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Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence

Sirtuin 2 (SIRT2) has been associated to aging and age-related pathologies. Specifically, an age-dependent accumulation of isoform 3 of SIRT2 in the CNS has been demonstrated; however, no study has addressed the behavioral or molecular consequences that this could have on aging. In the present study...

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Autores principales: Sola-Sevilla, Noemi, Ricobaraza, Ana, Hernandez-Alcoceba, Ruben, Aymerich, Maria S., Tordera, Rosa M., Puerta, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003096/
https://www.ncbi.nlm.nih.gov/pubmed/33803627
http://dx.doi.org/10.3390/ijms22063107
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author Sola-Sevilla, Noemi
Ricobaraza, Ana
Hernandez-Alcoceba, Ruben
Aymerich, Maria S.
Tordera, Rosa M.
Puerta, Elena
author_facet Sola-Sevilla, Noemi
Ricobaraza, Ana
Hernandez-Alcoceba, Ruben
Aymerich, Maria S.
Tordera, Rosa M.
Puerta, Elena
author_sort Sola-Sevilla, Noemi
collection PubMed
description Sirtuin 2 (SIRT2) has been associated to aging and age-related pathologies. Specifically, an age-dependent accumulation of isoform 3 of SIRT2 in the CNS has been demonstrated; however, no study has addressed the behavioral or molecular consequences that this could have on aging. In the present study, we have designed an adeno-associated virus vector (AAV-CAG-Sirt2.3-eGFP) for the overexpression of SIRT2.3 in the hippocampus of 2 month-old SAMR1 and SAMP8 mice. Our results show that the specific overexpression of this isoform does not induce significant behavioral or molecular effects at short or long term in the control strain. Only a tendency towards a worsening in the performance in acquisition phase of the Morris Water Maze was found in SAMP8 mice, together with a significant increase in the pro-inflammatory cytokine Il-1β. These results suggest that the age-related increase of SIRT2.3 found in the brain is not responsible for induction or prevention of senescence. Nevertheless, in combination with other risk factors, it could contribute to the progression of age-related processes. Understanding the specific role of SIRT2 on aging and the underlying molecular mechanisms is essential to design new and more successful therapies for the treatment of age-related diseases.
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spelling pubmed-80030962021-03-28 Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence Sola-Sevilla, Noemi Ricobaraza, Ana Hernandez-Alcoceba, Ruben Aymerich, Maria S. Tordera, Rosa M. Puerta, Elena Int J Mol Sci Article Sirtuin 2 (SIRT2) has been associated to aging and age-related pathologies. Specifically, an age-dependent accumulation of isoform 3 of SIRT2 in the CNS has been demonstrated; however, no study has addressed the behavioral or molecular consequences that this could have on aging. In the present study, we have designed an adeno-associated virus vector (AAV-CAG-Sirt2.3-eGFP) for the overexpression of SIRT2.3 in the hippocampus of 2 month-old SAMR1 and SAMP8 mice. Our results show that the specific overexpression of this isoform does not induce significant behavioral or molecular effects at short or long term in the control strain. Only a tendency towards a worsening in the performance in acquisition phase of the Morris Water Maze was found in SAMP8 mice, together with a significant increase in the pro-inflammatory cytokine Il-1β. These results suggest that the age-related increase of SIRT2.3 found in the brain is not responsible for induction or prevention of senescence. Nevertheless, in combination with other risk factors, it could contribute to the progression of age-related processes. Understanding the specific role of SIRT2 on aging and the underlying molecular mechanisms is essential to design new and more successful therapies for the treatment of age-related diseases. MDPI 2021-03-18 /pmc/articles/PMC8003096/ /pubmed/33803627 http://dx.doi.org/10.3390/ijms22063107 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sola-Sevilla, Noemi
Ricobaraza, Ana
Hernandez-Alcoceba, Ruben
Aymerich, Maria S.
Tordera, Rosa M.
Puerta, Elena
Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence
title Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence
title_full Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence
title_fullStr Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence
title_full_unstemmed Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence
title_short Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence
title_sort understanding the potential role of sirtuin 2 on aging: consequences of sirt2.3 overexpression in senescence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003096/
https://www.ncbi.nlm.nih.gov/pubmed/33803627
http://dx.doi.org/10.3390/ijms22063107
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