Exploring conserved gene expression programmes across tissues in ageing
Principal Investigator: Dr Gary Reynolds
There have been dramatic increases in life expectancy in the UK and these changes are predicted to continue with around 8.6 million people in 50 years time. A key goal of ageing research is to ensure that longer life is not disrupted by ill-health and disability.
We all experience ageing differently and chronological age does not always reflect this. We would like to develop better measures of biological ageing with the aim of improving approaches to prevention, diagnosis and treatment. The MASS_Lifecourse study, designed in collaboration with members of the public and patients, is currently recruiting participants who will be invited to donate a small biopsy of muscle tissue. We hope that the data from this study will help us predict those individuals who would benefit from interventions to prevent and treat age-related muscle loss, or Sarcopenia. We are focussing on muscle because it acts as a window into broader ageing. It has been recognised as an important health problem because it is common in older adults and associated with decline in physical function as well as a reduced quality of life. Sarcopenia can also lead to serious health consequences in terms of increased disability, illness and the need for increased health and social care.
In this pilot work we would like to extend the MASS_Lifecourse study to simultaneously sample a small piece of skin and subcutaneous fat at the same time as the muscle biopsy. Because an incision is required as part of the muscle biopsy, this will not change the risk profile of the procedure but may give us important additional information.
We would like to investigate whether a skin biopsy, which is a simple and low-risk procedure, is capable of giving us the same information as a muscle biopsy and potentially be used as a measure of biological ageing in general in future.
Aims
- Define gene expression and cell type compositional changes with respect to age across a range of healthy human tissues and cell types
- To assess the feasibility and acceptability of incorporating punch biopsy of overlying skin and fat as part of biopsy of the vastus lateralis muscle using a Weil-Blakesley conchotome
Project milestones
- Ethical approval for modification of MASS_Lifecourse study to incorporate combined skin, fat and muscle biopsies
- Sample collection of combined skin, fat and muscle biopsies as part of MASS_Lifecourse study
- Literature review and integration of human scRNAseq datasets from healthy tissue with required metadata
- Development of multivariate gene expression models to explore effects of ageing across cell types and tissues
- Functional annotation of gene expression modules and validation in additional datasets, including bulk RNAseq