|mir-277 ||— ||Constitutive miR-277 expression shortens lifespan and synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype. Transgenic inhibition with a miRNA sponge construct also shortens lifespan .
miR-277 is downregulated during adult life .
mir-277 controls branched-chain amino acid catabolism and as a result it can modulate the activity of TOR kinase . ||Fruit fly |
|yata ||— ||yata mutation shortens the maximum lifespan by 68% and results in progressive deterioration of the nervous tissues and aberrant accumulation of Sec23 . ||Fruit fly |
|SNF4Agamma ||SNF4/AMP-activated protein kinase gamma subunit ||Deletion of SNF4Agamma from the first day of the imaginal stage shortens mean lifespan by 23% and causes morphological and behavioural features of premature aging . ||Fruit fly |
|Rbp9 ||RNA-binding protein 9 ||Rbp9 mutation significantly decreases longevity with a 33% reduction in median lifespan of males . ||Fruit fly |
|Prx5 ||Peroxiredoxin 5 ||Prx5 overexpression causes an increase in mean and median lifespan under normal conditions. It also leads to a small increase in maximum lifespan.
dprx5(-/-) null mutants are comparatively more susceptible to oxidative stress, have higher incidence of apoptosis, and a shortened mean lifespan, but thee is no significant difference in maximum lifespan (10% survival) . ||Fruit fly |
|pex16 ||peroxin 16 ||pex16 mutation lead to a reduced mean lifespan of one-third in females and on-fourth in males. The short lifespan can be rescued by the simultaneous overexpression of pex16 in the fat body and differentiated neurons .
Mutant flies lack normal peroxisomes, have an reduced adult body size (70%-85% smaller than controls) and rozy eyes, show locomotion defects in the development of the nervous system . ||Fruit fly |
|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 . ||Fruit fly |
|Mlp84B ||Muscle LIM protein at 84B ||RNA interference of Mlp84B specifically in the heart results in bradycardia and heart rthym abnormalities as well as a shorter mean lifespan in males but not in females . ||Fruit fly |
|mle ||maleless ||Homozygous mutant animals (mle napts) display a shortened median lifespan and increased frailty in both males and females . ||Fruit fly |
|kermit ||— ||The disruption of kermit (alias dGIPC) function results in premature loss of locomotor activity and reduced mean lifespan . ||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) .
||Fruit fly |
|elav ||embryonic lethal abnormal vision ||elav mutation significantly decreases the lifespan. Median lifespan in males is 66% lower . ||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 . ||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% . ||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 . ||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 . ||Fruit fly |
|tert ||telomerase reverse transcriptase ||First-generation tert(-/-) zebrafish die prematurely with shorter telomeres. tert(-/-) fish develop degenerative phenotypes, including premature infertility, gastrointestinal atrophy, and sarcopenia. tert(-/-) mutants have impaired cell proliferation, accumulation of DNA damage markers, and a p53 response leading to early apoptosis, followed by accumulation of senescence cells. Apoptosis is primarily observed in the proliferative niche and germ cells. Cell proliferation, but not apoptosis, is rescued in tp53(-/-)tert(-/-) mutants, underscoring p53 as mediator of telomerase deficiency and consequent telomere instability [http://denigma.de/url/3p]. ||Zebrafish |
|Wrn ||— ||Mice lacking the helicase domain of the WRN ortholog exhibit many phenotypic features of Werner Syndrom, including a pro-oxidant status and a shorter mean lifespan. Mice with a deletion in the helicase domain  recapitulates most of the Werner syndrome phenotypes, including an abnormal hyaluronic acid excretion, higher reactive oxygen species levels, dyslipidemia, increased genomic instability, and cancer incidence. Wrn(Dehl/Dehl) mutant mice have a 10 - 15% decrease in their mean lifespan [12707040; 19741171]. ||House mouse |
|wrn-1 ||human WRN (Werner's syndrome) related ||RNAi kockdown of wrn-1 shortens the lifespan, increases sensitivity to DNA damage, and accelerates aging phenoypes .
A nonfunctional wrn-1 DNA helicase decreases the lifespan. The expression of miR-124 in whole wrn-1 mutant worms is significantly reduced. Supplementation with vitamin C normalizes the median lifespan of wnr-1 and mir-124 mutants . ||Nematode |
|mir-124 ||— ||Loss of mir-124 increases reactive oxygen species formation and accumulation of the aging marker lipofuscin, reduces whole body ATP levels and results in reduction in lifespan .
Supplementation of vitamin C normalizes the reduced median lifespan of mir-124 mutants .
The expression of the conserved mir-124 in whole wrn-1 mutants (which premature age) is significantly reduced . ||Nematode |
|mir-58 ||— ||mir-58(n4640) mutation decreases the mean lifespan by 20% . ||Nematode |
|mir-14 ||mir-14 stem loop ||Mutating mir-14 decreases lifespan in both sexes. mir-14 reduces the mean and maximum lifespan of females by 55 and 36%, respectively, while those of males is reduced by 29 and 21%, respectively .
||Fruit fly |
|mir-246 ||— ||Mutating mir-246 decreases mean and maximum lifespan by 12%, while its overexpression increases mean and maximum lifespan by 6 and 5 - 14%, respectively . ||Nematode |
|mir-238 ||— ||Mutating mir-238 decreases mean and maximum lifespan by 18 and 24% . mir-238(n4112) mutation decreases mean lifespan by 20% . ||Nematode |
|mir-71 ||— ||Loss and gain-of-function of mir-71 decreases and increases lifespan, respectively . mir-71 mutants have a reduced lifespan with 40% decrease in mean lifespan, while extra copies of mir-71 extend the lifespan with an increase in lifespan by 15 - 25% ,
Loss of mir-71 function suppresses the long lifespan of glp-1(e2141) mutants ,
During adulthood mir-71 is strongly expressed in the intestine, body wall muscles and neurons. mir-71 is upregulated in aging adults , ||Nematode |