Tom Kirkwood - VPH2014
Untangling the complexity of ageing
Untangling the complexity of ageing
Professor Tom Kirkwood
Newcastle University
Abstract
The ageing physiome and its relationships to health and disease are extraordinarily complex, yet it is of great importance that we should understand these connections in order to develop targeted approaches to improving health and quality of life in a world where life expectancy is rapidly increasing. A longstanding barrier to progress in ageing research has been the coexistence of multiple, seemingly competing hypotheses about causal mechanisms. Each mechanism tends to be partially supported by data indicating that it has a role in the overall cellular and molecular pathways underlying the ageing process. However, the magnitude of each of these individual contributions is usually modest. The development of virtual models of the physiological mechanisms of ageing is likely to be essential in untangling the inherent complexities of these mechanisms and their interactions. The success of virtual, systems-biology approaches in unraveling the complexity of ageing can be seen in recent studies on cell replicative senescence, which show that the entry of cells into senescence and the maintenance of the senescent state are regulated by a feedback cycle involving DNA damage to telomeres as well as non-telomeric parts of the chromosomes, mitochondrial dysfunction and signaling via reactive oxygen species. An important challenge also exists in connecting the network of (random) damage-driven proximate mechanisms of ageing with the higher level (genetically specified) signalling pathways that influence longevity. Ultimately, one of the greatest challenges in developing and deploying the science of the virtual physiological human will be to address what it means to virtually grow old.