stress [20036725].
Doxycyline-regulated overexpression of Hsp22 makes animals more sensitive to heat and oxidative stress as well as reduces the mean lifespan by up to 21%, particularly at higher culture temperature [15491684].
Hsp22-promoter driven reporter overexpression reduces mean and maximum lifespan [19420297].
Histone deacetylase inhibitor Trichostatin A (TSA) extends the lifespan of *Drosophila melanogaster* by promoting the hsp22 gene transcription, and affecting the chromatin morphology at the locus of hsp22 gene along the polytene chromosome [15346199].
| 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 |
| Hsp70Ba | Heat-shock-protein-70Ba | Hsp70Ba overexpression reduces mean and maximum lifespan up to 30% [19420297].
hsp70 and hsp22 RNA levels are higher in long-lived than in short-lived fly lines. The HDAC inhibitor TSA causes a higher expression of hsp22 and hsp70, and strikingly influences the lifespan in both long and short-lived lines, with variable degrees (up to 25%) [15695762]. | Fruit fly |
| Ilp2 | Insulin-like peptide 2 | Flies with an ablation of median neurosecretary cells (which eliminates Ilp2 expression) exhibit a significant increase in mean and maximum lifespan over that of control flies and an increase to oxidative stress and starvation. The mutants also exhibit increased storage of lipid and carbohydrate, reduced fecundity, and reduced tolerance of heat and cold [15708981]. The median and maximum lifespan of females is increased by 33.5% and 40%, respectively. In males the median and maximum lifespan is increased by 10.5% and 27%, respectively [15708981].
Ilp2 RNA interference results in a 24% to 47% increase in median lifespan [19005568].
Ilp2 is transcriptional down-regulated in long-lived mutants. Ilp2 null mutants are significant longer-lived with a 8-13% longer median lifespan, but have a normal DR response. Ilp2 Ilp3 Ilp5 triple null mutants fail to have a normal response to DR. Their response is right shifted, with mutants shorter-lived compared to wild-type on low but longer-lived on high yeast concentrations [20195512]. | 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 |
| kermit | — | The disruption of kermit (alias dGIPC) function results in premature loss of locomotor activity and reduced mean lifespan [21029723]. | Fruit fly |
| kuk | kugelkern | Overexpression of kugelkern in the adult muscle results in a 60% reduction of mean lifespan [18494863]. | Fruit fly |
| l(3)neo18 | lethal (3) neo18 | RNA interference of l(3)neo18 in females increases mean lifespan by 14-18% when applied during development and adulthood in the whole organism and by 8-24% when applied in the neurons. The effect is more variable in males. A consistent increase (8-18%) is however observed for whole organisms RNAi in adults [19747824].
l(3)neo18 (alias CG9762) is translational upregulated upon DR. Under rich nutritional conditions lifespan of l(3)neo18 RNAi knockout animals is indistinguishable from wild-type, while upon DR, lifespan extension is diminished in males and females [19804760].
| Fruit fly |
| LBR | Lamin B receptor | Overexpression of Lamin B receptor in the adult muscle and in the abdominal fat body results in a 54% and 46% reduction of mean lifespan, respectively [18494863]. | 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 |
| Loco | locomotion defects | Reduced expression of Loco due to hetero-deficient results in a 17-20% longer mean lifespan for both male and females, besides the fact that the homozygous deficiency of loco is lethal. Several of these long-lived mutants are more resistant to stresses such as starvation, oxidation and heat. Additionally, mutants have higher Manganese-containing superoxide dismutase (MnSOD) activity, increased fat content an diminished cAMP levels. Loco's RGS domain is required for the regulation of longevity as deletion analysis suggest [21776417]. | Fruit fly |
| magu | — | Adult-specific overexpression of magu increases lifespan by 5-30% and modulates late-age fecundity [19011900]. | 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 |
| 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 |
| Mnt | CG13316-PC, isoform C | A dMnt null allele results in flies with larger cells, increased weight, and decreased lifespan [16055719]. | 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 |
| mys | myospheroid | mys mutants exhibit ameliorated age-related declines in locomotor activity and an increase in mean lifespan of 20% [14570233]. | Fruit fly |
