ICSIS · The interaction and clearance of senescent vascular cells by the innate immune system
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-06-01 → 2017-05-31
- EU contribution
- €183,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
The interaction and clearance of senescent vascular cells by the innate immune system
Very little is known about the mechanisms by which senescent cells interact with innate immune cells. Understanding how these processes work and how they may fail will be valuable for developing therapeutic interventions for boosting immune clearance of senescent cells. Such treatments could be used to treat or prevent a variety of different diseases. In doing so, such research will lead to improvements in healthcare interventions which will enable everyone to live healthier, longer lives. The overall objective of this study was to evaluate the impact of an early (acute) versus a late (chronic) senescent cell secretome on monocyte/macrophage function. It was suspected that if senescent cells were not killed by immune cells and persisted, their secretory phenotype would become altered (chronic) which could promote disease. Specific objectives included the assessment of (1) immunogenic factors on senescent cells, (2) the senescent secretome on markers of monocyte/macrophage activation/differentiation, (3) the impact of the senescent secretome on physiological responses by monocytes/macrophages including migration, adhesion and phagocytosis, and (4) the impact of a chronic senescent secretome on pathological responses by monocytes/macrophages. This research demonstrated that an acute senescent secretome promotes the differentiation of monocytes into anti-inflammatory M2-like macrophages associated with increased macrophage migration, adhesion and phagocytosis. However, a chronic senescent secretome promoted pathological features in monocytes/macrophages that has the potential to promote disease development.
Data: CORDIS, © European Union
Project objective
Cell senescence plays a paradoxical but important role in physiology; it protects organisms against cancer but also contributes to age-related loss of tissue function. Senescent cells accumulate during ageing, particularly at sites of age-related pathologies such as vascular tissue, contributing to fibrotic cardiovascular disease , . Therefore, the aim of this research is to understand why senescent cells accumulate later in life for the purpose of identifying potential therapeutic strategies for eliminating senescent cells. This project, founded in an emerging field of ageing research, will determine the interaction and clearance of senescent cells by ageing innate immune cells. Using in vitro, ex vivo and in vivo approaches the fellow will delineate the mechanisms of interaction between senescent vascular cells and the innate immune system and how they are impacted by age. This will significantly advance knowledge and lead to novel molecular targets to explore for eliminating age-associated vascular senescent cells. Since the field of cellular senescence is predominantly centred within molecular cell biology and cancer, this coordinated cross-disciplinary and cross-sectorial approach will provide novel insight into vascular senescence. Through an ambitious research training programme, the fellow will develop scientific, complementary and transferable skills in metabolism, innate immunity and vascular function in age-related disease from Aston, UK with intersectorial training to develop small molecule drugs from Redoxis SB, SWE; evaluate drug efficacy in models of ageing (Erasmus, NL); in the context of clinical cardiology (Aston/City Hospital, UK). It will deepen collaborations for partners, provide new techniques to the hosts and enhance the skills of exceptionally talented research fellow, with over ten years’ experience in the field of cellular senescence, forward as a research leader with experience of working effectively across sectors.
Original text from CORDIS.
Participants
- ASTON UNIVERSITY · BirminghamCoordinatorUnited Kingdom
Links
- View on CORDIS
- DOI: 10.3030/657286
- https://arquivo.pt/wayback/20211014225448/https://www.researchgate.net/project/The-interaction-and-clearance-of-senescent-vascular-cells-by-the-innate-immune-system
Data: CORDIS, © European Union