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Somatic mutation patterns in the genome of healthy human cells: new insight into the mechanisms of aging

1 Oct 19

Speaker: Irene Franco, Ph.D. Dept. of Biosciences and Nutrition. Karolinska Institute. Stockholm. Sweden



Organizers: IRB Barcelona
Date: Tuesday 1 October, 12.00h
Place: Felix Serratosa Hall, Parc Cientific de Barcelona

Host: Fran Supek, PhD - IRB Barcelona


Somatic mutations that accumulate in the genome of every cell contribute to aging and age-related diseases, but our understanding of the causes and consequences of somatic mutagenesis in healthy human tissues is still limited. We present a comprehensive study of the somatic mutations occurring in multiple, healthy tissues, including kidney, skeletal muscle, fat and epidermis. Our whole genome sequencing data, obtained by single cells clonally expanded in vitro, allowed us to analyze patterns of somatic mutation types and distribution and their variation across different tissues and age groups. These data lead us to the identification of a “basal mutagenesis” occurring in every tissue and cell type. DNA repair effectively counteracts basal mutagenesis, but a general decline is observed with aging and leads to mutations in gene-rich regions. In agreement with a functional impact of these mutations, single clones of skeletal muscle stem cells from aged individuals show an association between high mutation burden and reduced proliferative capacity. We also found a unique pattern of mutation distribution in a tumor-prone kidney cell type, the proximal tubule epithelial cells. Mutations are enriched in transcribed genes and regulatory regions, enhancing the chances of acquiring a cancer driver mutation. All together, our findings support somatic mutagenesis as a key factor in the functional decline and propensity to cancer observed with aging.

Extraordinary Seminar