|mir-34 upregulation ||mir-34 upregulation extends median lifespan and mitigated neurodegeneration induced by polyglutamine. ||Fly ||— ||— ||— |
|Jafrac1 overexpression ||Neuronal overexpression of Jafrac1 significantly increases both mean and maximum lifespan, while neuronal knockdown as well as loss of function mutation, causes a reduction in lifespan by 30%. The mean lifespan is 26% and 29% higher in females and males, respectively. The maximum lifespan is increased by 22% and 26% in females and males, respectively .
There is a consistent and significant lifespan extension (15% mean lifespan increase) in both males and females when Jafrac1 is overexpressed in somatic cells. Jafrac1 overexpression using the weaker 5961FS driver moderately but significantly extends lifespan . ||Fly ||+15 to +29 ||+22 to +26 ||— |
|Gclm overexpression ||Overexpression of Gclm extends the mean lifespan by up to 24% . ||Fly ||+24 ||— ||— |
|Gclc overexpression ||Overexpression of Gclc extended mean and maximum lifespan by up to 50% . ||Fly ||+50 ||— ||+50 |
|Foxm1 overexpression ||Increased hepatocyte expression in 12-month-old (aged) transgenic mice of Foxm1b alone is sufficient to restore hepatocyte proliferation to levels found in 2-month-old (young) regenerating liver . ||Mouse ||— ||— ||— |
|Pdf overexpression ||Overexpression of Pdf suppresses age-associated changes in the period and strength of free-running locomotor rhythms and amplifies TIM oscillations in many pacemaker neurons in the elder flies . ||Fly ||— ||— ||— |
|Bub1b overexpression ||Sustained high-level expression of BubR1 preserves genomic integrity and reduces tumorgenesis (even in the presence of genetic alterations that strongly promote aneuplodization and cancer, such as oncogenic Ras) and extends the lifespan and delays age-related deterioriation and aneuploidy in several tissues .
BubR1 overabundance exerts its protective effect by correcting mitotic checkpoints defects .
BubB1 overexpression extends maximum lifespan by 20 - 41% compared to GFP-carrying control transgenic mice . ||Mouse ||— ||— ||+20 to +41.3 |
|mir-239 overexpression ||Overexpressing mir-239 decreases mean and maximum lifespan by 13 and 17 - 33%, respectively . ||Worm ||-13 ||— ||-17 to -33 |
|mir-246 overexpression ||mir-246 overexpression increases mean and maximum lifespan by 6 and 5 - 14%, respectively . ||Worm ||+6.3 ||— ||+4.8 to +14.3 |
|mir-71 overexpression ||Gain-of-function of mir-71 increases lifespan . Extra copies of mir-71 extend the lifespan with an increase in lifespan by 15 - 25% , ||Worm ||+15 to +25 ||— ||— |
|lin-4 overexpression ||Overexpressing lin-4 extends lifespan . ||Worm ||— ||— ||— |
|gig overexpression ||Overexpression of gig, also known as dTsc2, results in lifespan extension. Overexpression of dTsc2 increases mean lifespan by 20% and 12%, at 25°C and 29°C, respectively, and protects from deleterious effects of rich food, as if mimicking the effect of DR .
Overexpression of dTsc2 via a UAS promoter in the eye using the driver gmr-GAL4 or in the nervous system by using appI-GAL4 does not extend the lifespan. Using the drivers 24BGAL4 and PO188-GAL4, enhancer traps that are predominantly expressed in the muscle and fat results in mean lifespan extension of 27% and 37%, respectively, at 29°C . Fat-specific drivers DJ634-GAL4 and PO163-GAL4 when used to overexpress dTsc2, also led to a mean lifespan extension of 22% and 31%, respectively, at 29°C . ||Fly ||+20 to +31 ||— ||— |
|VPH2 overexpression ||Overexpression of VPH2 increases the levels of assembled V-ATPase at the vacuolar membrane, increases vacuolar acidity and suppresses age-induced mitochondrial dysfunction of aged cells (17 or 18 cell divisions) which requires the V-ATPase activity. VPH2 overexpression significantly increases mean, median and maximum replicative lifespan by 23, 25 and 34%, respectively .
||Yeast ||+23.1 ||+25.0 ||+34.0 |
|VMA1 overexpression ||Overexpression of VMA1 increases vacuolar acidity and suppresses age-induced mitochondrial dysfunction of aged cells (17 or 18 cell divisions) which requires the V-ATPase activity. VMA1 overexpression significantly increases mean, median and maximum lifespan by 39 - 45%, 39 - 48% and 50 - 60%, respectively. DR (0.5% glucose restriction) does not further increase the lifespan of VMA1 overexpression strain . ||Yeast ||+39.3 to +44.8 ||+39.3 to +48.3 ||+50.0 to +60.0 |
|Lamp2a expression restoration ||Maintaining the amount of the Lamp2a (in a double transgenic mice) specifically in the liver at levels found in young adults prevents age-dependent decrease in receptor abundance at the cellular and organ levels. In this mice CMA activity is maintained until advanced ages which results in preservation of the autophagic activity and is associated with lower intracellular accumulation of damaged proteins, better ability to handle protein damage and improved organ function [19115216; 18690243]. Lamp2a expression restored not only CMA but also macrophagy and proteasomal degradation to the level observed in young liver as well as youthful mitochondrial function and cellular ATP abundance and overall youthful liver functions . ||Mouse ||— ||— ||— |
|jnk-1 overexpression ||Overexpression of jnk-1 increases lifespan by 40% [15767565; 23097426].
JNK-1 overexpression extends the lifespan in a daf-16-dependent manner. JNK-1 overexpression does not extend the lifespan of animals unable to synthesize miRNAs, i.e. pash-1(mj100) . ||Worm ||+40 ||— ||— |
|lin-14 gain-of-function mutation ||A gain-of-function mutation in lin-14 decreases lifespan . ||Worm ||— ||— ||— |
|PEP4 overexpression ||Overexpression of vacuolar aspartyl protease (PEP4) extends chronological lifespan by increasing cytosolic polyamine and S-adenosylmethionine (SAM) levels. Deletion of PEP4 results in both apoptotic and necrotic cell death during chronological aging . ||Yeast ||— ||— ||— |
|CG13890 overexpression ||Overexpression of CG13890 (DCI) throughout the whole body increases mean and median lifespan by 35 and 31%, but decreases maximum lifespan by 6%, increases stress resistant (to paraquat and starvation), consistently reduces the mortality rate across adult ages and reduces the lifespan extension of DR by 15% .
CG6783 overexpression increases the dFOXO nuclear localization in the fat-body. mRNA levels of dFOXO target genes l(2)efl and 4E-BP in the adult whole bodies increases in response to overexpression of CG6783 . ||Fly ||+35 ||+31 ||+6 |
|fabp overexpression ||Overexpression of fabp (CG6783) throughout the whole body increases mean, median and maximum lifespan by 77, 81 and 13%, increases stress resistant (to paraquat but not starvation), consistently reduces mortality rate across adult ages and reduces the lifespan extension of DR by 12% .
fabp overexpression increases the dFOXO nuclear localization in the fat-body. mRNA levels of dFOXO target genes l(2)efl and 4E-BP in the adult whole bodies increases in response to overexpression of fabp .
Females of the genotype Act-GS-Gal4 > UAS-CG6783 exhibit an increase in median lifespan compared to uninduced control in response to feeding with RU486-containing food from day 3 of adulthood (P < 0.0001). Mean lifespan is extended by 10, while maximum lifespan is decreased by 11% . ||Fly ||+77 ||+81 ||+13 |
|CG10916 overexpression ||Overexpression of CG10916 in males increases mean and maximum lifespan by 27% and 26%, respectively . ||Fly ||+27 ||— ||+26 |
|sm overexpression ||Overexpression of sm in males increases mean and maximum lifespan by 29% and and 16%, respectively . ||Fly ||— ||— ||— |
|SIFR overexpression ||Overexpression of SIFR in males extends mean and maximum lifespan by 23% and 3%, respectively . ||Fly ||+23 ||— ||+3 |
|CG10383 overexpression ||Overexpression of CG10383 in males increases mean and maximum lifespan by 12% and 8%, respectively . ||Fly ||+12 ||— ||+8 |
|Hsp23 overexpression ||Overexpression of Hsp23 increases mean lifespan by more than 30% and increases the premortality phase . ||Fly ||+30 ||— ||— |