Finding new pathways in accelerated aging disorders

2014

Challenge

Why does neurodegeneration develop in certain accelerated aging disorders, but not in others? Currently available treatments may slow disease progression, but the search continues for therapies that can halt or reverse the damage caused by neurodegenerative diseases.

Advance

IRP researchers led by Vilhelm A. Bohr, M.D., Ph.D., found an abnormality in the energy-supplying cell organelles called mitochondria across several accelerated aging disorders characterized by neurodegeneration. The team pinpointed the cause of the abnormality as a loss of central metabolites triggered by genome instability, and they demonstrated that adding the missing metabolites could restore proper function.

Impact

Dr. Bohr’s research highlights a new pathway that connects genome instability with mitochondrial dysfunction and provides new targets for developing therapeutic interventions for neurodegenerative diseases that currently have no cure.

Publications

Fang EF, Scheibye-Knudsen M, Brace LE, Kassahun H, Sengupta T, Nilsen H, Mitchell JR, Croteau DL, Bohr VA. (2014). Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell. 157(4), 882-96.