| 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 |
| Sirt2 | — | Decreased expression of Sirt2 by RNA interference causes lethality during development. Silencing in neurons shortened mean lifespan by 20% [17159295]. | Fruit fly |
| Sirt6 | — | Decreased expression of Sirt6 by RNA interference causes lethality during development. Sirt6 silencing in neurons shortens mean lifespan by 20% [17159295]. | Fruit fly |
| Sod1 | Superoxide dismutase | Simultaneous overexpression of catalase and Sod (alias Sod1) results in a one-third lifespan extension, a slower rate of mortality acceleration, and a delayed loss in physical performance, but neither has any effect on lifespan alone [8108730]. General overexpression of Sod (also known as Cu/ZnSOD) alone is sufficient to extend lifespan by up to 48%. Simultaneous overexpression of catalase with Cu/ZnSOD has no added benefit, presumably due to a pre-existing excess of catalase [9858546]. Sod1 reduction by knockdown or knockout blunts the lifespan extension by a high sugar-low protein diet, but not a low-calorie diet [22672579].
Sod mutant flies display infertility and a reduction in lifespan [2539600]. | Fruit fly |
| Sod2 | Superoxide dismutase 2 (Mn) | RNA interference of Sod2 results in increased oxidative stress and early-onset mortality in young adults [12456885]. Overexpression of Sod2 by 5-115% decreases lifespan by 4-5% without any compensatory changes in metablic rate, level of physical activity, or the levels of other antioxidants (Sod, Cat, and glutathione) [10545213]. Targeted overexpression of Sod2 in motor neurons alone extends lifespan by 30% [11113599]. Induced overexpression of Sod2 in adult animals extends lifespan up to 37% [12072463]. Overexpression of catalase in combination with SOD2 has no added benefit for lifespan [12072463]. Animals overexpressing SOD2 or catalase do not exhibit a decrease in metabolism as measured by oxgen consumption [12072463].
Sod2 overexpression results in a 20% increase in mean and maximum lifespan [18067683]. | Fruit fly |
| sug | sugarbabe | Overexpression of sug (from a doxycycline-inducible promoter) results in a 5-9% increase in mean lifespan [12620118]. | Fruit fly |
| sun | Stunted | sun mutations increases lifespan and resistance to oxidative stress [15133470] | Fruit fly |
| Surf1 | surfeit gene 1 | Surf1 knockdown results in larval lethality. However, knockdown in the central nervous system (CNS) not only bypasses the larval lethality but it results in an increase in maximum lifespan of about 20-30% [16172499]. | Fruit fly |
| Trx-2 | thioredoxin-2 | Trx-2 mutants have a 25% reduction in maximum lifespan and exhibit lower tolerance to oxidative stress while animals carrying multiple copies of Trx-2 exhibit higher tolerance [17567437]. | Fruit fly |
| TrxT | Thioredoxin T | Overexpression of TrxT in neurons increases the level of locomotor activity in aged flies and extends the mean lifespan by 15% [17301052]. | Fruit fly |
| 14-3-3epsilon | CG31196 gene product from transcript CG31196-RA | Loss of 14-3-3ε results in increased stress-induced apoptosis, growth repression and extended lifespan of flies, in a foxo-dependent manner. Mean lifespan of males and females is increased by 25% and 49%, respectively. Increased 14-3-3ε expression also reverts foxo-induced growth defects. No effect of lifespan is observed when overexpressing 14-3-3ε in adipose tissue, indicating that endogenous foxo activity in this tissue is low under normal conditions [18665908]. | 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 |
| alpha-Man-I | alpha Mannosidase I | alpha-Man-I mutant fly exhibit enhanced resistance to paraquat and starvation an a 60% increase in mean lifespan for both sexes. After outcrossing, the mutant exhibit, under normal conditions, an increase in mean lifespan of 22% for females and 38% for males. Maximum lifespan is increased by 15%. alpha-Man-I RNAi knockdown results in a 39% increase in mean lifespan [19302370]. | Fruit fly |
| Atg2 | Autophagy-specific gene 2 | Atg2 overexpression increases average female lifespan by 28% [18059160]. | 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 |
| CG17856 | — | RNAi of CG17856 results in an increase in mean lifespan of 13-18% in females. In the case of males and post-developmental experiments the results are variable [19747824]. | Fruit fly |
| CG18809 | — | RNAi of CG18809 results in a 7-19% increase in mean lifespan of females, while neural RNAi results in an increased mean lifespan of up to 12% in females. For males the results are variable [19747824]. | Fruit fly |
| CG5389 | — | RNAi of complex V subunit CG5389 results in increased mean longevity under standard laboratory food conditions (3% yeast) in males. RNAi started from the development results in a mild lifespan increase in both sexes (3-11% in females and 3-8% in males). Post-developmental RNAi and silencing limited to neurons has variable effects with reduction in lifespan of up to 9% [19747824]. Under rich media conditions CG5389 knockdown throughout development and adulthood increases mean lifespan by 26% and abolished the lifespan extension by DR (started in the adulthood) in males. Suppression of CG5389 only during the adulthood either via RNAi by tub-GS or via oligomycin (a specific inhibitor of complex V) feeding prevents an increase in longevity under DR (started in the adulthood) in males [19968629]. | Fruit fly |
| CG9172 | — | RNAi against CG9172 increases mean lifespan in females by up to 4-12% when applied in both development and adulthood, and up to 46% when applied in adult neurons only. For males the effect is variable [19747824]. | 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 |
| 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 |
| E(z) | Enhancer of zeste | Flies heterozygous for the protein null E(z)63 or the catalytically inactive E(z)731 mutation that are progeny of an out-cross to an Oregon-R (O-R) wild-type strain exhibit a substantially greater median lifespan than the O-R control (71% and 76%, respectively). When derived from an out-cross to a longer-lived Canton-S (C-S) wild-type strain, the median lifespan of E(z)63 heterozygous is 33% longer than the C-S control [20018689]. | Fruit fly |
| Edem1 | — | The mean lifespan of Edem1 mutants of both male and female is increased by more than 30% [19302370]. | Fruit fly |
| elav | embryonic lethal abnormal vision | elav mutation significantly decreases the lifespan. Median lifespan in males is 66% lower [20589912]. | Fruit fly |
