Sci. Aging Knowl. Environ., 3 May 2006
Vol. 2006, Issue 8, p. or9


Lamin A-Dependent Nuclear Defects in Human Aging

Paola Scaffidi, and Tom Misteli

Abstract: Science 27 April 2006 (10.1126/science.1127168) (Science Express Report)

Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford Progeria (HGPS). Whether lamin A plays any role in the normal aging process is unknown. Here, we show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire similar defects as 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.


Science of Aging Knowledge Environment. ISSN 1539-6150