TY - JOUR
T1 - Knock-down of odr-3 and ife-2 additively extends lifespan and healthspan in C. elegans
AU - Matei, Ioan Valentin
AU - Samukange, Vimbai Netsai Charity
AU - Bunu, Gabriela
AU - Toren, Dmitri
AU - Ghenea, Simona
AU - Tacutu, Robi
N1 - Publisher Copyright:
© 2021 Matei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/9/15
Y1 - 2021/9/15
N2 - Genetic manipulations can ameliorate the aging process and extend the lifespan of model organisms. The aim of this research was to identify novel genetic interventions that promote both lifespan and healthspan, by combining the effects of multiple longevity-associated gene inactivations in C. elegans. For this, the individual and combined effects of the odr-3 mutation and of ife-2 and cku-70 knock-downs were studied, both in the wild type and daf-16 mutant backgrounds. We found that besides increasing the lifespan of wild type animals, the knock-down of ife-2 (starting at L4) also extends the lifespan and healthspan of long-lived odr-3 mutants. In the daf-16 background, ife-2 and odr-3 impairment exert opposing effects individually, while the daf-16; odr-3; ife-2 deficient animals show a similar lifespan and healthspan as daf-16, suggesting that the odr-3 and ife-2 effector outcomes converge downstream of DAF-16. By contrast, cku-70 knock-down did not extend the lifespan of single or double odr-3; ife-2 inactivated animals, and was slightly deleterious to healthspan. In conclusion, we report that impairment of odr-3 and ife-2 increases lifespan and healthspan in an additive and synergistic manner, respectively, and that this result is not improved by further knocking-down cku-70.
AB - Genetic manipulations can ameliorate the aging process and extend the lifespan of model organisms. The aim of this research was to identify novel genetic interventions that promote both lifespan and healthspan, by combining the effects of multiple longevity-associated gene inactivations in C. elegans. For this, the individual and combined effects of the odr-3 mutation and of ife-2 and cku-70 knock-downs were studied, both in the wild type and daf-16 mutant backgrounds. We found that besides increasing the lifespan of wild type animals, the knock-down of ife-2 (starting at L4) also extends the lifespan and healthspan of long-lived odr-3 mutants. In the daf-16 background, ife-2 and odr-3 impairment exert opposing effects individually, while the daf-16; odr-3; ife-2 deficient animals show a similar lifespan and healthspan as daf-16, suggesting that the odr-3 and ife-2 effector outcomes converge downstream of DAF-16. By contrast, cku-70 knock-down did not extend the lifespan of single or double odr-3; ife-2 inactivated animals, and was slightly deleterious to healthspan. In conclusion, we report that impairment of odr-3 and ife-2 increases lifespan and healthspan in an additive and synergistic manner, respectively, and that this result is not improved by further knocking-down cku-70.
KW - lifespan extension
KW - genetic interventions
KW - synergism
KW - ife-2
KW - odr-3
KW - RNA-Binding Proteins/genetics
KW - Forkhead Transcription Factors/genetics
KW - Gene Knockdown Techniques
KW - Animals
KW - Caenorhabditis elegans/genetics
KW - RNA Interference
KW - DNA-Binding Proteins/genetics
KW - Eukaryotic Initiation Factors/genetics
KW - Longevity/genetics
KW - GTP-Binding Protein alpha Subunits, Gi-Go/genetics
KW - Mutation
KW - Caenorhabditis elegans Proteins/genetics
KW - Gene Expression Regulation/drug effects
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UR - http://www.scopus.com/inward/citedby.url?scp=85115654518&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/b11ec38e-4a7f-3cca-a28b-27cb71679ce0/
U2 - 10.18632/aging.203518
DO - 10.18632/aging.203518
M3 - Article (journal)
C2 - 34506301
SN - 1945-4589
VL - 13
SP - 21040
EP - 21065
JO - Aging
JF - Aging
IS - 17
ER -
