Aging looks and feels like it is multifactorial: everything falls apart independently. But now Paola Scaffidi and Tom Misteli (National Cancer Institute, Bethesda, MD) report that multiple hallmarks of cellular aging can be reversed by eliminating one aberrant splicing product of lamin A.
The lamins form a structural cage on the interior surface of the nucleus. Lamin A has a long tail that is first farnesylated and then chopped off. In the 50 or so patients known to have the premature aging syndrome Hutchinson-Gilford Progeria (HGPS), an aberrant splicing event creates a lamin A that gets farnesylated but not cleaved.
The NCI team now shows that normal cells also have a small amount of this aberrant splice product. Although neither the splice product nor its protein product accumulate to higher levels with age, their effects do. As in HGPS cells, older cells have decreased heterochromatin...
