Neural and muscular mechanisms of age- and sex-related impairments in muscle function and fatigue in old and very old adults

Even in the absence of disease, ageing leads to impairments in muscle function, limiting the abilities of many older adults to perform daily activities, such as walking. These functional declines are due to ageing-related impairments in the brain, spinal cord, and muscles. However, these declines in function are poorly understood in adults over 80 years of age, which is especially true for older females, as these groups are typically omitted from human physiology research.

To improve our understanding of ageing-related changes in muscle function, we will evaluate brain, spinal cord, and muscle function during force or power production and compare differences among young (18-30 years), old (60-69 years), and very old (over 80 years) females and males. The inclusion of very old adults is critical, as these individuals are most susceptible to impairments in muscle function. Furthermore, we are focusing our efforts on the thigh muscles, as they are vital for daily activities and mobility, and are greatly impacted by advancing age. This project will provide foundational knowledge to guide the development of interventions, such as age- and sex-specific exercise prescriptions, to restore muscle function and quality of life for older adults.

Anti-inflammatory cytokine function in individuals with type 2 diabetes: Impact of hyperglycemia and the restorative effects of exercise

Chronic low-grade inflammation (i.e. the persistent low-level production of pro-inflammatory factors by immune cells) is a major contributor to the development and progression of type 2 diabetes (T2D). We have recently demonstrated that cells from individuals with T2D also have impaired anti-inflammatory responses — a defect that appears to be driven by hyperglycemia. Despite these novel observations, the relationship between hyperglycemia and impaired anti-inflammatory responses (and the underlying mechanisms) across individuals with varying levels of glycemic control has not been examined. Moreover, the ability of a lifestyle intervention to restore anti-inflammatory responses via normalization of blood glucose levels in individuals with T2D has not been evaluated. As such, we aim to: 1) determine whether a dose-response relationship exists between the level of hyperglycemia and magnitude of impairment in anti-inflammatory responses across individuals with varying levels of glycemic control, 2) explore the mechanisms linking hyperglycemia to impaired anti-inflammatory responses, and 3) evaluate the efficacy of a daily post-meal walking intervention to restore anti-inflammatory responses in individuals with T2D.

Let’s ride! Supporting individuals at risk of type 2 diabetes who self-identify as an ethnic minority in a community-based diabetes prevention program using electrically assisted bicycles

Interventions to prevent the progression of prediabetes to type 2 diabetes (T2D) are needed. This need is greater among individuals self-identifying as an ethnic minority in Canada, because they are at greater risk for developing T2D and at a younger age than individuals of European descent. While there is strong evidence that physical activity (PA) can reduce diabetes progression, adherence to PA is poor following diabetes prevention programs. Compounding this problem, diabetes prevention programs are failing to reach ethnically diverse populations. Alternative methods of promoting PA that is appealing to ethnoculturally diverse populations is needed. Electrically assisted cycling is an activity that can lead to positive health outcomes. E-bikes enable people to exercise outside and may reduce barriers of access to, and cultural resistance to joining, an exercise facility. This research will examine the effectiveness of using e-bikes as a method of increasing PA among individuals identifying as an ethnic minority who are at risk of developing T2D in interior BC. This research will provide information on a new, alternative form of promoting PA as part of a diabetes prevention program that can be used to tailor existing programs.

The effect of temperature on brain bioenergetic stress in hypoxia

Cooling the brain is a therapeutic strategy to protect it from stress. The long-held belief is that cooling the brain reduces its activity — and thus its need for oxygen — thereby tilting a favourable balance of oxygen supply and demand. However, recent data from our lab challenges this paradigm. We have shown that brain blood flow is reduced by whole-body cooling, and this dramatically impairs oxygen supply to the brain. Therefore, it is important to know exactly how much the brain’s activity is reduced so that we can determine whether the balance of oxygen supply and demand is improved or further disrupted. Surprisingly, this is unknown in the human brain. Our objective is determine how the brain’s oxygen supply and demand is affected by cooling and heating, and how this impacts its resilience to stress. We will heat and cool healthy human subjects and expose them to low oxygen, whilst measuring markers of brain stress. We will then collect the same markers of brain stress in patients with brain injury before, during and after therapeutic cooling. Together, these studies will expose how temperature affects the brain’s resilience to stress and provide rationale for how best to harness the cold to protect the brain.

The ADAPT Project: Adaptation, Development, and Positive Trajectories in the context of childhood adversity

Over half of Canadians have experienced at least one childhood adversity (CA), which is linked to an increased risk of poor health and wellbeing across the lifespan. Current approaches have focused on linking CA to poor outcomes, yet this approach overstates the impact of risk and devalues the importance of protective factors enabling individuals to withstand, adapt, and recover. The focus on outcomes may also fail to capture the trajectories of wellbeing and cyclical nature of resilience and vulnerability.

This program of research utilizes a mixed-methods approach to explore pathways to wellbeing in the context of CA, focusing on the timing and type of protective factors. To fully understand how socio-environmental and biological factors contribute to health and wellbeing inequity due to CA, we must examine the pathways to impairment and wellbeing using a developmentally informed framework. Changing the question from ‘how are youth at risk’ to ‘how do youth adapt,’ and shifting to a model where those with trauma histories are not defined by their risk. Findings will produce actionable evidence for practitioners and policymakers to develop early intervention and prevention programs fostering health equity for those with CA.

Systems transformation for health equity: The PHAIRNESS Research Program

There are growing differences in health among population groups due to unfair social conditions that disadvantage some people more than others in British Columbia and beyond. Health systems play a role in holding this problem in place by presenting unnecessary barriers to accessing quality healthcare. Health systems also have a key role in closing these gaps by taking action to change the underlying conditions that shape health and wellbeing. The Population Health Approaches to Implementing Research (k)Nowledge for Equitable Systems & Strategies (PHAIRNESS) Research Program aims to make visible and intervene on systems-level problems in three connected systems: health systems, surveillance systems and research systems. By working closely with health systems, communities and people who are impacted by these issues, research findings will be relevant, useful, and ready to be rapidly applied to improve health systems and support the wellbeing of all people in British Columbia.

Evolutionary mismatch: a cause of cardiovascular disease in industrialized societies?

In the Origin of Species, Charles Darwin presented that species evolved to best suit their environments. Endurance exercise was central to the extensive hunting and gathering of early human ancestors. To support prolonged exercise in the heat, the cardiovascular system must work hard to keep the body cool and to provide blood to exercising muscles and the brain. Thus, having a cardiovascular system that supports endurance activity in the heat would have been beneficial to early humans. In stark contrast, humans in postindustrialized societies live in temperature-controlled, sedentary environments. Cardiovascular disease is the leading cause of death worldwide; however, it is extremely rare in preindustrialized societies, such as modern hunter-gatherer and subsistence farming populations. This project aims to investigate cardiovascular aging from an evolutionary lens. Over the next three years, we will compare vascular structure and function in semi-wild chimpanzees, hunter gatherers in Tanzania, subsistence farmers in Mexico, and sedentary residents of British Columbia. The results will help us to understand what normal cardiovascular aging in humans is.

Understanding counsellor-client interactions in spinal cord injury exercise counselling: a novel method to explain outcomes of randomized controlled trials by assessing intervention fidelity

Behavioural interventions often consist of conversations between counsellors and clients and can be a successful way to promote a healthy lifestyle. However, controlled intervention outcomes are not always successfully translated to real-world settings. A possible reason for this poor translation, is that researchers do not use information on how counsellors and clients interact with each other to explain intervention outcomes. Recently, a new method, called state space grids, has been developed to study and visualize how a counsellor and client interact with each other over time. This study will use state space grid methods to study conversations about health-enhancing exercise between counsellors and clients with spinal cord injury (SCI) to explain health outcomes. Participants receive tailored exercise counselling. Recordings of the sessions will be analysed using state space grids. The findings will help us to better study and understand how, when and why counselling is successful in changing health behaviour. These new insights can be used to develop training guides for counsellors and improve exercise counselling. In turn, understanding and improving effective exercise counselling will enhance lives of many people with SCI.

A novel strategy to mitigate secondary hypoxic injury following traumatic spinal cord injury through the augmentation of local microvascular oxygen supply

There are approximately 2000 new cases of traumatic spinal cord injury (SCI) per year in Canada, with an associated health care cost of more than $1,500,000 per patient over a lifetime. The severity of SCI is compounded by injury processes that arise following initial trauma, which are related to a reduced oxygen supply to the injured spinal cord tissue. This process, where oxygen supply is reduced, is modifiable and therefore an ideal target for treatments aiming to improve outcome in SCI patients. Despite the potential to improve oxygen supply to the injured spinal cord, current treatments have yet to demonstrate notable efficacy. This is because it is difficult to alter oxygen supply to the spinal cord without causing undesirable changes in a patient’s blood pressure. We will utilize novel breathing strategies to target a specialized blood flow control mechanism to improve oxygen delivery to the injured spinal cord in rodent models of SCI. Further, we will characterize the function of this blood flow control mechanism in SCI patients, which will allow us to establish the potential efficacy of an exciting new avenue for improving outcomes and reducing healthcare burden after SCI.

Plant based anticancer drugs – from discovery to final products

Plants are endowed with biological catalysts (enzymes) that make natural drugs used to treat various human illnesses. Among these, the Chinese happy tree (Camptotheca acuminata) produces the anticancer drug camptothecin. Although camptothecin is readily convertible to the more potent drugs topotecan (Hycamtin) and irinotecan (Camptosar), this requires chemical synthesis steps which rely on toxic chemicals and petroleum-based resources.

Our research program aims at developing  multidisciplinary approaches to discover and modify happy tree’s enzymes that facilitate the production topotecan, irinotecan and new camptothecin-derived analogues. We aim to rapidly generate 25-50 camptothecin-derived analogues by biotechnological means and test these compounds using in vitro and cellular assays to assess potential anti-cancer activity.

Our biosynthetic approach will allow us to explore the untapped medicinal potentials of a whole host of novel camptothecin-related chemicals in addition to topotecan and irinotecan. Long-term efforts, also ongoing in our laboratory, will focus on synthetic biology approaches to scale up production of compounds that show promising bioactivity.