Dean’s Seminar Series featuring Vilhelm Bohr, MD, PhD – “DNA damage and mitochondrial dysfunction in neurodegeneration and aging”

Dean’s Seminar Series

Vilhelm Bohr, MD, PhD
Chief, Section on DNA Repair
National Institute on Aging, NIH

Title & Abstract:

“DNA damage and mitochondrial dysfunction in neurodegeneration and aging”

We find that some DNA repair defective diseases with severe neurodegeneration have mitochondrial dysfunction.  Our studies involve cell lines, the worm (c.elegans), and mouse models and include the premature aging syndromes Xeroderma pigmentosum group A, Cockaynes syndrome, Ataxia telangiectasia and Werner syndrome.  It also includes models of Alzheimers Disease, which I will discuss. We find a pattern of hyperparylation, deficiency in the NAD⁺ and Sirtuin signaling and mitochondrial stress, deficient mitophagy.  We are pursuing mechanistic studies of this signaling and interventions at different steps to improve mitochondrial health and neurodegeneration.  I will discuss intervention studies in these disease models including a new Alzheimer mouse model using NAD supplementation.  NAD supplementation stimulates mitochondrial functions including mitophagy and stimulates DNA repair pathways.  Based on human postmortem material and IPSC cells we identify mitophagy defects as a prominent feature in Alzheimers disease (AD). Using c.elegans AD models we screened for mitophagy stimulators and identified compounds that subsequentially also show major improvement of AD features in mouse models. We are exploring senescence and cGAS-STING signaling pathways, which will be discussed.

***CME/CE Credit is being offered for this Seminar***