Rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time

Abstract Accumulation of progerin is believed to underlie the pathophysiology of Hutchinson-Gilford progeria syndrome, a disease characterized by clinical features suggestive of premature aging, including loss of subcutaneous white adipose tissue (sWAT). Although progerin has been found in cells and...

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Autores principales:	Gwladys Revêchon, Nikenza Viceconte, Tomás McKenna, Agustín Sola Carvajal, Peter Vrtačnik, Peter Stenvinkel, Torbjörn Lundgren, Kjell Hultenby, Irene Franco, Maria Eriksson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ccc79d39571149198d742b1696417602
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spelling	oai:doaj.org-article:ccc79d39571149198d742b16964176022021-12-02T15:06:10ZRare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time10.1038/s41598-017-04492-02045-2322https://doaj.org/article/ccc79d39571149198d742b16964176022017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04492-0https://doaj.org/toc/2045-2322Abstract Accumulation of progerin is believed to underlie the pathophysiology of Hutchinson-Gilford progeria syndrome, a disease characterized by clinical features suggestive of premature aging, including loss of subcutaneous white adipose tissue (sWAT). Although progerin has been found in cells and tissues from apparently healthy individuals, its significance has been debated given its low expression levels and rare occurrence. Here we demonstrate that sustained progerin expression in a small fraction of preadipocytes and adipocytes of mouse sWAT (between 4.4% and 6.7% of the sWAT cells) results in significant tissue pathology over time, including fibrosis and lipoatrophy. Analysis of sWAT from mice of various ages showed senescence, persistent DNA damage and cell death that preceded macrophage infiltration, and systemic inflammation. Our findings suggest that continuous progerin expression in a small cell fraction of a tissue contributes to aging-associated diseases, the adipose tissue being particularly sensitive.Gwladys RevêchonNikenza ViceconteTomás McKennaAgustín Sola CarvajalPeter VrtačnikPeter StenvinkelTorbjörn LundgrenKjell HultenbyIrene FrancoMaria ErikssonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gwladys Revêchon Nikenza Viceconte Tomás McKenna Agustín Sola Carvajal Peter Vrtačnik Peter Stenvinkel Torbjörn Lundgren Kjell Hultenby Irene Franco Maria Eriksson Rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time
description	Abstract Accumulation of progerin is believed to underlie the pathophysiology of Hutchinson-Gilford progeria syndrome, a disease characterized by clinical features suggestive of premature aging, including loss of subcutaneous white adipose tissue (sWAT). Although progerin has been found in cells and tissues from apparently healthy individuals, its significance has been debated given its low expression levels and rare occurrence. Here we demonstrate that sustained progerin expression in a small fraction of preadipocytes and adipocytes of mouse sWAT (between 4.4% and 6.7% of the sWAT cells) results in significant tissue pathology over time, including fibrosis and lipoatrophy. Analysis of sWAT from mice of various ages showed senescence, persistent DNA damage and cell death that preceded macrophage infiltration, and systemic inflammation. Our findings suggest that continuous progerin expression in a small cell fraction of a tissue contributes to aging-associated diseases, the adipose tissue being particularly sensitive.
format	article
author	Gwladys Revêchon Nikenza Viceconte Tomás McKenna Agustín Sola Carvajal Peter Vrtačnik Peter Stenvinkel Torbjörn Lundgren Kjell Hultenby Irene Franco Maria Eriksson
author_facet	Gwladys Revêchon Nikenza Viceconte Tomás McKenna Agustín Sola Carvajal Peter Vrtačnik Peter Stenvinkel Torbjörn Lundgren Kjell Hultenby Irene Franco Maria Eriksson
author_sort	Gwladys Revêchon
title	Rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time
title_short	Rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time
title_full	Rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time
title_fullStr	Rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time
title_full_unstemmed	Rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time
title_sort	rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ccc79d39571149198d742b1696417602
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Rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time

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