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The Department of Biomedicine

BBB seminar: Vilhelm A. Bohr

DNA damage signaling to mitochondrial dysfunction in neurodegeneration and aging

Vilhelm A. Bohr
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA

We find that some DNA repair defective diseases with severe neurodegeneration have mitochondrial dysfunction. Our studies involve cell lines, worm (C. elegans) and mouse models and include the premature aging syndromes Xeroderma pigmentosum group A, Cockaynes syndrome, Ataxia telangiectasia (AT) and Werner syndrome. We find a pattern of hyperparylation, deficiency in the NAD+ and sirtuin signaling and mitochondrial stress. 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. In AT cells, mice and nematode worms, base excision repair is stimulated by NAD supplementation. This also happens in an Alzheimer’s mouse deficient in DNA polymerase ß, and this will be discussed. DNA Polß affects mitochondrial functions via its nuclear role, and via a newly identified role in mitochondrial DNA repair.

Chairperson: Mathias Ziegler, Department of Biomedicine