aak-2 | AMP-Activated Kinase 2 | AAK-2 could be a sensor that couples energy levels and insulin-like signals to lifespan. aak-2(ok524) knockout mutants have a 12% and 18% shorter mean and maximum lifespan, respectively as well as faster age-dependent accumulation of a lipofuscin-like fluorescent pigment in the intestine [15574588]. sDR increases AMP:ATP ratio. aak-2 mutation suppresses lifespan extension and delay of the decline in locomotor activity resulting from sDR. A constitutive active mutation of aak-2 is sufficient to cause increase stress resistance as well as to significantly extend lifespan. Both increased stress resistance and extended lifespan is reverted in daf-16 knockdown by RNAi. sod-3 mRNA is increased by constitutive active form of aak-2 and decreased by aak-2 mutation. The increase in sod-3 mRNA is dependent on expression of DAF-16. Worm and human AMPK phosphorylate DAF-16 (greatly enhanced by presence of AMP) at least in six residues (T166, S202, S314, S321, T463 and S466) [17900900]. aak-2 mutation cancels out the lifespan extension effect of sDR and PD, regardless of the concentration of bacteria or peptones. bDR significantly extends lifespan of aak-2 mutants, but to lesser extent than that of wild-type. eat-2 mutation extends the lifespan of aak-2 mutants to the same extent than that of wild-type. Resveratrol does not increase lifespan of aak-2 mutants [19239417]. daf-2(m577);aak-2(ok524) double mutant has a lifespan that is indistinguishable from those of aak-2(ok524) single mutant. Transgenic animals with a higher aak-2 gene dose live on average 13% longer with a maximum lifespan extension on up to 25% [15574588]. | Nematode |
aakb-1 | AMP-Activated Kinase Beta subunit 1 | RNA interference of aakb-1 results in decreased lifespan and earlier accumulation of lipofuscin [16673436]. | Nematode |
aakb-2 | AMP-Activated Kinase Beta subunit 2 | RNA interference of aakb-2 results in decreased lifespan and earlier accumulation of lipofuscin [16673436]. | Nematode |
aakg-2 | AMP-Activated protein Kinase Gamma subunit 2 | aakg-2 overexpression extends mean, median, and maximum lifespan by 47, 45, and 35%. Overexpression of aakg-2 toegther with D. rerio ucp2 was non-additive with sDR [22737090]. | Nematode |
AAT1 | Aspartate AminoTransferase 1 | Overexpression of AAT1 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction [18381895]. | Budding yeast |
abu-11 | Activated in Blocked Unfolded protein response 11 | Overexpression of abu-11 extends mean lifespan by 9% to 28% [16256736]. | Nematode |
ACH1 | Acetyl CoA Hydrolase 1 | ACH1 deletion cells accumulate a high amount of extracellular acetic acid and display a reduced mean and maximum chronological lifespan. Maximum lifespan is reduced by 32%. Lifespan shortening is completely abrogated by alleviating the acid stress either by a DR regimen that prevents acetic acid production or by transferring chronologically aging mutant cells to water. Deletion of ACH1 is accompanied by reactive oxygen species accumulation, severe mitochondrial damage, and an early insurgence of apoptosis [22754872]. | Budding yeast |
ACO1 | ACOnitase 1 | Deletion of ACO1 decreases mean chronological lifespan by 42 - 56% in diploid cells [21447998]. | Budding yeast |
AFG3 | ATPase Family Gene 3 | Deletion of the mitochondrial AAA protease AFG3 increases replicative lifespan by 20% in the alpha and a strains [18340043], but decreases chronological lifespan by 37 - 51% in diploid cells [21447998].
AFG3 deletion changes mean, median and maximum lifespan by 15 to 26% 17 to 30% and -25 to +58%, respectively.
AFG3 deletion leads to reduced cytoplasmic mRNA translation and its lifespan extension is independent of Sir2 and Hac1, but requires Gcn4. AFG3 deletion further extends the lifespan of cell deficient in both SIR2 and FOB1, but fails to extend the lifespan of dietary restricted cells or cells lacking GCN4. Gcn4 protein levels are increased in afg3 mutants. The deletion of AFG3 fails to extend the replicative lifespan in the W303AR strain. AFG3 deletion does deletion extend the replicative lifespan at 15°C. | Budding yeast |
agmo-1 | AlkylGlycerol MonoOxygenase 1 | RNA interference of agmo-1 decreases median lifespan by 30% in wild type animals and 60% in daf-2 mutants [18006689]. | Nematode |
ain-1 | ALG-1 INteracting protein 1 | RNA interference of ain-1 decreases median lifespan by 10% in wild type animals, 20% in a daf-2 background and 44% in daf-2/daf-16 double mutants [18006689]. | Nematode |
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 |
AKR1 | AnKyrin Repeat-containing protein 1 | Deletion of AKR1 decreases replicative lifespan by 40% in the alpha strain [18340043]. Replicative lifespan decreased by 50% in the alpha strain [19030232]. | Budding yeast |
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 |
alg-1 | Argonaute (plant)-Like Gene | Adult-specific knockdown of the C. elegans argonaute-like gene 1 alg-1 results in shortened lifespan with a reduction in the mean and maximum lifespan by 9 - 16% and 14%, respectively [21810936]. | Nematode |
alg-2 | Argonaute (plant)-Like Gene 2 | RNA interference of alg-2 decreases median lifespan by 24% in wild type animals and 50% in a daf-2 background [18006689]. | Nematode |
ANS1 | — | Deletion of ANS1 decreases replicative lifespan by 25% in the alpha strain [19030232]. | Budding yeast |
aqp-1 | AQuaPorin or aquaglyceroporin related 1 | aqp-1 expression changes in response to glucose or glycerol. Similar to daf-16 and hsf-1 mutants, aqp-1 mutants were short-lived, and their short lifespan was not further decreased by glucose. Overexpression of aqp-1::GFP rescues short lifespan of aqp-1 deletion mutants and partially prevented glucose from shortening lifespan. Glucose or glycerol feeding downregulates aqp-1 in wild-type. In daf-16 and/or hsf-1 mutants aqp-1 is repressed and glucose feeding does not significantly affect its expression. aqp-1 mutation does not further decrease the short lifespan of daf-16 and/or hsf-1 mutants. aqp-1 transgene is expressed in pharynx and intestine (which behaves as entire endoderm of animal, including adipose tissues). Dietary glucose does not cause significant differences in levels of glucose or glycerol in wild-type vs. aqp-1 mutants [19883616]. | Nematode |
Arhgap1 | Rho GTPase activating protein 1 | Most Ahrgap1 knockout mice are weak and die during the neonatal period. Animals that survived have a shorter lifespan (median lifespan is 12 months) and show premature aging-like phenotypes, including a reduction in body mass, a loss of subdermal adipose tissue, lordokyphosis, and osteoporosis [17227869]. | House mouse |
arl-8 | ARF-Like 8 | RNA interference of arl-8 decreases median lifespan by 35% in a daf-2 background and 9% in daf-2/daf-16 double mutants [18006689]. | Nematode |
Arntl | aryl hydrocarbon receptor nuclear translocator-like | Arntl knockout mice display symptoms of premature aging including a shorter lifespan, sarcopenia, cataracts, less subcutaneous fat, and organ shrinkage [16847346]. | House mouse |
ARP1 | Actin-Related Protein 1 | Deletion of ARP1 decreases replicative lifespan by 40% in the alpha strain [18340043; 19030232]. | Budding yeast |
arx-4 | ARp2/3 compleX component 4 | RNA interference of arx-4 decreases median lifespan by 61% in a daf-2 background and 51% in daf-2/daf-16 double mutants [18006689]. | Nematode |
ATG1 | AuTophaGy related 11 | ATG1 deletion reduces chronological lifespan by 70% [19302372]. Deletion of ATG1 reduces replicative lifespan by 20% in the alpha strain [18340043]. | Budding yeast |
ATG16 | AuTophaGy related 16 | Under AL atg16 mutation shortens chronological, but not replicative lifespan. 0.5% glucose DR extends chronological lifespan of atg16 mutants, but amino-acid DR does not extend the short chronological lifespan of atg16 mutants (similar to several other autophagy mutants). ADE4 deletion in atg16 mutants results only in a partial extension of chronological lifespan by 0.5% glucose DR. The long chronological lifespan of tor1 mutants requires ATG16 [20421943]. | Budding yeast |