Understanding and ameliorating ageing through the characterization of novel effectors of senescence.

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 symptoms of many diseases, including cancer, fibrosis, diabetes and Alzheimer's. Eliminating old cells as they accumulate 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 pathologies linked to old cell accumulation, increasing the quality of life and extend lifespan.
We have characterized a panel of new markers that allow us to selectively identify old cells using the senescent surfaceome (specific profile of surface epitopes of senescent cells). We will use this to obtain more information about the mechanisms involved in the ageing of cells, to better understand why and how it happens. Moreover, we propose to take advantage of this information to design therapies that specifically target and kill old cells without affecting normal ones. One approach is to obtain antibodies against these markers and attach them to a toxic compound. Previous research indicates that when such modified antibodies recognize and bind to their targets, the chemical is released and the cell is selectively eliminated. Cancer therapies based on this idea are already being used to successfully treat patients and we propose to apply the same idea to old cells.
We will also test a similar approach using nanotechnology. Compounds generated through this novel technique would be cost-effective, economic and easier to prepare than antibodies and have similar abilities. They could be used to quantitate the number of senescent cells in a tissue and find better ways to kill them. Finally we will use chemical inhibitors that block the cellular ageing process. These approaches will allow us to better understand why cells age and propose potential therapies that could eliminate old cells from the body, improving our health.