Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.

Atrophy of the olfactory epithelium (OE) associated with impaired olfaction and dry nose represents one of the most common phenotypes of human aging. Impairment in regeneration of a functional olfactory epithelium can also occur in response to injury due to infection or nasal surgery. These complica...

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Autores principales:	Masami Watabe-Rudolph, Yvonne Begus-Nahrmann, André Lechel, Harshvardhan Rolyan, Marc-Oliver Scheithauer, Gerhard Rettinger, Dietmar Rudolf Thal, Karl Lenhard Rudolph
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/01f0b260a43b4cf4b60e177d94eacfbc
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spelling	oai:doaj.org-article:01f0b260a43b4cf4b60e177d94eacfbc2021-11-18T07:34:06ZTelomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.1932-620310.1371/journal.pone.0027801https://doaj.org/article/01f0b260a43b4cf4b60e177d94eacfbc2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22110763/?tool=EBIhttps://doaj.org/toc/1932-6203Atrophy of the olfactory epithelium (OE) associated with impaired olfaction and dry nose represents one of the most common phenotypes of human aging. Impairment in regeneration of a functional olfactory epithelium can also occur in response to injury due to infection or nasal surgery. These complications occur more frequently in aged patients. Although age is the most unifying risk factor for atrophic changes and functional decline of the olfactory epithelium, little is known about molecular mechanisms that could influence maintenance and repair of the olfactory epithelium. Here, we analyzed the influence of telomere shortening (a basic mechanism of cellular aging) on homeostasis and regenerative reserve in response to chemical induced injury of the OE in late generation telomere knockout mice (G3 mTerc(-/-)) with short telomeres compared to wild type mice (mTerc(+/+)) with long telomeres. The study revealed no significant influence of telomere shortening on homeostatic maintenance of the OE during mouse aging. In contrast, the regenerative response to chemical induced injury of the OE was significantly impaired in G3 mTerc(-/-) mice compared to mTerc(+/+) mice. Seven days after chemical induced damage, G3 mTerc(-/-) mice exhibited significantly enlarged areas of persisting atrophy compared to mTerc(+/+) mice (p = 0.031). Telomere dysfunction was associated with impairments in cell proliferation in the regenerating epithelium. Deletion of the cell cycle inhibitor, Cdkn1a (p21) rescued defects in OE regeneration in telomere dysfunctional mice. Together, these data indicate that telomere shortening impairs the regenerative capacity of the OE by impairing cell cycle progression in a p21-dependent manner. These findings could be relevant for the impairment in OE function in elderly people.Masami Watabe-RudolphYvonne Begus-NahrmannAndré LechelHarshvardhan RolyanMarc-Oliver ScheithauerGerhard RettingerDietmar Rudolf ThalKarl Lenhard RudolphPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27801 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masami Watabe-Rudolph Yvonne Begus-Nahrmann André Lechel Harshvardhan Rolyan Marc-Oliver Scheithauer Gerhard Rettinger Dietmar Rudolf Thal Karl Lenhard Rudolph Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.
description	Atrophy of the olfactory epithelium (OE) associated with impaired olfaction and dry nose represents one of the most common phenotypes of human aging. Impairment in regeneration of a functional olfactory epithelium can also occur in response to injury due to infection or nasal surgery. These complications occur more frequently in aged patients. Although age is the most unifying risk factor for atrophic changes and functional decline of the olfactory epithelium, little is known about molecular mechanisms that could influence maintenance and repair of the olfactory epithelium. Here, we analyzed the influence of telomere shortening (a basic mechanism of cellular aging) on homeostasis and regenerative reserve in response to chemical induced injury of the OE in late generation telomere knockout mice (G3 mTerc(-/-)) with short telomeres compared to wild type mice (mTerc(+/+)) with long telomeres. The study revealed no significant influence of telomere shortening on homeostatic maintenance of the OE during mouse aging. In contrast, the regenerative response to chemical induced injury of the OE was significantly impaired in G3 mTerc(-/-) mice compared to mTerc(+/+) mice. Seven days after chemical induced damage, G3 mTerc(-/-) mice exhibited significantly enlarged areas of persisting atrophy compared to mTerc(+/+) mice (p = 0.031). Telomere dysfunction was associated with impairments in cell proliferation in the regenerating epithelium. Deletion of the cell cycle inhibitor, Cdkn1a (p21) rescued defects in OE regeneration in telomere dysfunctional mice. Together, these data indicate that telomere shortening impairs the regenerative capacity of the OE by impairing cell cycle progression in a p21-dependent manner. These findings could be relevant for the impairment in OE function in elderly people.
format	article
author	Masami Watabe-Rudolph Yvonne Begus-Nahrmann André Lechel Harshvardhan Rolyan Marc-Oliver Scheithauer Gerhard Rettinger Dietmar Rudolf Thal Karl Lenhard Rudolph
author_facet	Masami Watabe-Rudolph Yvonne Begus-Nahrmann André Lechel Harshvardhan Rolyan Marc-Oliver Scheithauer Gerhard Rettinger Dietmar Rudolf Thal Karl Lenhard Rudolph
author_sort	Masami Watabe-Rudolph
title	Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.
title_short	Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.
title_full	Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.
title_fullStr	Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.
title_full_unstemmed	Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.
title_sort	telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/01f0b260a43b4cf4b60e177d94eacfbc
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Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.

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