Alignment of exercise timing with intrinsic circadian clocks for intervertebral disc health and matrix homeostasis

Among the many health challenges associated with ageing, degeneration of the soft tissue intervertebral discs (IVDs) in the spine is a primary feature of the ageing skeleton, contributing to pain and loss of mobility. However, we do not fully understand why age increases susceptibility to disc degeneration. The IVD separates our bony vertebraes and provides important cushioning and load-absorbing functions during regular daily cycles of activities.

Recently, our group discovered functional 24-hour internal clocks in the IVD. This body clock becomes weakened and imprecise with age and its disruption through clock gene deletion leads to tissue damage and loss of characteristics of human IVD. This project aims to understand how our body clocks in the spine are regulated on a daily basis and why they weaken with age.

We will establish how daily mechanical loading patterns of the spine due to physical activity keep the IVD clocks in synchrony with the rhythmic environment. We will also assess the importance of timing of exercise on spine health. Specifically, we will use a novel IVD "clockless" mouse model, treadmill exercise and cultures of cells and tissues to address the following questions: 1) Is the clock in the signalling centre of the IVD important for tissue health? 2) Do IVDs respond differently to mechanical loading depending on the time-of-day? 3) How mechanical loading keeps the IVD body clocks aligned with the external day/night cycle?

This research builds on our recent novel discoveries and holds strong potential to advance our understanding of IVD circadian biology and promote tissue health against ageing. As such, there is an enormous potential for improving health and quality of life throughout our life course. Moreover, our findings emphasize the importance of exercise timing for better skeletal health, which will have a long-lasting impact on the health and well-being of the nation.

This is particularly important because the greying of the population and the ever-increasing demands of our modern 24/7 society frequently disrupt our body clocks which can adversely impact on our health, wellbeing and productivity.