Genetic repression of the antioxidant enzymes reduces the lifespan in Drosophila melanogaster.
Chemical inhibitors
Longevity
RNAi
Journal
Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology
ISSN: 1432-136X
Titre abrégé: J Comp Physiol B
Pays: Germany
ID NLM: 8413200
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
03
03
2021
accepted:
28
09
2021
revised:
14
09
2021
pubmed:
10
10
2021
medline:
5
3
2022
entrez:
9
10
2021
Statut:
ppublish
Résumé
Aging is a biological process associated with gradual loss of function caused by cellular and molecular damages ultimately leading to mortality. Free radicals are implicated in oxidative damage which affects the longevity of organisms. Natural cellular defenses involving antioxidant enzymes delay or prevent oxidative damage and, therefore, influence the aging process and longevity has been shown in many species including Drosophila. We and others have shown that oxidative resistance is an important mechanism in the aging process in Drosophila. Therefore, we hypothesized that repressing endogenous antioxidant defenses shortens longevity in Drosophila. To study the influence of natural defense mechanisms against oxidative stress in aging, we have investigated the effect of genetic repression of the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), on longevity in Drosophila using transgenic RNAi flies and in vivo inhibition of the enzymes with chemical inhibitors. RNAi lines of Drosophila viz., UAS-sod1-IR and UAS-cat-IR, are driven ubiquitously using Act5C-Gal4 and Tubulin-Gal4 to achieve the suppression of SOD1 and CAT activities, respectively. We show that genetic repression of SOD1 and CAT by RNAi in transgenic flies led to drastically reduced longevity (SOD1, 77%; CAT, 83%), presenting the evidence for the role of endogenous antioxidant defenses in lifespan extension in Drosophila. Further, our study shows that the enzyme inhibitors, diethyldithiocarbamate and 3-amino-1,2,4-triazole, although lower the enzyme activities in vivo in flies, but did not affect longevity, which could be attributed to the factors such as bioavailability and metabolism of the inhibitors and adaptive mechanisms involving de novo synthesis of the enzymes. Our study of genetic repression using transgenic RNAi provides experimental evidence that extended longevity is associated with endogenous antioxidant defenses and aging is correlated with oxidative stress resistance.
Identifiants
pubmed: 34625818
doi: 10.1007/s00360-021-01412-7
pii: 10.1007/s00360-021-01412-7
doi:
Substances chimiques
Antioxidants
0
Superoxide Dismutase
EC 1.15.1.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-13Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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