Grant: Fellowship: Prize of Excellence in Research on Aging

Telomeres are specialized structures at the ends of our chromosomes. Telomere length has long been believed to limit the number of times a cell can divide in our bodies, thereby representing a major regulator of the aging process. The Karlseder laboratory has recently discovered that the role of the telomere in controlling aging is much more complex. Despite decades of research, no organized pattern of telomere distribution has been discovered in human cells up to now. Using state of the art microscopy, they found a specific enrichment of telomeres at the nuclear periphery during a short time window at the end of the cell division process. Furthermore, this localization changes with age and is much less pronounced in old cells. This discovery is of profound importance for cellular organization, gene expression patterns and chromosome function. Based on this breakthrough, I am suggesting the new hypothesis that telomere localization directly affects chromosome organization, and in turn regulates genome-wide gene expression programs that could alter cell fate during aging, cellular responses to external and internal stress, as well as age-associated disease. It has long been suggested that the onset of many age-associated diseases, such as progeria, Alzheimer's, cardiovascular disease, neurodegeneration, metabolism dysfunction, cataracts and inflammation is coordinated. I am now suggesting that telomere localization and the resulting changes in cellular gene expression programs could be the driver of this coordination, representing a unifying explanation for aging and age-associated diseases. I expect to learn from these experiments how telomere-driven changes in chromosome localization affect gene expression programs during aging, how this drives the onset of age-associated disease and most importantly, how age-associated diseases are linked to each other and whether their cumulative onset can be suppressed by keeping telomere localization in a youthful state.