Savandara Besse

1 Introduction Brain ageing and related neurodegenerative diseases have dramatic consequences on quality of life and medical care costs. Dementia, one of the most prevalent manifestations of neurodegenerative disease, affects 23 million people in the UK alone at a cost of around £26 billion a year to the NHS (Collins et al. 2022; Panca et al. 2019; Wittenberg et al. 2019).

Abstract Decreased telomerase expression, telomere shortening, senescence-associated markers and inflammation have all been independently observed in the ageing brain and associated with disease. However, causality between limited telomerase expression and brain senescence and neuro-inflammation in the natural ageing setting is yet to be established.

Abstract Protein-protein interaction (PPI) networks accurately map environmental perturbations to their molecular consequences in cells, but effects of genome-wide genetic variation on PPIs remain unknown. We hypothesized that PPI networks integrate genetic and environmental effects, potentially defining biochemical mechanisms underlying complex polygenic traits.