| 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 |
| Akt1 | CG4006 gene product from transcript CG4006-RA | RNA interference of Akt1 in intestinal stem cells, results in impaired regeneration of the intestinal epithelium and a short lifespan. In males and females on mean lifespan is 11.4% and 7.4% lower [20976250]. | Fruit fly |
| Atg2 | Autophagy-specific gene 2 | Atg2 overexpression increases average female lifespan by 28% [18059160]. | Fruit fly |
| Atg7 | Autophagy-specific gene 7 | Knockouts of Atg7 are short-lived with a 30% reduction in maximum lifespan and are hypersensitive to nutrient and oxidative stress [18056421; 19550147]. | 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 |
| Aut1 | — | Aut1 depletion form the first day of imaginal stage shortens lifespan by 28% on average in Drosophila and causes morphological behavioural features of premature aging [18219227]. | Fruit fly |
| bam | bag of marbles | Bam mutants have an extended lifespan due to germ cell loss. Lifespan of females is on average up to 50% higher and that of males on average s up to 27.8% higher [18434551]. | Fruit fly |
| bsk | basket | RNA interference of bsk in intestinal stem cells, results in short lived mutants with impaired intestinal homeostasis and tissue regeneration. The mean lifespan of males is 16.4% lower and those of female is reduced by 10.2% [20976250]. | Fruit fly |
| car | carnation | Loss-of-function mutation in car results in reduction of mean lifespan by 34 - 63% and maximum lifespan by 28 - 29% [17435236]. | 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 |
| 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 |
| Cdk5 | Cyclin-dependent kinase 5 | Cdk5 loss-of-function mutations result in defective axon guidance, age-dependent behavioral deficits and reduced lifespan by about one third [17368005]. | Fruit fly |
| cert | ceramide transfer protein | cert mutants exhibit a shortened lifespan accompanied by enhanced oxidative damage to cellular proteins and metabolic compromise, such as increasing glucose levels, reminiscent of premature aging [17592126]. | Fruit fly |
| CG10383 | — | Overexpression of CG10383 in males increases mean and maximum lifespan by 12% and 8%, 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 |
| 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 |
| CG30427 | — | Overexpression of CG30427 in males increases mean lifespan by 18% [22366109]. | Fruit fly |
| CG3776 | — | Both overexpression and underexpression of CG3776 (alias Jhebp29) reduces the mean lifespan, where the reduction in males is slightly higher.
The lifespan of male flies with under- and overexpressed CG3776 is reduced by 38.8 and 42.6%, respectively when compared with Oregon R flies.The lifespan of female flies with under- and overexpressed CG3776 is reduced by 31.6 and 35%, respectively when compared to Oregon R flies.
Among the males and females, relatively to Oregon R and EP835/CyO, the age-specific survival of EP835/EP835 and EP835/Gal4 is reduced in both log-rank and Wilcoxon tests (P < 0.001); survival of EP835/EP835 and EP835/Gal4 differed using the log-rank-test (male: P<0.001; female: P=0.027) [18275960].
| 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 |
| cm | carmine | Loss-of-function mutation in cm reduces mean lifespan by 43 - 53% and maximum lifespan by 40 - 44% [17435236]. | Fruit fly |
| Dcr-2 | Dicer-2 | Median lifespan of homozyogous and transheterozyogous Dcr-2 mutants is reduced by 18-36% in males and by 27-36% in females. Dcr-2 loss changes the expression of mostly metabolic genes implicated in stress resistance and aging. Dcr-2 mutants are hypersensitive to oxidative, endoplasmic reticulum, starvation and cold stress as well as abnormal lipid and carbohydrate metabolism [21889502]. | Fruit fly |
| DJ-1alpha | DJ-1α | RNA interference of DJ-1alpha shortens maximum lifespan by 13% and results in increased sensitivity to oxidative stress and motor impairments [17651920]. | Fruit fly |
| dj-1beta | dj-1β | Loss of function mutation in dj-1beta shortens maximum lifespan by 40% and results in increased sensitivity to oxidative stress and motor impairments [17651920]. | Fruit fly |
| DLP | Daxx-like protein | DLP mutants have a 20% shorter mean lifespan and reduced female fertility [17933869]. | Fruit fly |
| dor | deep orange | Loss-of-function mutation in dor reduces mean lifespan by 70 - 81% and maximum lifespan by 71 - 78% [17435236]. | Fruit fly |
