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

Autor: Gwladys Revêchon, Nikenza Viceconte, Tomás McKenna, Agustín Sola Carvajal, Peter Vrtačnik, Peter Stenvinkel, Torbjörn Lundgren, Kjell Hultenby, Irene Franco, Maria Eriksson
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
Druh dokumentu: article
ISSN: 2045-2322
39571149
DOI: 10.1038/s41598-017-04492-0
Popis: 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.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje