A triple drug combination targeting components of the nutrient-sensing network maximizes longevity.
Aged
Aging
/ drug effects
Animals
Drosophila
/ drug effects
Drosophila Proteins
/ genetics
Drug Combinations
Female
Glycogen Synthase Kinase 3
/ antagonists & inhibitors
Humans
Lithium
/ pharmacology
Longevity
/ drug effects
Mechanistic Target of Rapamycin Complex 1
/ antagonists & inhibitors
Middle Aged
Nutrients
/ metabolism
Pyridones
/ pharmacology
Pyrimidinones
/ pharmacology
Signal Transduction
/ drug effects
Sirolimus
/ pharmacology
aging
lithium
polypharmacology
rapamycin
trametinib
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
15 10 2019
15 10 2019
Historique:
pubmed:
2
10
2019
medline:
31
3
2020
entrez:
2
10
2019
Statut:
ppublish
Résumé
Increasing life expectancy is causing the prevalence of age-related diseases to rise, and there is an urgent need for new strategies to improve health at older ages. Reduced activity of insulin/insulin-like growth factor signaling (IIS) and mechanistic target of rapamycin (mTOR) nutrient-sensing signaling network can extend lifespan and improve health during aging in diverse organisms. However, the extensive feedback in this network and adverse side effects of inhibition imply that simultaneous targeting of specific effectors in the network may most effectively combat the effects of aging. We show that the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib, the mTOR complex 1 (mTORC1) inhibitor rapamycin, and the glycogen synthase kinase-3 (GSK-3) inhibitor lithium act additively to increase longevity in
Identifiants
pubmed: 31570569
pii: 1913212116
doi: 10.1073/pnas.1913212116
pmc: PMC6800352
doi:
Substances chimiques
Drosophila Proteins
0
Drug Combinations
0
Pyridones
0
Pyrimidinones
0
trametinib
33E86K87QN
Lithium
9FN79X2M3F
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Glycogen Synthase Kinase 3
EC 2.7.11.26
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20817-20819Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK036836
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054215
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122610
Pays : United States
Organisme : Wellcome Trust
ID : 214589/Z/18/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT098565/Z/12/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2019 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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