| 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 |
| 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 |
| 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 |
| 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 |
| Hsp70Bb | Hsp70Bb 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 |
| Sin3A | — | Overexpression of Sin3A increases mean and maximum lifespan by 13% and 3%, respectively [22366109]. | 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 |
| CG30427 | — | Overexpression of CG30427 in males increases mean lifespan by 18% [22366109]. | Fruit fly |
| PGRP-LF | Peptidoglycan recognition protein LF | Overexpression of PGRP-LF increases mean and maximum lifespan by 13% and 24% [22366109]. | 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 |
| 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 |
| Hsp23 | Heat shock protein 23 | Overexpression of Hsp23 increases mean lifespan by more than 30% and increases the premortality phase [14734639]. | Fruit fly |
| CG10383 | — | Overexpression of CG10383 in males increases mean and maximum lifespan by 12% and 8%, respectively [22366109]. | Fruit fly |
| Akh | Adipokinetic hormone | Knockdown of the adipokinetic hormone (Akh) by RNAi (with an RU486-inducible and ubiquitously expressing Actin 5C-GS Gal4 strain) does not by itself affect lifespan, but significantly inhibits DR-dependent increase in lifespan across a range of yeast concentrations in both females and males. While control females and males exhibit a 113%/22% increase in lifespan under DR, upon Akh inhibition there was a significant reduction in lifespan extension with DR (52%/5%). Global Akh knockdown reduces starvation resistance by 24% upon DR, but no significant change upon AL. Also Akh RNAi repressed the DR-dependent increase in cold-stress resistance. Fat body and neuronal-specific inhibition of Akh by using RU486-inducible S(1)106-GS-Gal4 and Elav-GS-Gal4 enhancer traps, respectively, does not reduce lifespan extension upon DR. But, muscle-specific inhibition of Akh using RU486-inducible muscle enhancer trap (Mhc-GS-Gal4) reduces the DR-dependent increase in lifespan. While control exhibit a 47.2% lifespan extension, animals with muscle-specific Akh inhibition fails to result in any increase upon DR (i.e. completely blocked the DR lifespan extension). Muscle-specific Akh inhibition diminishes the increase in triglyceride synthesis and breakdown present normally under DR. A significant reduction in lifespan extension also occurs with a noninducible muscle driver (Mhc-Gal4). Controls on DR exhibit significant higher levels of spontaneous activity compared to Akh RNAi-inhibited animals at all ages. Akh inhibition reduces the protective effect of DR on age-related decline in muscle function/activity [22768842].
Fat-body specific Akh RNAi results in increased spontaneous activity and a small but significant increase in lifespan upon AL [22768842].
Overexpression of Akh in a ubiquitousness manner enhances fat metabolism (significant increase in triglyceride synthesis and breakdown under AL), spontaneous activity (148% on AL and 154% on DR), and lifespan on AL (33%). However, despite and increase in movement under DR, lifespan is not increased under a restricted diet [22768842]. | Fruit fly |
| SIFR | SIFamide receptor | Overexpression of SIFR in males extends mean and maximum lifespan by 23% and 3%, respectively [22366109]. | 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 |
| sm | smooth | Overexpression of sm in males increases mean and maximum lifespan by 29% and and 16%, respectively [22366109]. | Fruit fly |
| CG10916 | Mediator complex subunit 9 | Overexpression of CG10916 in males increases mean and maximum lifespan by 27% and 26%, respectively [22366109]. | Fruit fly |
| Atg8a | Autophagy-related 8a | Mutations in Atg8a results in reduced lifespan and increased sensitivity to oxidative stress while enhanced expression in older fly brains extends average adult lifespan by 56% and promotes resistance to oxidative stress [18059160].
Atg8a mutation reduces the maximum lifespan by 25% under starvation conditions [17617737].
Loss-of-function mutation in Atg8a reduces mean lifespan by 11 - 25% and maximum lifespan by 3 - 22% [17435236]. | Fruit fly |
| 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 |
| 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 |
| CG13890 | — | Overexpression of CG13890 (DCI) throughout the whole body increases mean and median lifespan by 35 and 31%, but decreases maximum lifespan by 6%, increases stress resistant (to paraquat and starvation), consistently reduces the mortality rate across adult ages and reduces the lifespan extension of DR by 15% [22997544].
CG6783 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 CG6783 [22997544]. | Fruit fly |
| Cct1 | CTP:phosphocholine cytidylyltransferase 1 | Overexpression of Cct1 from a doxycycline-inducible promoter results in a 6 - 8% increase in mean lifespan (in the PdL x rtTA; Oregon-R x rtTA strain) [12620118].
Cct1 exhibits a non-coding region difference unique to animals under experimental evolution selected for longevity and is upregulated in head of animals that were selected for longevity at all ages beyond the day of eclosion [23106705]. | Fruit fly |
