The Grillari LABS - Research Focus
One of the major challenges that modern medicine and biology are facing today is the continuously increasing life expectance of the population and in consequence the increase in age-related pathologies. Since the changes in physiology and morphology of organisms, tissues, and cells during their life span are still poorly understood, it is of vital importance to gain insight into the molecular mechanisms of aging and aging associated pathologies in order to design strategies that allow for maximizing the human health span.
Therefore, our focus of research at the University of Natural Resources and Life Sciences, Vienna (BOKU-VIBT) is on understanding the cellular and molecular changes that occur during aging, how these changes affect tissue functionality and on where and how repair and regeneration needs to counteract these changes.
Overview on how cellular senescence might contribute to aging of tissues and organisms.
(1) Cells are exposed to DNA damage, reactive oxygen species (ROS), high oncogenic signalling or to telomere shortening due to multiple replications. (2) If no repair or cell cycle arrest checkpoints are operative, cells might undergo immortalization and transformation as first steps of tumorigenesis or (3) cells might undergo cellular senescence or apoptosis. The senescent cells then (4) show an altered secretory phenotype and thus influence signalling, or (5a) they might be removed after undergoing senescence by apoptosis or by the immune system. This in turn (5b) leads to replication/transdifferentiation of neighbouring cells or of replication/differentiation of adult stem and progenitor cells, decreasing their proliferative potential. Finally, (6) the senescent cells display an altered behaviour and physiology in regard to their ‘daily’ tasks within a tissue. All this in turn leads to (7) changes in the microenvironment of tissues and to their functional decline, which in turn (8) enhances the risk of tumor development and (9) accelerates senescence, thus largely contributing to aging of organisms.