Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 37, Pages 16268-16273Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1002696107
Keywords
laminopathy; microRNA; progeria; protease; cancer
Categories
Funding
- Ministerio de Ciencia e Innovacion-Spain
- Fundacion M. Botin
- European Union
- Obra Social Cajastur
- Accion Transversal del Cancer-Red Tematica de Investigacion Cooperativa en Cancer
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Zmpste24 (also called FACE-1) is a metalloproteinase involved in the maturation of lamin A, an essential component of the nuclear envelope. Zmpste24-deficient mice exhibit multiple defects that phenocopy human accelerated aging processes such as Hutchinson-Gilford progeria syndrome. In this work, we report that progeroid Zmpste24(-/-) mice present profound transcriptional alterations in genes that regulate the somatotroph axis, together with extremely high circulating levels of growth hormone (GH) and a drastic reduction in plasma insulin-like growth factor 1 (IGF-1). We also show that recombinant IGF-1 treatment restores the proper balance between IGF-1 and GH in Zmpste24(-/-) mice, delays the onset of many progeroid features, and significantly extends the lifespan of these progeroid animals. Our findings highlight the importance of IGF/GH balance in longevity and may be of therapeutic interest for devastating human progeroid syndromes associated with nuclear envelope abnormalities.
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