Lamin A-Dependent Nuclear Defects in Human Aging

2006/04/27 by Paola Scaffidi, Tom Misteli · 8 citations
Biochemistry, Genetics and Molecular Biology · #Biology #Cell biology #Cell nucleus #DNA #DNA Repair Mechanisms #Gene #Genetics #Histone #LMNA #Lamin #Nuclear Structure and Function #Nuclear lamina #Nuclear protein #Premature aging #Progeria #RNA Research and Splicing

paper · doi:10.1126/science.1127168

openalex publication_date 2006/04/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/25

Abstract

Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.

Citations

• Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome
• Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome
• Lamin A Truncation in Hutchinson-Gilford Progeria
• Genomic instability in laminopathy-based premature aging
• Age-related changes of nuclear architecture in Caenorhabditis elegans

Cited by

• A dual role for A-type lamins in DNA double-strand break repair
• Phenotype and Course of Hutchinson–Gilford Progeria Syndrome
• The Mutant Form of Lamin A that Causes Hutchinson-Gilford Progeria Is a Biomarker of Cellular Aging in Human Skin
• Nuclear DNA Damage as a Direct Cause of Aging
• Hutchinson–Gilford Progeria Syndrome, Aging, and the Nuclear Lamina
• Global Reorganization of the Nuclear Landscape in Senescent Cells
• Histone methylation: a dynamic mark in health, disease and inheritance
• Progeria [wikipedia]