Björn Schumacher1

1 Institute for Genome Stability in Aging and Disease, Medical Faculty, Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD) Research Centre and Centre for Molecular Medicine (CMMC), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany

Aging is the biggest risk factor for chronic diseases ranging from dementia to cancer. Prevention of age-related diseases is a prerequisite for healthy aging and requires an understanding of the mechanisms of the aging process. The nuclear DNA cannot be replaced and is hence critically dependent on constant DNA repair. Defects in DNA repair such as nucleotide excision repair can accelerate aging in humans and give rise to a wide spectrum of age-related pathologies during childhood. To better understand the intricate role of genome stability in the aging process, we investigated the consequences of chronic DNA damage in the nematode C. elegans. This in vivo model enabled us to investigate the distinct genome stability mechanisms in terminally differentiated and thus irreplaceable somatic cell such as neurons and immortal germ cells that indefinitely perpetuate the genetic information. In addition, we identified systemic DNA damage response mechanisms that operate between the germline and somatic tissues. We found that the genome quality control in germ cells is influenced by somatic stress responses, which could integrate germline signals with environmental influences. We employed the nematode as discovery tool to identify the first master regulator of somatic DNA repair, which might provide novel geroprotective therapeutic strategies for human longevity. Longevity itself might be determined by the accumulation of stochastically occurring damage as indicated by our ability to predict biological age purely based on the amount of accumulated stochastic variation in biological parameters. Deeper insight into the mechanisms of genome maintenance will provide the basis for a better mechanistic understanding of the organism’s aging process and new perspectives for healthy human aging.