TY - JOUR
T1 - Interleukin-6 neutralization ameliorates symptoms in prematurely aged mice
AU - Squarzoni, Stefano
AU - Schena, Elisa
AU - Sabatelli, Patrizia
AU - Mattioli, Elisabetta
AU - Capanni, Cristina
AU - Cenni, Vittoria
AU - D'Apice, Maria Rosaria
AU - Andrenacci, Davide
AU - Sarli, Giuseppe
AU - Pellegrino, Valeria
AU - Festa, Anna
AU - Baruffaldi, Fabio
AU - Storci, Gianluca
AU - Bonafè, Massimiliano
AU - Barboni, Catia
AU - Sanapo, Mara
AU - Zaghini, Anna
AU - Lattanzi, Giovanna
N1 - © 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
PY - 2021/1
Y1 - 2021/1
N2 - 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 LmnaG609G/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.
AB - 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 LmnaG609G/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.
KW - accelerated aging
KW - ageing
KW - anti-aging
KW - cellular senescence
KW - cytokines
KW - inflammation
KW - laminopathies
KW - nuclear lamina
U2 - 10.1111/acel.13285
DO - 10.1111/acel.13285
M3 - Article
C2 - 33393189
VL - 20
SP - 1
EP - 17
JO - Aging Cell
JF - Aging Cell
SN - 1474-9718
IS - 1
ER -