Re‐equilibration of imbalanced NAD metabolism ameliorates the impact of telomere dysfunction
Abstract: Short telomeres are a principal defining feature of telomere biology disorders, such as dyskeratosis congenita (DC), for which there are no effective treatments. Here, we report that primary fibroblasts from DC patients and late generation telomerase knockout mice display lower nicotinamide adenine dinucleotide (NAD) levels, and an imbalance in the NAD metabolome that includes elevated CD38 NADase and reduced poly (ADP‐ribose) polymerase and SIRT1 activities, respectively, affecting many associated biological pathways. Supplementation with the NAD precursor, nicotinamide riboside, and CD38 inhibition improved NAD homeostasis, thereby alleviating telomere damage, defective mitochondrial biosynthesis and clearance, cell growth retardation, and cellular senescence of DC fibroblasts. These findings reveal a direct, underlying role of NAD dysregulation when telomeres are short and underscore its relevance to the pathophysiology and interventions of human telomere‐driven diseases.
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Bibliographic citation
-
Re‐equilibration of imbalanced NAD metabolism ameliorates the impact of telomere dysfunction ; volume:39 ; number:21 ; year:2020 ; extent:15
The EMBO journal / European Molecular Biology Organization ; 39, Heft 21 (2020) (gesamt 15)
- Creator
-
Sun, Chongkui
Wang, Kun
Stock, Amanda J.
Gong, Yi
Demarest, Tyler G.
Yang, Beimeng
Giri, Neelam
Harrington, Lea
Alter, Blanche P.
Savage, Sharon A.
Bohr, Vilhelm A.
Liu, Yie
- DOI
-
10.15252/embj.2019103420
- URN
-
urn:nbn:de:101:1-2022062308492369912448
- Rights
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
15.08.2025, 7:22 AM CEST
Data provider
This object is provided by:
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Sun, Chongkui
- Wang, Kun
- Stock, Amanda J.
- Gong, Yi
- Demarest, Tyler G.
- Yang, Beimeng
- Giri, Neelam
- Harrington, Lea
- Alter, Blanche P.
- Savage, Sharon A.
- Bohr, Vilhelm A.
- Liu, Yie
Other Objects (12)
Ultimate government control structures and firm value: Evidence from Chinese listed companies
Performance analysis of ethylene-propylene diene monomer sound-absorbing materials based on image processing recognition
The Effect of Compensation Committee on CEO Compensation Contracts: Evidence from China
Multiple positive solutions for a coupled system of nonlinear impulsive fractional differential equations with parameters
Acetylation of GATA4 on Lysine Residue K313 Promotes Osteoblastic Cells Growth
Impulsive integral BVP for nonlinear integro-differential equation with monotone homomorphism in Banach spaces
A novel scenario in the semi-constrained NMSSM
A novel variation of the recurrent laryngeal nerve
Existence of solutions for the delayed nonlinear fractional functional differential equations with three-point integral boundary value conditions
Retraction Note: Performance analysis of ethylene-propylene diene monomer sound-absorbing materials based on image processing recognition
Product market competition, ultimate controlling structure and related party transactions
Morphology control of zinc oxide nanostructures for application in hybrid solar cells
Ultimate government control structures and firm value: Evidence from Chinese listed companies
Performance analysis of ethylene-propylene diene monomer sound-absorbing materials based on image processing recognition
The Effect of Compensation Committee on CEO Compensation Contracts: Evidence from China
Multiple positive solutions for a coupled system of nonlinear impulsive fractional differential equations with parameters
Acetylation of GATA4 on Lysine Residue K313 Promotes Osteoblastic Cells Growth
Impulsive integral BVP for nonlinear integro-differential equation with monotone homomorphism in Banach spaces
A novel scenario in the semi-constrained NMSSM
A novel variation of the recurrent laryngeal nerve
Existence of solutions for the delayed nonlinear fractional functional differential equations with three-point integral boundary value conditions
Retraction Note: Performance analysis of ethylene-propylene diene monomer sound-absorbing materials based on image processing recognition
Product market competition, ultimate controlling structure and related party transactions
Morphology control of zinc oxide nanostructures for application in hybrid solar cells
Ultimate government control structures and firm value: Evidence from Chinese listed companies
Performance analysis of ethylene-propylene diene monomer sound-absorbing materials based on image processing recognition
The Effect of Compensation Committee on CEO Compensation Contracts: Evidence from China
Multiple positive solutions for a coupled system of nonlinear impulsive fractional differential equations with parameters
Acetylation of GATA4 on Lysine Residue K313 Promotes Osteoblastic Cells Growth
Impulsive integral BVP for nonlinear integro-differential equation with monotone homomorphism in Banach spaces
A novel scenario in the semi-constrained NMSSM
A novel variation of the recurrent laryngeal nerve
Existence of solutions for the delayed nonlinear fractional functional differential equations with three-point integral boundary value conditions
Retraction Note: Performance analysis of ethylene-propylene diene monomer sound-absorbing materials based on image processing recognition
Product market competition, ultimate controlling structure and related party transactions