Mechanisms and dose-response
Identify underlying mechanisms and dose-response relationships with risk markers for adverse health outcomes.
State of the science
Physiological adaptation to physical activity opposes many aspects of the pathophysiology of chronic diseases including that of type 2 diabetes, cardiovascular disease and the major cancers. However, the effects of acute and chronic physical activity on bodily organs, systems and processes vary substantially in relation to activity mode, frequency, intensity and duration.
Over the past 25 years, the mechanisms underlying the cardiometabolic benefits of regular Moderate to Physical Activity (MVPA) have been well characterised by us and others and provide a rationale and quantification for current physical activity guidelines for adults, children and youth. In contrast, reducing and breaking up sitting time is a new approach to enhancing daily physical movement and relatively little is known regarding the mechanisms of benefit.
In the absence of such evidence, public health guidelines for reducing sitting time and acceptable upper limits of accumulated or sustained sitting time will remain non-specific. Our team has made the first significant inroads regarding mechanisms — establishing that relative to uninterrupted sitting, breaks in sedentary time among adults acutely improves glycaemic control and reduces plasma fibrinogen.
Interestingly, we have shown that the gene expression pattern in vastus lateralis muscle associated with interrupted sitting has aspects which are both aligned with, and distinct from that of MVPA activity. This CRE will provide the platform to develop this work from laboratory studies examining the acute effects of breaks in sitting time over a single day to more meaningful and comprehensive mechanistic investigations of chronic change over weeks and months.
The use of simulated ‘real life’ settings (e.g. home, school and office) and the inclusion of younger and older age groups will ensure that study outcomes are relevant.
Proposed research in this theme
The next logical step in our research program is to conduct randomised controlled trials of activity breaks over periods of weeks to months and examine associated biological.
These studies will examine:
- A comprehensive suite of cardiometabolic endpoints to establish effects on:
- Interactions of breaking up prolonged sitting time with MVPA, dietary intake and meal patterns.
- Permutations in interrupting sitting (frequency, duration, intensity) to identify the most effective interventions.
- Risk factors (glycaemic control, blood pressure, lipids, coagulation, inflammatory markers).
- Hemodynamic mechanisms (autonomic function, circulating biomarkers, endothelial function, large artery biomechanical properties).
- Muscle adaptations (muscle gene / protein expression).
- Cognitive function (memory, learning and executive functions, time on task).
- Differential effects of age (from youth to elderly), gender (including menopausal status) and body mass index.
Establishing the dose-response relationships between interrupting sitting, risk markers and physiological adaptations will inform further work in specific disease groups — for example, among patients with hypertension, peripheral artery disease, osteoarthritis, overweight and obesity, the metabolic syndrome and diabetes, cognitive impairment and those with elevated thrombotic risk.
This CRE will provide a catalyst to focus the broad expertise of our team on the mechanisms underlying the benefit of breaking up sitting time. Theme chairs CI-D Dunstan and CI-G Kingwell have considerable experience in techniques to examine glycaemic control, lipid homeostasis, vascular function, hemostatic factors and muscle metabolism.
The involvement of CI-H Lambert and his laboratory provides a unique opportunity to further examine changes mediated by the autonomic nervous system, which is of particular relevance to the postural changes associated with interrupted sitting. This will be complemented by unique physiological expertise across the lifespan — specifically in children (AI Green, AI Chin A Paw), adults (AI Hamilton, AI Elisabeth Lambert) and older adults (AI Daly).
The CRE will facilitate the adaptation of the Baker Institute’s groundbreaking sitting time experimental models within Deakin University to permit experimental research into children in simulated school environments. Specifically, CIs Dunstan and Salmon together with AIs Green and Chin A Paw will focus on the impact of breaking up sitting time on physiological and cognitive function in children.
Deakin University have pledged a 3-year ‘value-add’ domestic PhD scholarship to facilitate this work. Similarly, CIs Dunstan, Owen, Kingwell and Lambert, in collaboration with AIs Daly and Hamilton, will develop and test strategies in simulated ‘aged-care’ environments in older adults, informing field-based work proposed by CIs Eakin and Healy.
The establishment of our new collaboration with AI Lautenschlager will extend applications and opportunities for our Fellows and PhD students into linking metabolic and neurotransmitter changes with indices of cognitive function.
The proposed investigations will capitalise on the Baker Institute’s recent investment and expertise in high throughput screening facilities allowing a discovery strategy using genomic, epigenetic and lipidomic approaches to identify candidate microRNAs, genes, proteins and regulatory pathways important in sedentary physiology. Such candidates may prove to be important risk markers for the efficacy of intervention strategies to reduce sitting time.
Building on our strong track record in intervention trials and integrative physiology, our CRE will characterise the mechanisms contributing to the health benefits of breaking up sedentary time across key age groups.
This is necessary to:
- Identify population groups likely to gain most benefit.
- Optimise the most effective permutations (frequency, duration, intensity) for interrupting sitting to inform public health strategy.