| TSA1 | Thiol-Specific Antioxidant 1 | A gain-of-function allele of peroxiredoxin (thioredoxin peroxidase, Tsa1) causes a dominant oxidative stress-resistance and robust premature aging phenotype with reduced mean lifespan. These effect is not provoked by altered Tsa1 levels, nor can it be stimulated by deletion, haploinssufficiency or overexpression of wild-type allele [20729566]. Disruption of TSA1 shortens chronological lifespan [15129730]. Replicative lifespan extension by DR in sir2;fob1 double mutant is reduced by TSA1 deletion mutant. Wild-type cells require TSA1 to fully extend lifespan. Mutation in CDC35 (adenylate cyclase), a genetic mimetic of DR, is dependent on TSA1 to extend lifespan [21884982]. | Budding yeast |
| Hells | helicase, lymphoid specific | A hypomorphic deletion of helicase domains 3, 4 and part of 2, leads to expression of a C-terminal truncated Hells protein causing an extremely short lifespan. with 60% of homozyogous mutants dying after birth and remaining 40% surviving up to seven weeks (around 25 days) [15105378].
Hells disruption results in genomic hypomethylation, de-repression of silenced genes, and premature aging, characterized by decreased proliferation, increased replicative senescence, and altered expression of Bmi-1 and p16INK4a. Hells mutant exhibit significant hypoglycemia, low birth weight and growth retardation, and signs of premature aging such as greying hair and balding, reduced fat deposition, unstable gait, cachexia, and kyphosis [15105378]. | House mouse |
| lin-4 | abnormal cell LINeage 4 | A loss-of-function mutation in lin-4 shortens lifespan and accelerated tissue ageing while overexpressing lin-4 extends lifespan by redarding aging [16373574].
lin-4 is regulated by DAF-16 in L1 arrest. | Nematode |
| CKIepsilon | casein kinase I epsilon | A mutation called tau, if homozygous, shortens the circadian period (by 20%), increases metabolic rate (by 20%), and increases lifespan by 14-16% under conditions of constant darkness [12054192].
Male and female wild-type hamsters are heavier than homozygous mutants throughout the entire lifespan, and heterozygous mutants have intermediate weight [12054192]. | Syrian hamster |
| ATP2 | ATP synthase F1 subunit gamma | A temperature sensitive allele of ATP2 causes a clonal senescence phenotype resulting from the disruption of the age asymmetry between mother and daughter cells in that that daughter cells are born as old as they mother cells at 36 degree Celsius. This mutation of valine to isoleucine at amino acid 90 does not affect growth on non-fermentable carbon source. This allele is associated with loss of mitochondrial membrane potential as well as failure to segregate functional mitochondria to daughter cells [12242224]. | Budding yeast |
| 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 |
| 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 |
| Nlaz | Neural Lazarillo | Absence of Nlaz, which is homologous to ApoD, results in a reduced lifespan in both sexes. Median lifespan is 30.8% and 22.5% lower in females and males, respectively. Maximum lifespan is reduced by 12% and 30% in females and males [21376794]. | Fruit fly |
| 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 |
| 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 |
| hebe | — | Adult-specific overexpression of hebe increases the lifespan by 5-30% and modulates late-age female fecundity. Female and male mean lifespan is up to 11% and 24% higher [19011900]. | Fruit fly |
| magu | — | Adult-specific overexpression of magu increases lifespan by 5-30% and modulates late-age fecundity [19011900]. | Fruit fly |
| MSRA | methionine sulfoxide reductase A | Animals engineered to overexpress bovine MSRA in the nervous system have an extended median lifespan by up to 70% (relative to parental control), increased resistance to oxidative stress, and delayed the onset of senescence-induced decline in activity levels and reproductive capacity [11867705]. | — |
| 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 |
| 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 |
| 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 |
| ATG17 | AuTophaGy related 17 | ATG17 deletion decreases replicative lifespan under AL and blocks DR-lifespan extension. ATG17 mutant's replicative lifespan decreases by 70% on DR [18690010]. | Budding yeast |
| Atg2 | Autophagy-specific gene 2 | Atg2 overexpression increases average female lifespan by 28% [18059160]. | Fruit fly |
| ATG7 | Autophagy-related protein and dual specificity member of the E1 family of ubiquitin-activating enzymes; mediates the conjugation of Atg12p with Atg5p and Atg8p with phosphatidylethanolamine, required steps in autophagosome formation | ATG7 deletion reduces chronological lifespan by 70% [19302372]. | Budding yeast |
| Atm | Ataxia telangiectasia mutated homolog (human) | Atm-deficient mice are viable, retarded in growth, infertile (male produce no mature sperm and female no gametes), display neurological dysfunction, and exhibit severe defects in T cell maturation while going on to develop thymomas [8917548; 8689683]. The majority of mutant mice rapidly develop thymic lymphomas and die before 4 months of age [8843194].
Cells of Atm(-/-) mice exhibit slow growth also in culture and premature senescence, telomeres are extensively shortened in multiple tissues [8689683].
Mice mutant for Atm and Terc display progressive multi-organ system compromise and features of accelerated aging [12540856]. | House mouse |
| 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 |
| bar-1 | beta-catenin | BAR-1 may play a role in regulating daf-16 during dauer formation, particularly in conditions of oxidative stress as it directly interaction with DAF-16 and loss of bar-1 reduces activity of DAF-16 in dauer formation and lifespan. Deletion of bar-1 reduces mean (44%) and maximal (18%) lifespan, which is to a similar degree as seen to daf-16 mutants [15905404]. SMK-1 is important DAF-16 modulation of lifespan and specific stress response [5]. | Nematode |
| cbp-1 | CBP/p300 homolog 1 | bDR and daf-2 mutation induce cbp-1 expression. There is no decrease in cbp-1 expression in whole C. elegans during aging. Overexpression of cbp-1 does not significantly affect lifespan. daf-16 RNAi and cbp-1 RNAi reduce average lifespan under AL to about the same extent. Inhibiting cbp-1 via RNAi by 50%, specifically in adult phase and completely blocks lifespan extension of DD, bDR as well as eat-2, glp-1 and clk-1 mutation, but only partially that of daf-2 mutation and not at all that of cold. cbp-1 RNAi completely blocks the lifespan increase by daf-2 mutation under bDR. cbp-1 RNAi blocks the delay of other age-related pathologies by bDR. cbp-1 RNAi prevents protective effects of bDR and accelerates ABeta42-related pathology. bDR significantly delays onset of paralysis even in presence of cbp-1 RNAi. cbp-1 RNAi specifically in adults completely blocks lifespan extension by three distinct protocols of DR (mutation of eat-2), partly by daf-2 mutation but not of cold and blocks the delay of other age-related pathologies by bDR. cbp-1 RNAi has no effect on lifespan in daf-16 hypomorphic mutants. Combining cbp-1 and daf-16 RNAi in wild-type produces similar lifespan as either alone. Resistance to oxidative stress is strikingly reduced by cbp-1 RNAi and cbp-1 RNAi attenuates the protection against oxidative stress by bDR. cbp-1 RNAi accelerates accumulation of autofluorescence, but has no effect on activity, egg laying, or pharyngeal pumping. cbp-1 RNAi does not block induction of daf-16 or hsf-1 by bDR, but does block the induction of DAF-16 target gene, sod-3, and HSF-1 target gene, sip-1 by bDR. cbp-1 RNAi blocks induction of sod-3 expression by daf-2 RNAi. cbp-1 RNAi does not block the increased Nile Red staining produced by daf-2 mutation, but enhanced Nile Red staining. cbp-1 RNAi blocks the effect of bDR on metabolic gene expression from glycolysis towards beta-oxidation. Drugs that enhance histone acetylation increase lifespan and reduce ABeta42-related pathologies, but these protective effects are completely blocked by cbp-1 RNAi. cbp-1 RNAi decreases H4 Lys 5 acetylation and blocks the extension of lifespan as well as delays the onset of paralysis by ABeta1-42 transgene under AL and bDR by sodium butyrate (NaB) and trichostatin (TSA). cbp-1 RNAi does produce dye-filling defects in all C. elegans amphid neurons (ASI, ADL, ASK, AWB, ASH, and ASJ) [19924292]. | Nematode |
| bec-1 | BEClin (human autophagy) homolog 1 | bec-1 is required for normal dauer morphogenesis and lifespan extension. Knockdown of bec-1 via RNA interference results in a shortened mean and maximum lifespan by 14 and 5% [12958363]. bec-1 RNAi does not significantly change the lifespan of wild-type, but completely suppresses the longevity phenotype of eat-2 mutation [17912023; 18282106] and prevents lifespan extension by daf-2(e1370) mutation [12958363]. bec-1 RNAi causes the formation of abnormal dauers in a daf-2(e1379) background [12958363]. | Nematode |
