| S6k | RPS6-p70-protein kinase | Ubiquitous overexpression of a dominant-negative form of S6k (alias dS6K) increases mean lifespan by 22% and overexpression of a constitutively active form of S6k decreases mean lifespan by 34% at 29°C. Overexpression of a dominant-negative form of S6k protects mutants from deleterious effects of rich food, as if mimicking the effect of DR [15186745]. | Fruit fly |
| Edem1 | — | The mean lifespan of Edem1 mutants of both male and female is increased by more than 30% [19302370]. | Fruit fly |
| ovo | — | The dominant ovoD1 allele extends female lifespan by approximately 50%. It does not synergize or prevent life-extension caused by chico [10617470; 11292874].
ovoD1 mutants are sterile [Mevel-Ninio et al. 1991]. | 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 |
| sun | Stunted | sun mutations increases lifespan and resistance to oxidative stress [15133470] | 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| p53 | — | Overexpression of wild-type p53 during adult life has no significant effect on lifespan. Expression of dominant-negative versions of p53 in adult neurons extends lifespan by 58% in females and by 32% in males and increases resistance to genotoxic stress and resistance to oxidative stress, but not to starvation or heat stress, while not affecting egg production or physical activity.
Dominant negative p53 expression cancels out lifespan extension effect of DR, low calorie-food (5% SY). Muscle or fat body specific expression of a dominant negative form of p53 as well as globally lack of p53 decreases lifespan [16303568]. Loss of p53 activity slightly shortens the lifespan. Mutants that lack p53 survive well up to 50 days, but mortality rate increases relative to wild-type at later ages. p53 mutant animals are extremely sensitive to irradiation [12935877].
Expression of dominant-negative (DN) form of p53 in adult neurons, but not in muscle or fat body cells, extends median lifespan by 19% and maximum lifespan by 8%. The lifespan of dietary-restricted flies is not further extended by simultaneously expressing DN-DMp53 in the nervous system, indicating that a decrease in Dmp53 activity may be part of the DR lifespan-extending effect. Selective expression of DN-Dmp53 in only the 14 insulin-producing cell (IPCs) in the brain extends lifespan to the same extent as expression in all neurons and this lifespan extension is not additive with DR [17686972].
| Fruit fly |
| InR | Insulin-like 1 receptor | Mutations in InR (InRE19/InRp5545 transheterozygous) result in dwarf females with extended lifespan of up to 85% and dwarf males with reduced late age-specific mortality (although no significant change in lifespan) [11292875]. InrGC25/InrE19 transheterozygous animals are short-lived an exhibit an elevated rate of age-independent mortality [11292874].
Natural allelic variation in InR are associated with variation in lifespan [15013662; 20074316]. | Fruit fly |
| pex1 | peroxin 1 | Mutation of the promoter region of pex1(S4868), results in lower expression levels and increases lifespan in males and females by 16% and 13%, respectively. pex1 mutation increases mean and maximum lifespan and males/females by 27-23/14-19% and 0-15%, respectively [22509016]. | Fruit fly |
| pex13 | peroxin 13 | Mutation of pex13(KG04339), located in its promoter region, results in lower gene expression and increased lifespan by around 16% and 13% in males and females. pex13 mutation increases mean and maximum lifespan by 23-27/14-19% and 11%, respectively [22509016]. | Fruit fly |
| snz | snazarus | Mutation in snz increases maximum lifespan of both sexes by up to 66%, while the median female lifespan is approximately 85% higher and that of males around 72% [18478054]. | Fruit fly |
| egm | enigma | Mutation in egm confers resistance to oxidative stress and extends the lifespan [16434470]. | Fruit fly |
| chico | Insulin receptor substrate-1 | Mutation in chico extends mean, median, and maximum lifespan by 56%, 48%, and 42% in homozygotes and 44%, 36%, and 35% in heterozygotes. chico mutation produces dwarf, long-lived females at normal nutrition. Male heterozygous live 13% longer than wild-type, but male homozygous have a shortened lifespan [11292874]. Wild-type and chico mutant females have similar peak lifespan under DR, but the food concentration at which these are achieved is shifted to higher amounts. chico mutation induces a state equivalent to submaximal, DR-induced slowing of aging [11951037]. chico heterzoygous females have a reduced fecundity and homozygous recessive mutants are sterile. chico heterozygous mutants are resistant to starvation but not oxidative stress or temperature stress [11292874]. | Fruit fly |
| mth | methuselah | Mutants in mth display approximately 35% and 36% increase in average and maximum lifespan as well as enhanced resistance to various forms of stress (including starvation, high temperature, and dietary paraquat) [9794765].
Reduced expression of mth targeted only to the insulin-producing cells of the brain is sufficient to extend lifespan and to enhance oxdative stress resistance [23121290].
IPC-targeted overexpression of β-arrestin alone mimics the longevity phenotype of reduced mth signaling [23121290]. | Fruit fly |
| EcR | Ecdysone receptor | Mutant heterozygotes in EcR live on mean 40%-50% longer than controls [12610309; reviewed in 12610294]. Homozygous mutants in EcR are inviable. The developmental time and weight of EcR+/- mutants is the same as control, but resistance to temperature, oxidative stress, and starvation is increased in heterozygotes [12610309]. | Fruit fly |
| esc | extra sexcombs | Males heterozygous for the null esc4 or the dominant negative esc9 mutation that are progeny of an out-cross to a O-R wild-type strain have median lifespan that is, respectively, 47% and 60% longer than the O-R control. When derived from an out-cross to a longer-lived C-S wild-type strain, heterozygous esc9 flies have a median lifespan that is 43% longer than the C-S control [20018689]. | Fruit fly |
| Rpd3 | Histone deacetylase Rpd3 | Males heterozygous for hypomorphic (partial loss-of-function) or null mutation of Rpd3 have a lifespan extension of 33% and 41 - 47%, respectively. Females heterozygous for a hypomorphic allele have a 52% increase in lifespan, but females carrying a null mutation have only modest increase in maximum lifespan (but not median lifespan). Longevity increases to the same extent in wild-type under low-calorie diet and rpd3 mutants fed normal diet. DR fails to further increase lifespan of rpd3 mutants. DR leads to a moderate but significant down-regulation of Rpd3, analogous to decrease obtained in heterozygotes carrying rpd3 mutation. rpd3 mutants fed normal food and wild-type fed low-calorie increase Sir2 expression two-fold [12459580]. | Fruit fly |
| Orco | Odorant receptor co-receptor | Loss-of-function mutation in Orco (alias Or83b) results in olfactory defects, altered adult metabolism, enhanced stress resistance, and life-extension. Fully fed female homozygous Or83b null mutants exhibit a 56% increase in median lifespan and a 30% increase in maximum lifespan. Males are also significantly longer-lived, though to a smaller degree and maximum lifespan is not extended. Heterozygous mutants of both sexes show an intermediate longevity. Lifespan of homozygous Orco null mutants is further increased by DR, but the relative increase in median and mean longevity is significantly greater when mutants were maintained in well-fed conditions [17272684].
| 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 |
| bchs | blue cheese | Loss of function mutation in bchs results in a 40-45% decrease in mean lifespan and is associated with age-related neurodegenerative phenotype with reduced CNS size and altered morphology as well as accumulation of insoluble ubiquinated proteins and amyloid precursor-like proteins along with an increase in neuronal apoptosis. No pronounced developmental defects were observed and young adults have normal behaviours, indicating that the bchs gene is essential for normal adult survival and longevity [12598614].
bchs mutation reduces mean lifespan by 28 - 54% and maximum lifespan by 24 - 46% [17435236].
Alfy (autophagy-linked FYVE protein) is the conserved human bchs homolog [15292400]. | 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 |
