Interleukin-6 neutralization ameliorates symptoms in prematurely aged mice

Stefano Squarzoni, Elisa Schena, Patrizia Sabatelli, Elisabetta Mattioli, Cristina Capanni, Vittoria Cenni, Maria Rosaria D'Apice, Davide Andrenacci, Giuseppe Sarli, Valeria Pellegrino, Anna Festa, Fabio Baruffaldi, Gianluca Storci, Massimiliano Bonafè, Catia Barboni, Mara Sanapo, Anna Zaghini, Giovanna Lattanzi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalAging Cell
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 2021

Keywords

  • accelerated aging
  • ageing
  • anti-aging
  • cellular senescence
  • cytokines
  • inflammation
  • laminopathies
  • nuclear lamina

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