Normal cells loose the capacity to divide, and enter a postmitotic state called cellular senescence. This arrest is usually a response to DNA damage and genomic instability (including telomere uncapping).
It has become clear in recent years that this is not a ‘cell culture artefact’, but that cells senesce in the body during ageing. Senescence however, is much more than just the loss of replicative capacity, it is a major, stepwise reprogramming of main cellular functions, involving fundamental changes in secretory patterns, mitochondrial function, oxidant/antioxidant balance, protein homeostasis, and more.
We have extensively examined the role of oxidative stress for telomere-dependent senescence and its heterogeneity (Passos J et al. PLoS Biol 5 (2007) e110). Our main current interests are in the regulatory signalling networks governing the establishment and maintenance of the senescent phenotype, and the role of mitochondria in this processes.
Functionally, senescence is a completely different paracrine state, in which the release of senescence-associated secretory molecules, ROS and others might have a severe impact on their environment. We hypothesize that secretion of diverse bioactive substances from senescent cells can be causal for loss of tissue homeostasis in ageing.