Alsaleh Group | Ageing in the musculoskeletal system and beyond earth

Ageing in the population

Population ageing is becoming one of the most significant social transformations of this century leading to medical and social disability. Ageing is characterised by a progressive loss of cellular function, and is associated with various diseases including neurodegeneration, cancer, cardiovascular disorders, musculoskeletal diseases (e.g. osteoarthritis), and increased infection susceptibility (called immunosenescence).  Though ageing research has made significant progress over recent years, considerable work is needed to understand better ageing at the molecular, cellular, and organismal levels, to improve healthy lifespan. 

Targeting autophagy

Many groups, including ours, have identified several hallmarks that are considered to contribute to the ageing process. Autophagy, a process of cellular recycling, is implicated in most of these ageing hallmarks. Autophagy declines with age and induction of autophagy has been shown to improve age-associated changes. This makes autophagy a promising therapeutic target. Unfortunately, there are only a handful of autophagy-inducing-drugs that have been shown to reverse ageing. Since these molecules have safety issues, it is essential to discover safer and more effective drugs. Recently, we found that the TFEB pathway, which controls autophagy, is often dysregulated in age, and is crucial for the prevention of cellular ageing. Re-establishing TFEB expression in aged cells through therapeutic approaches can rejuvenate cellular functions. In our lab, we aim to understand TFEB regulation with age, and to identify drugs that enhance both TFEB and other autophagy pathways. In this way, we hope to alleviate the molecular dysfunctions that occur in the ageing of the musculoskeletal and immune systems, both of which rely on autophagy.

Ageing beyond earth

A notable observation is that the unique environment of space results in changes in various aspects of astronauts' bodies, such as decreased bone density, muscle mass, and cardiovascular function. Microgravity can therefore be considered as an accelerating ageing platform that can be used to investigate ageing mechanisms that normally occur over a long period on earth. However, due to limited access and collaboration between labs in earth and space, there has been relatively little research conducted on how space travel impacts the ageing process. Through the UK's first Space Innovation Lab at the Botnar Institute for Musculoskeletal Sciences, our group is fostering interdisciplinary collaboration aimed at advancing cellular and molecular biology research in space. In this way, we aim to understand human physiology and improve human health on Earth.