Open AccessInterleukin‐6 neutralization ameliorates symptoms in prematurely aged mice
Author(s) -
Squarzoni Stefano,
Schena Elisa,
Sabatelli Patrizia,
Mattioli Elisabetta,
Capanni Cristina,
Cenni Vittoria,
D'Apice Maria Rosaria,
Andrenacci Davide,
Sarli Giuseppe,
Pellegrino Valeria,
Festa Anna,
Baruffaldi Fabio,
Storci Gianluca,
Bonafè Massimiliano,
Barboni Catia,
Sanapo Mara,
Zaghini Anna,
Lattanzi Giovanna
Publication year - 2021
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13285
Subject(s) - progeria , lmna , tocilizumab , premature aging , biology , lipodystrophy , immunology , lamin , genetics , rheumatoid arthritis , human immunodeficiency virus (hiv) , gene , antiretroviral therapy , viral load
Hutchinson–Gilford progeria syndrome (HGPS) causes premature aging in children, with adipose tissue, skin and bone deterioration, and cardiovascular impairment. In HGPS cells and mouse models, high levels of interleukin‐6, an inflammatory cytokine linked to aging processes, have been detected. Here, we show that inhibition of interleukin‐6 activity by tocilizumab, a neutralizing antibody raised against interleukin‐6 receptors, counteracts progeroid features in both HGPS fibroblasts and Lmna G609G / G609G progeroid mice. Tocilizumab treatment limits the accumulation of progerin, the toxic protein produced in HGPS cells, rescues nuclear envelope and chromatin abnormalities, and attenuates the hyperactivated DNA damage response. In vivo administration of tocilizumab reduces aortic lesions and adipose tissue dystrophy, delays the onset of lipodystrophy and kyphosis, avoids motor impairment, and preserves a good quality of life in progeroid mice. This work identifies tocilizumab as a valuable tool in HGPS therapy and, speculatively, in the treatment of a variety of aging‐related disorders.