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Aged Related Degenerative Disease and Genome Instability

DZNE Lecture Award 2019 for Scientists

Date:25/11/2019, 17:00 - 18:00
Speaker: Prof. Fred H. Gage, The Salk Institute for Biological Studies, La Jolla, California
Location: CRTD, ground floor, auditorium
Host: Prof. Gerd Kempermann (DZNE/CRTD)

Abstract:

Humans are exceptionally long-lived in comparison to other primates, with a projected maximum lifespan of ~115 years. This extreme longevity presents unique challenges to many of the post-mitotic cells that compose our bodies and makes us highly susceptible to age-associated diseases (AADs) such as cancer, diabetes, and various neurodegenerative diseases.  In the first part of this presentation I will address the key features of aging that appear to drive neurodegeneration, compare the iPSC and direct conversion approaches for next-generation human cellular modeling, and discuss the extent to which iNs reflect aged neurons.

Human neurons contain high levels of somatic genomic variations that might derive from DNA double-strand break (DSB) intermediates. For the second part of my presentation, we applied high throughput genome-wide translocation sequencing to study replication stress-induced DSB hotspots, and identified replication-associated genomic fragile regions overlapping genes in neural progenitor cells (NPCs) derived from human pluripotent stem cells. Our results demonstrate that replication-associated genome instability may lead to neurological dysfunction by disrupting long neural genes linked to neurodevelopmental diseases.