Alsaleh Group | Ageing in the musculoskeletal system and beyond earth

Ageing Beyond earth 

Population ageing is becoming one of the most significant social transformations of this century. It impacts different sectors of society including labor force and financial resources. Ageing is characterized by a progressive loss of cellular function, and is associated with various diseases including neurodegeneration, cancer, cardiovascular disorders, and infection. In consequence, the increased ageing population not only impact the quality of life but also comes with a high medical-economic cost, which is frequently underestimated.

Though, the ageing research has made significant progress over recent years, a considerable amount of work should be carried out to better understand ageing at the molecular, cellular, and organismal level to improve healthy lifespan.

A notable observation is that the unique environment of space results in changes in various aspects of astronauts' bodies, such as bone density, muscle mass, and cardiovascular function.  Indeed, microgravity can be considered as an accelerating ageing model and provided an excellent platform to investigate ageing mechanism that normally occur over a very long period in earth. However, due to limited access and collaboration between lab 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, Dr Ghada Alsaleh has the opportunity to foster interdisciplinary collaboration aimed at advancing cellular and molecular biology research in space to enhance our understanding of human physiology and human health on Earth. 

Overview

Ageing research has made significant progress over recent years, highlighting 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. These molecules have safety issue, which limit their use and make it essential to discover safer and more effective drugs. Recently, we found that a pathway controlling autophagy, called the TFEB pathway, is often dysregulated in age and crucial for the prevention of cellular ageing. Re-establishing TFEB expression in aged cells through therapeutic approaches can restore cellular functions and rejuvenate the cells. In our lab, we aim is to develop a drug enhancing the TFEB pathway to allieviate age-related molecular dysfunctions. This approach may hold the key to improve a broad range of age-associated morbidities and promote a 'healthier' aging.

Aims

Our overall aim is to identify the contribution of the age-related TFEB pathway to the development and progression of osteoarthritis and to use this knowledge to develop new treatments for OA.