The flavonoid morin alleviates nuclear deformation in aged cells by disrupting progerin-lamin A/C binding

Abstract

Nuclear lamin A/C plays an important role in maintaining the nuclear envelope structure. Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease caused by a silent mutation in the lamin A/C gene, leading to the production of a C-terminally truncated protein (progerin). A deformed nuclear shape is a hallmark of HGPS cells, which observed in normal aged cells. A recent study has found that progerin can directly interact with lamin A/C, which leads to nuclear deformation. In this study, we identified natural compounds that can disrupt this progerin-mediated interaction. Similar to the synthetic compound JH4, morin disrupted this progerin-mediated interaction. Treatment with 20 mu M morin ameliorated nuclear deformation by more than 50% in progerin-expressing cells. As morin is a naturally occurring substance with anti-oxidative activity, it may be developed as a functional food to improve the lifespan and health of both HGPS patients and normal aging individuals.