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Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function

Human colonic neuromuscular functions decline among the elderly. The aim was to explore the involvement of senescence. A preliminary PCR study looked for age-dependent differences in expression of CDKN1A (encoding the senescence-related p21 protein) and CDKN2A (encoding p16 and p14) in human ascendi...

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Autores principales: Palmer, Alexandra, Epton, Sarah, Crawley, Ellie, Straface, Marilisa, Gammon, Luke, Edgar, Meghan M., Xu, Yichen, Elahi, Shezan, Chin-Aleong, Joanne, Martin, Joanne E., Bishop, Cleo L., Knowles, Charles H., Sanger, Gareth J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529329/
https://www.ncbi.nlm.nih.gov/pubmed/34690683
http://dx.doi.org/10.3389/fnins.2021.747067
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author Palmer, Alexandra
Epton, Sarah
Crawley, Ellie
Straface, Marilisa
Gammon, Luke
Edgar, Meghan M.
Xu, Yichen
Elahi, Shezan
Chin-Aleong, Joanne
Martin, Joanne E.
Bishop, Cleo L.
Knowles, Charles H.
Sanger, Gareth J.
author_facet Palmer, Alexandra
Epton, Sarah
Crawley, Ellie
Straface, Marilisa
Gammon, Luke
Edgar, Meghan M.
Xu, Yichen
Elahi, Shezan
Chin-Aleong, Joanne
Martin, Joanne E.
Bishop, Cleo L.
Knowles, Charles H.
Sanger, Gareth J.
author_sort Palmer, Alexandra
collection PubMed
description Human colonic neuromuscular functions decline among the elderly. The aim was to explore the involvement of senescence. A preliminary PCR study looked for age-dependent differences in expression of CDKN1A (encoding the senescence-related p21 protein) and CDKN2A (encoding p16 and p14) in human ascending and descending colon (without mucosa) from 39 (approximately 50: 50 male: female) adult (aged 27–60 years) and elderly donors (70–89 years). Other genes from different aging pathways (e.g., inflammation, oxidative stress, autophagy) and cell-types (e.g., neurons, neuron axonal transport) were also examined. Unlike CDKN1A, CDKN2A (using primers for p16 and p14 but not when using p14-specific primers) was upregulated in both regions of colon. Compared with the number of genes appearing to upregulate in association with temporal age, more genes positively associated with increased CDKN2A expression (respectively, 16 and five of 44 genes studied for ascending and descending colon). Confirmation of increased expression of CDKN2A was sought by immunostaining for p16 in the myenteric plexus of colon from 52 patients, using a semi-automated software protocol. The results showed increased staining not within the glial cells (S100 stained), but in the cytoplasm of myenteric nerve cell bodies (MAP2 stained, with identified nucleus) of ascending, but not descending colon of the elderly, and not in the cell nucleus of either region or age group (5,710 neurons analyzed: n = 12–14 for each group). It was concluded that increased p16 staining within the cytoplasm of myenteric nerve cell bodies of elderly ascending (but not descending) colon, suggests a region-dependent, post-mitotic cellular senescence-like activity, perhaps involved with aging of enteric neurons within the colon.
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spelling pubmed-85293292021-10-22 Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function Palmer, Alexandra Epton, Sarah Crawley, Ellie Straface, Marilisa Gammon, Luke Edgar, Meghan M. Xu, Yichen Elahi, Shezan Chin-Aleong, Joanne Martin, Joanne E. Bishop, Cleo L. Knowles, Charles H. Sanger, Gareth J. Front Neurosci Neuroscience Human colonic neuromuscular functions decline among the elderly. The aim was to explore the involvement of senescence. A preliminary PCR study looked for age-dependent differences in expression of CDKN1A (encoding the senescence-related p21 protein) and CDKN2A (encoding p16 and p14) in human ascending and descending colon (without mucosa) from 39 (approximately 50: 50 male: female) adult (aged 27–60 years) and elderly donors (70–89 years). Other genes from different aging pathways (e.g., inflammation, oxidative stress, autophagy) and cell-types (e.g., neurons, neuron axonal transport) were also examined. Unlike CDKN1A, CDKN2A (using primers for p16 and p14 but not when using p14-specific primers) was upregulated in both regions of colon. Compared with the number of genes appearing to upregulate in association with temporal age, more genes positively associated with increased CDKN2A expression (respectively, 16 and five of 44 genes studied for ascending and descending colon). Confirmation of increased expression of CDKN2A was sought by immunostaining for p16 in the myenteric plexus of colon from 52 patients, using a semi-automated software protocol. The results showed increased staining not within the glial cells (S100 stained), but in the cytoplasm of myenteric nerve cell bodies (MAP2 stained, with identified nucleus) of ascending, but not descending colon of the elderly, and not in the cell nucleus of either region or age group (5,710 neurons analyzed: n = 12–14 for each group). It was concluded that increased p16 staining within the cytoplasm of myenteric nerve cell bodies of elderly ascending (but not descending) colon, suggests a region-dependent, post-mitotic cellular senescence-like activity, perhaps involved with aging of enteric neurons within the colon. Frontiers Media S.A. 2021-10-07 /pmc/articles/PMC8529329/ /pubmed/34690683 http://dx.doi.org/10.3389/fnins.2021.747067 Text en Copyright © 2021 Palmer, Epton, Crawley, Straface, Gammon, Edgar, Xu, Elahi, Chin-Aleong, Martin, Bishop, Knowles and Sanger. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Palmer, Alexandra
Epton, Sarah
Crawley, Ellie
Straface, Marilisa
Gammon, Luke
Edgar, Meghan M.
Xu, Yichen
Elahi, Shezan
Chin-Aleong, Joanne
Martin, Joanne E.
Bishop, Cleo L.
Knowles, Charles H.
Sanger, Gareth J.
Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function
title Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function
title_full Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function
title_fullStr Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function
title_full_unstemmed Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function
title_short Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function
title_sort expression of p16 within myenteric neurons of the aged colon: a potential marker of declining function
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529329/
https://www.ncbi.nlm.nih.gov/pubmed/34690683
http://dx.doi.org/10.3389/fnins.2021.747067
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