| cher | cheerio | Overexpression of cher from a doxycycline-inducible promoter results in a 7 - 9% increase in mean lifespan (in PdL x rtTA; Oregon-R x rtTA) [12620118]. | Fruit fly |
| Mt2 | DNA methyltransferase 2 | Overexpression of Dnmt2 extends mean and maximum lifespan [15533947]. | 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 |
| fabp | fatty acid bindin protein | Overexpression of fabp (CG6783) throughout the whole body increases mean, median and maximum lifespan by 77, 81 and 13%, increases stress resistant (to paraquat but not starvation), consistently reduces mortality rate across adult ages and reduces the lifespan extension of DR by 12% [22997544].
fabp overexpression increases the dFOXO nuclear localization in the fat-body. mRNA levels of dFOXO target genes l(2)efl and 4E-BP in the adult whole bodies increases in response to overexpression of fabp [22997544].
Females of the genotype Act-GS-Gal4 > UAS-CG6783 exhibit an increase in median lifespan compared to uninduced control in response to feeding with RU486-containing food from day 3 of adulthood (P < 0.0001). Mean lifespan is extended by 10, while maximum lifespan is decreased by 11% [22997544]. | 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 |
| Fwd | four wheel drive | Overexpression of Fwd (from a doxycline-inducible promoter) increases mean lifespan by 7-9% [12620118]. Fwd regulates actin organization and ring canal formation during germline cytokinesis [10934029] by catalysing the first step in the synthesis of the key regulatory membrane phsopholipid PIP2, which is generated from PIP by a PI 4,5-kinase. | 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 |
| gig | gigas | Overexpression of gig, also known as dTsc2, results in lifespan extension. Overexpression of dTsc2 increases mean lifespan by 20% and 12%, at 25°C and 29°C, respectively, and protects from deleterious effects of rich food, as if mimicking the effect of DR [15186745].
Overexpression of dTsc2 via a UAS promoter in the eye using the driver gmr-GAL4 or in the nervous system by using appI-GAL4 does not extend the lifespan. Using the drivers 24BGAL4 and PO188-GAL4, enhancer traps that are predominantly expressed in the muscle and fat results in mean lifespan extension of 27% and 37%, respectively, at 29°C [15186745]. Fat-specific drivers DJ634-GAL4 and PO163-GAL4 when used to overexpress dTsc2, also led to a mean lifespan extension of 22% and 31%, respectively, at 29°C [15186745]. | Fruit fly |
| GLaz | Glial Lazarillo | Overexpression of GLaz results in increased resistance to hyperoxia (100% O2) and a 29% extension of mean lifespan under normoxia. Lifespan was also extended 30-60% under starvation [16581512]. Loss-of-function mutation of GLaz which decreases its expression of GLaz results in shorter lifespan and decreased resistance to oxidative stress in males [16581513]. | Fruit fly |
| hep | hemipterous | Overexpression of hey significantly extends median (50%) and maximum (25%) lifespan. A hypomorphic allele of hep (hep1) laerlgy prevents lifespan extension caused by puc heterozygosity [14602080]. | Fruit fly |
| Hsc70-3 | Heat shock protein cognate 3 | Overexpression of Hsc70-3 increases average female lifespan by 27% [18059160]. | Fruit fly |
| Hsp23 | Heat shock protein 23 | Overexpression of Hsp23 increases mean lifespan by more than 30% and increases the premortality phase [14734639]. | 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 |
| 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 |
| 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 |
| PGRP-LF | Peptidoglycan recognition protein LF | Overexpression of PGRP-LF increases mean and maximum lifespan by 13% and 24% [22366109]. | Fruit fly |
| Pink1 | PTEN-induced putative kinase 1 | Overexpression of Pink1 and overexpression of Pink1 with alpha-synclein results in an increase in lifespan which is accompanied by an increase in healthspan (as measured by mobility) when driven by a dopaminergic cells targeting TH-Gla4 transgene [22653599]. | 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 |
| SIFR | SIFamide receptor | Overexpression of SIFR in males extends mean and maximum lifespan by 23% and 3%, respectively [22366109]. | Fruit fly |
| Sin3A | — | Overexpression of Sin3A increases mean and maximum lifespan by 13% and 3%, respectively [22366109]. | 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 |
