The Role of Ageing and Parenchymal Senescence on Macrophage Function and Fibrosis
Ross A Campbell1, Marie-Helena Docherty1,2, David A Ferenbach1,2
1Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Abstract:
In this review, we examine senescent cells and the overlap between the direct biological impact of senescence and the indirect impact senescence has via its effects on other cell types, particularly the macrophage. The canonical roles of macrophages in cell clearance and in other physiological functions are discussed with reference to their functions in diseases of the kidney and other organs. We also explore the translational potential of different approaches based around the macrophage in future interventions to target senescent cells, with the goal of preventing or reversing pathologies driven or contributed to in part by senescent cell load in vivo.
Insights
This review explores how senescent cells impact health directly and indirectly through macrophages. Targeting macrophages offers potential therapies for age-related diseases driven by cellular senescence.
Area of Science:
- Cellular biology
- Immunology
- Gerontology
Background:
- Cellular senescence is a state of irreversible cell cycle arrest.
- Senescent cells accumulate with age and contribute to various pathologies.
- Macrophages play critical roles in tissue homeostasis and disease.
Purpose of the Study:
- To review the direct and indirect biological impacts of cellular senescence.
- To examine the interplay between senescent cells and macrophages.
- To explore macrophage-based therapeutic strategies targeting senescence.
Main Methods:
- Literature review of senescence and macrophage biology.
- Analysis of the role of macrophages in senescence-associated diseases.
- Exploration of translational approaches targeting senescent cells via macrophages.
Main Results:
- Senescence has both direct cellular effects and indirect effects mediated by immune cells.
- Macrophages are key players in clearing senescent cells and modulating inflammation.
- Dysfunctional macrophages can exacerbate senescence-driven pathologies.
Conclusions:
- Understanding the senescence-macrophage axis is crucial for developing new therapies.
- Targeting macrophages presents a promising strategy to mitigate senescence-related diseases.
- Future interventions may leverage macrophages to clear senescent cells and restore tissue function.
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