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Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan
Cellular senescence, a stress-induced irreversible growth arrest often characterized by p16(Ink4a) expression and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cell...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845101/ https://www.ncbi.nlm.nih.gov/pubmed/26840489 http://dx.doi.org/10.1038/nature16932 |
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author | Baker, Darren J. Childs, Bennett G. Durik, Matej Wijers, Melinde E. Sieben, Cynthia J. Zhong, Jian Saltness, Rachel Jeganathan, Karthik B. Versoza, Grace C. Pezeshki, Abdul-Mohammad Khazaie, Khashayarsha Miller, Jordan D. van Deursen, Jan M. |
author_facet | Baker, Darren J. Childs, Bennett G. Durik, Matej Wijers, Melinde E. Sieben, Cynthia J. Zhong, Jian Saltness, Rachel Jeganathan, Karthik B. Versoza, Grace C. Pezeshki, Abdul-Mohammad Khazaie, Khashayarsha Miller, Jordan D. van Deursen, Jan M. |
author_sort | Baker, Darren J. |
collection | PubMed |
description | Cellular senescence, a stress-induced irreversible growth arrest often characterized by p16(Ink4a) expression and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over time and have been speculated to play a role in aging. To explore the physiological relevance and consequences of naturally occurring senescent cells, we used a previously established transgene, INK-ATTAC, to induce apoptosis in p16(Ink4a)-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. Here we show that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. Clearance of p16(Ink4a)-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective K(ATP) channels, and adipocytes, respectively. Thus, p16(Ink4a)-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in multiple organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan. |
format | Online Article Text |
id | pubmed-4845101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-48451012016-08-03 Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan Baker, Darren J. Childs, Bennett G. Durik, Matej Wijers, Melinde E. Sieben, Cynthia J. Zhong, Jian Saltness, Rachel Jeganathan, Karthik B. Versoza, Grace C. Pezeshki, Abdul-Mohammad Khazaie, Khashayarsha Miller, Jordan D. van Deursen, Jan M. Nature Article Cellular senescence, a stress-induced irreversible growth arrest often characterized by p16(Ink4a) expression and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over time and have been speculated to play a role in aging. To explore the physiological relevance and consequences of naturally occurring senescent cells, we used a previously established transgene, INK-ATTAC, to induce apoptosis in p16(Ink4a)-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. Here we show that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. Clearance of p16(Ink4a)-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective K(ATP) channels, and adipocytes, respectively. Thus, p16(Ink4a)-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in multiple organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan. 2016-02-03 2016-02-11 /pmc/articles/PMC4845101/ /pubmed/26840489 http://dx.doi.org/10.1038/nature16932 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms Reprints and permissions information is available at www.nature.com/reprints. |
spellingShingle | Article Baker, Darren J. Childs, Bennett G. Durik, Matej Wijers, Melinde E. Sieben, Cynthia J. Zhong, Jian Saltness, Rachel Jeganathan, Karthik B. Versoza, Grace C. Pezeshki, Abdul-Mohammad Khazaie, Khashayarsha Miller, Jordan D. van Deursen, Jan M. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan |
title | Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan |
title_full | Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan |
title_fullStr | Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan |
title_full_unstemmed | Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan |
title_short | Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan |
title_sort | naturally occurring p16(ink4a)-positive cells shorten healthy lifespan |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845101/ https://www.ncbi.nlm.nih.gov/pubmed/26840489 http://dx.doi.org/10.1038/nature16932 |
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