NAD
Adult Stem Cells
/ cytology
Aging
/ drug effects
Animals
Carbazoles
/ pharmacology
Cell Proliferation
/ drug effects
Cells, Cultured
Dextran Sulfate
/ administration & dosage
Intestinal Mucosa
/ cytology
Male
Mice
Mice, Inbred C57BL
NAD
/ metabolism
Niacinamide
/ administration & dosage
Pyridinium Compounds
Rejuvenation
Sirolimus
/ pharmacology
NAD+
aging
intestinal stem cells
nicotinamide riboside
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
13
06
2017
revised:
05
01
2019
accepted:
03
02
2019
pubmed:
28
3
2019
medline:
15
9
2020
entrez:
28
3
2019
Statut:
ppublish
Résumé
The tissue decline due to aging is associated with the deterioration of adult stem cell function. Here we show the number and proliferative activity of intestinal stem cells (ISCs) but not Paneth cells decline during aging, as does ISC function assessed ex vivo. Levels of SIRT1 and activity of mTORC1 also decline with aging. The treatment with the NAD(+) precursor nicotinamide riboside (NR) rejuvenates ISCs from aged mice and reverses an impaired ability to repair gut damage. The effect of NR is blocked by the mTORC1 inhibitor rapamycin or the SIRT1 inhibitor EX527. These findings demonstrate that small molecules affecting the NAD/SIRT1/mTORC1 axis may guide a translational path for maintenance of the intestine during aging.
Identifiants
pubmed: 30917412
doi: 10.1111/acel.12935
pmc: PMC6516145
doi:
Substances chimiques
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide
0
Carbazoles
0
Pyridinium Compounds
0
nicotinamide-beta-riboside
0I8H2M0L7N
NAD
0U46U6E8UK
Niacinamide
25X51I8RD4
Dextran Sulfate
9042-14-2
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12935Subventions
Organisme : JSPS KAKENHI
ID : JP17H06631
Pays : International
Organisme : Ube Industries Foundation
Pays : International
Organisme : Glenn Foundation for Medical Research
Pays : International
Organisme : Takeda Science Foundation
Pays : International
Organisme : Yakult Bio-Science Foundation
Pays : International
Organisme : Manpei Suzuki Diabetes Foundation
Pays : International
Organisme : Foundation for the National Institutes of Health
Pays : International
Informations de copyright
© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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