Investigating the impact of cellular senescence on muscle ageing
Sarcopenia – defined as the loss of muscle strength, mass and function with age – is a hallmark of ageing and frailty, and is one of the major causes of loss of independence and reduced quality of life in older people. Recent studies have shown that decline in muscle functionality occurs regardless of lifestyle, pointing to the mechanisms intrinsic to the biological process of ageing itself as the underlying cause, and to age(ing) as the biggest risk factor in the development of age-related musculoskeletal conditions. Cellular senescence has emerged as an important explanatory framework and contributor to age-related diseases. Several recent studies indicate that drugs targeting p16 positive senescent cells have great therapeutic potential in improving muscle physiology during ageing in mice. Thus, while it is clear that there is a link between senescence and age-related musculoskeletal decline, such studies have not robustly characterised the nature of senescence and the governing mechanisms in this organ, the cell types responsible for the induction of a senescent phenotype, nor the functional consequences of this phenotype with age. Furthermore, to date there are no investigations into the relationship between cellular senescence and muscle function in humans.
As such, the aims of my project are to robustly characterise the nature of cellular senescence in muscle ageing, determine the functional consequences of senescence in humans, and identify possible interventions to improve sarcopenia health outcomes in ageing populations. The long-term goal of the project is to build a more robust understanding of the role of senescence in muscle ageing with the hope of finding new targets for therapies capable of ameliorating sarcopenia’s functional and social burdens in old age.
- Robust characterisation of senescence with age and in relation to phenotypic presentation/data
- Investigating the effect of p16 +ve senescent cell clearance, using INKATTAC mouse model, on muscle function and health
- Investigating the role of cellular senescence in human muscle across the lifecourse via the groundbreaking MASS_Lifecourse study