Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by features of accelerated aging and a life expectancy of about fourteen years. HGPS is commonly caused by a point mutation in the LMNA gene that codes for lamin A, an essential component of the nuclear lamina. The mutation causing HGPS leads to the production of a truncated, farnesylated form of lamin A referred to as "Progerin". Progerin is also produced in small quantities in healthy individuals and has been implicated in normal aging.

HGPS is associated with an accumulation of genomic DNA double-strand breaks (DSBs). The source of DSBs in HGPS is often attributed to stalling and subsequent collapse of replication forks in conjunction with faulty recruitment of repair factors to damage sites. In their new study titled "Progerin can induce DNA damage in the absence of global changes in replication or cell proliferation", former and current graduate students Liza Joudeh and Alannah DiCintio, undergraduate lab member Nina Van, their mentor Dr. Alan Waldman and their collaborators Drs. Logan Schuck and Jason Stewart, used a model system involving immortalized human cell lines to investigate  the levels of endogenous damage in cells expressing progerin compared to levels of damage in cells not expressing progerin. They found that cells engineered to express progerin displayed a significant elevation of endogenous damage in the absence of any change in the cell cycle profile or doubling time of cells. Overall, their new results show that DNA damage caused by progerin can occur independently from global changes in replication or cell proliferation, which challenges a paradigm whereby obstructed replication necessarily serves as the initiating source of progerin-inflicted endogenous DNA damage.