Understanding and ameliorating ageing through the characterization of novel markers of senescence
Lead Research Organisation:
University of Leicester
Department Name: Molecular and Cell Biology
Abstract
Evidence suggests that the accumulation of old, senescent cells plays a critical role in the deleterious effects of ageing, as well as the symptoms of many diseases. Clearance of these cells via caloric restriction shows improvements in fitness and longevity in mice, suggesting a clinical impact if a similar strategy could be applied to humans. It could halt or perhaps slow organismal decline, thus increasing the quality of life and even extending the healthspan.
It is also hypothesised that senescent cell accumulation has a role in diseases such as Cushing's. We plan to investigate the presence and role of these cells in this disease and investigate their clearance as a potential intervention to ameliorate impaired quality of life in patients in Cushing's remission.
Our lab, via a proteomic screening, has characterised several marker proteins involved in cellular senescence, including modulators of p53, one of the master switches of the process.
We believe caloric restriction will lead to a reduction of the effects of accumulated senescent cells and result in longer healthspan and/or improvements in Cushing's remission. Using the compounds identified in our screening as markers of senescence, success of caloric restriction in mouse models and human volunteers shall be validated using a proteomic approach, which will allow the quantification and validation of the network effects of this intervention.
We will test this approach using a multidisciplinary approach, including using nanocompounds generated in collaboration with the Piletsky lab. These can quantify the markers of senescence, demonstrating effectiveness of interventions, prior to proteomic analysis. Genomics data from other collaborators may give further insights into mechanisms of aging. Together, these approaches will allow us to better understand why cells age and to propose potential interventions or therapies that could eliminate old cells from the body and thus improve our health.
It is also hypothesised that senescent cell accumulation has a role in diseases such as Cushing's. We plan to investigate the presence and role of these cells in this disease and investigate their clearance as a potential intervention to ameliorate impaired quality of life in patients in Cushing's remission.
Our lab, via a proteomic screening, has characterised several marker proteins involved in cellular senescence, including modulators of p53, one of the master switches of the process.
We believe caloric restriction will lead to a reduction of the effects of accumulated senescent cells and result in longer healthspan and/or improvements in Cushing's remission. Using the compounds identified in our screening as markers of senescence, success of caloric restriction in mouse models and human volunteers shall be validated using a proteomic approach, which will allow the quantification and validation of the network effects of this intervention.
We will test this approach using a multidisciplinary approach, including using nanocompounds generated in collaboration with the Piletsky lab. These can quantify the markers of senescence, demonstrating effectiveness of interventions, prior to proteomic analysis. Genomics data from other collaborators may give further insights into mechanisms of aging. Together, these approaches will allow us to better understand why cells age and to propose potential interventions or therapies that could eliminate old cells from the body and thus improve our health.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M01116X/1 | 01/10/2015 | 31/03/2024 | |||
| 2264840 | Studentship | BB/M01116X/1 | 30/09/2019 | 30/09/2023 | Christian Clarke |