from Institute for Genome Stability in Aging and Disease, Research Centre and Centre for Molecular Medicine (CMMC), University of Cologne,  Germany

 will give a seminar entitled

Genome Stability in Aging and Disease: New Perspectives from C. elegans

Aging is an inherent property of somatic tissues. In contrast, germ cells indefinitely perpetuate the genetic information. According to the disposable soma theory, selective pressure has shaped maintenance and repair mechanisms that ensure somatic functioning early in life, while the soma may decay upon successful reproduction. We focus on three central questions: (1) How is somatic maintenance adapted to the requirements of the germline, (2) which processes determine somatic maintenance and thus control aging, and (3) what are the underlying mechanisms for germ cell immortality?

The causal contribution of DNA damage not only to cancer development but evenly to the aging process has been demonstrated by progeroid (premature ageing-like) syndromes that are caused by mutations in DNA repair genes. We have established the nematode C. elegans as metazoan model to investigate the consequences of DNA repair defects that in humans cause either cancer predisposition or developmental retardation and premature aging.

Using this model we identified germline DNA damage induced systemic stress resistance (GDISR) that adapts somatic maintenance to genomic impediments of germ cells. We postulate that by elevating somatic endurance, GDISR extends reproductive lifespan to allow germ cells to repair their genomes and resume offspring generation later in life.

Moreover, we determined that while DNA repair mechanisms counteract the accumulation of DNA damage during the lifespan, longevity assurance mechanisms such as the FOXO transcription factor DAF-16 elevate DNA damage tolerance thus promoting longevity amid accumulation of damage.

To ensure the immortality of germ cells, genome stability in primordial germ cells (PGCs) is a prerequisite. We have determined that the DNA damage response in PGCs is regulated non-cell-autonomously through the adjacent somatic niche cells. Our data suggest that the somatic niche regulates the maintenance of heritable genomes by impacting the DDR in PGCs.