Understanding and ameliorating ageing through the characterization of modulators of the p53 pathway

Evidence suggests that the increase with time of old cells plays a critical role in the deleterious effects that ageing has on organs and in the symptoms of many diseases, including cancer, fibrosis, diabetes and Alzheimer's. Preventing the accumulation of old cells substantially improves fitness and longevity in mice, proving that such therapies could have a clinical impact. If a similar strategy could be applied to humans, it could potentially ameliorate the pathologies that have been linked to old cell accumulation, thus increasing the quality of life and even extending the lifespan.
We have characterized several proteins involved in the process of cell ageing, including those that modulate p53, one of the master switches of the process. We will use this to obtain more information about the mechanisms involved in the ageing of cells, so we can better understand why and how it happens. Moreover, we propose to use take advantage of this information to design therapies that specifically target and kill old cells without affecting the normal ones. We will test this approach using several strategies, including nanotechnology. The compounds generated through this novel technique would be cost-effective, economic and easier to prepare than the antibodies and would have similar abilities. They could be used to quantitate the number of senescent cells in a tissue and to find better ways to kill them. Together, these approaches will allow us to better understand why cells age and to propose potential therapies that could eliminate old cells from the body and thus improve our health.