Senescence-Inflammatory Regulation of Reparative Cellular Reprogramming in Aging and Cancer
The inability of adult tissues to transitorily generate cells with functional stem cell-like properties is a major obstacle to tissue self-repair. Nuclear reprogramming-like phenomena that induce a transient acquisition of epigenetic plasticity and phenotype malleability may constitute a reparative...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2017-05-01
|
Series: | Frontiers in Cell and Developmental Biology |
Subjects: | |
Online Access: | http://journal.frontiersin.org/article/10.3389/fcell.2017.00049/full |
id |
doaj-a61e9b14905a40b790daf39acc9e0b63 |
---|---|
record_format |
Article |
spelling |
doaj-a61e9b14905a40b790daf39acc9e0b632020-11-24T23:21:58ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2017-05-01510.3389/fcell.2017.00049261800Senescence-Inflammatory Regulation of Reparative Cellular Reprogramming in Aging and CancerJavier A. Menendez0Javier A. Menendez1Javier A. Menendez2Tomás Alarcón3Tomás Alarcón4Tomás Alarcón5Tomás Alarcón6Metabolism and Cancer Group, Program Against Cancer Therapeutic Resistance, Catalan Institute of OncologyGirona, SpainMolecular Oncology Group, Girona Biomedical Research Institute (IDIBGI)Girona, SpainMETABOSTEMBarcelona, SpainInstitució Catalana de Recerca i Estudis Avançats (ICREA)Barcelona, SpainComputational and Mathematical Biology Research Group, Centre de Recerca MatemàticaBarcelona, SpainDepartament de Matemàtiques, Universitat Autònoma de BarcelonaBarcelona, SpainBarcelona Graduate School of MathematicsBarcelona, SpainThe inability of adult tissues to transitorily generate cells with functional stem cell-like properties is a major obstacle to tissue self-repair. Nuclear reprogramming-like phenomena that induce a transient acquisition of epigenetic plasticity and phenotype malleability may constitute a reparative route through which human tissues respond to injury, stress, and disease. However, tissue rejuvenation should involve not only the transient epigenetic reprogramming of differentiated cells, but also the committed re-acquisition of the original or alternative committed cell fate. Chronic or unrestrained epigenetic plasticity would drive aging phenotypes by impairing the repair or the replacement of damaged cells; such uncontrolled phenomena of in vivo reprogramming might also generate cancer-like cellular states. We herein propose that the ability of senescence-associated inflammatory signaling to regulate in vivo reprogramming cycles of tissue repair outlines a threshold model of aging and cancer. The degree of senescence/inflammation-associated deviation from the homeostatic state may delineate a type of thresholding algorithm distinguishing beneficial from deleterious effects of in vivo reprogramming. First, transient activation of NF-κB-related innate immunity and senescence-associated inflammatory components (e.g., IL-6) might facilitate reparative cellular reprogramming in response to acute inflammatory events. Second, para-inflammation switches might promote long-lasting but reversible refractoriness to reparative cellular reprogramming. Third, chronic senescence-associated inflammatory signaling might lock cells in highly plastic epigenetic states disabled for reparative differentiation. The consideration of a cellular reprogramming-centered view of epigenetic plasticity as a fundamental element of a tissue's capacity to undergo successful repair, aging degeneration or malignant transformation should provide challenging stochastic insights into the current deterministic genetic paradigm for most chronic diseases, thereby increasing the spectrum of therapeutic approaches for physiological aging and cancer.http://journal.frontiersin.org/article/10.3389/fcell.2017.00049/fullreprogrammingagingcancersenescenceinflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Javier A. Menendez Javier A. Menendez Javier A. Menendez Tomás Alarcón Tomás Alarcón Tomás Alarcón Tomás Alarcón |
spellingShingle |
Javier A. Menendez Javier A. Menendez Javier A. Menendez Tomás Alarcón Tomás Alarcón Tomás Alarcón Tomás Alarcón Senescence-Inflammatory Regulation of Reparative Cellular Reprogramming in Aging and Cancer Frontiers in Cell and Developmental Biology reprogramming aging cancer senescence inflammation |
author_facet |
Javier A. Menendez Javier A. Menendez Javier A. Menendez Tomás Alarcón Tomás Alarcón Tomás Alarcón Tomás Alarcón |
author_sort |
Javier A. Menendez |
title |
Senescence-Inflammatory Regulation of Reparative Cellular Reprogramming in Aging and Cancer |
title_short |
Senescence-Inflammatory Regulation of Reparative Cellular Reprogramming in Aging and Cancer |
title_full |
Senescence-Inflammatory Regulation of Reparative Cellular Reprogramming in Aging and Cancer |
title_fullStr |
Senescence-Inflammatory Regulation of Reparative Cellular Reprogramming in Aging and Cancer |
title_full_unstemmed |
Senescence-Inflammatory Regulation of Reparative Cellular Reprogramming in Aging and Cancer |
title_sort |
senescence-inflammatory regulation of reparative cellular reprogramming in aging and cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2017-05-01 |
description |
The inability of adult tissues to transitorily generate cells with functional stem cell-like properties is a major obstacle to tissue self-repair. Nuclear reprogramming-like phenomena that induce a transient acquisition of epigenetic plasticity and phenotype malleability may constitute a reparative route through which human tissues respond to injury, stress, and disease. However, tissue rejuvenation should involve not only the transient epigenetic reprogramming of differentiated cells, but also the committed re-acquisition of the original or alternative committed cell fate. Chronic or unrestrained epigenetic plasticity would drive aging phenotypes by impairing the repair or the replacement of damaged cells; such uncontrolled phenomena of in vivo reprogramming might also generate cancer-like cellular states. We herein propose that the ability of senescence-associated inflammatory signaling to regulate in vivo reprogramming cycles of tissue repair outlines a threshold model of aging and cancer. The degree of senescence/inflammation-associated deviation from the homeostatic state may delineate a type of thresholding algorithm distinguishing beneficial from deleterious effects of in vivo reprogramming. First, transient activation of NF-κB-related innate immunity and senescence-associated inflammatory components (e.g., IL-6) might facilitate reparative cellular reprogramming in response to acute inflammatory events. Second, para-inflammation switches might promote long-lasting but reversible refractoriness to reparative cellular reprogramming. Third, chronic senescence-associated inflammatory signaling might lock cells in highly plastic epigenetic states disabled for reparative differentiation. The consideration of a cellular reprogramming-centered view of epigenetic plasticity as a fundamental element of a tissue's capacity to undergo successful repair, aging degeneration or malignant transformation should provide challenging stochastic insights into the current deterministic genetic paradigm for most chronic diseases, thereby increasing the spectrum of therapeutic approaches for physiological aging and cancer. |
topic |
reprogramming aging cancer senescence inflammation |
url |
http://journal.frontiersin.org/article/10.3389/fcell.2017.00049/full |
work_keys_str_mv |
AT javieramenendez senescenceinflammatoryregulationofreparativecellularreprogramminginagingandcancer AT javieramenendez senescenceinflammatoryregulationofreparativecellularreprogramminginagingandcancer AT javieramenendez senescenceinflammatoryregulationofreparativecellularreprogramminginagingandcancer AT tomasalarcon senescenceinflammatoryregulationofreparativecellularreprogramminginagingandcancer AT tomasalarcon senescenceinflammatoryregulationofreparativecellularreprogramminginagingandcancer AT tomasalarcon senescenceinflammatoryregulationofreparativecellularreprogramminginagingandcancer AT tomasalarcon senescenceinflammatoryregulationofreparativecellularreprogramminginagingandcancer |
_version_ |
1725569149650862080 |