NAD(+) supplementation rejuvenates aged gut adult stem cells

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 mTORC...

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Detalles Bibliográficos
Autores principales: Igarashi, Masaki, Miura, Masaomi, Williams, Eric, Jaksch, Frank, Kadowaki, Takashi, Yamauchi, Toshimasa, Guarente, Leonard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Original Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516145/
https://www.ncbi.nlm.nih.gov/pubmed/30917412
http://dx.doi.org/10.1111/acel.12935
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author Igarashi, Masaki
Miura, Masaomi
Williams, Eric
Jaksch, Frank
Kadowaki, Takashi
Yamauchi, Toshimasa
Guarente, Leonard
author_facet Igarashi, Masaki
Miura, Masaomi
Williams, Eric
Jaksch, Frank
Kadowaki, Takashi
Yamauchi, Toshimasa
Guarente, Leonard
author_sort Igarashi, Masaki
collection PubMed
description 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.
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spelling pubmed-65161452019-06-01 NAD(+) supplementation rejuvenates aged gut adult stem cells Igarashi, Masaki Miura, Masaomi Williams, Eric Jaksch, Frank Kadowaki, Takashi Yamauchi, Toshimasa Guarente, Leonard Aging Cell Original Articles 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. John Wiley and Sons Inc. 2019-03-27 2019-06 /pmc/articles/PMC6516145/ /pubmed/30917412 http://dx.doi.org/10.1111/acel.12935 Text en © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Igarashi, Masaki
Miura, Masaomi
Williams, Eric
Jaksch, Frank
Kadowaki, Takashi
Yamauchi, Toshimasa
Guarente, Leonard
NAD(+) supplementation rejuvenates aged gut adult stem cells
title NAD(+) supplementation rejuvenates aged gut adult stem cells
title_full NAD(+) supplementation rejuvenates aged gut adult stem cells
title_fullStr NAD(+) supplementation rejuvenates aged gut adult stem cells
title_full_unstemmed NAD(+) supplementation rejuvenates aged gut adult stem cells
title_short NAD(+) supplementation rejuvenates aged gut adult stem cells
title_sort nad(+) supplementation rejuvenates aged gut adult stem cells
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516145/
https://www.ncbi.nlm.nih.gov/pubmed/30917412
http://dx.doi.org/10.1111/acel.12935
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