Fontana healthy longevity research group

Each year billions of dollars are spent world-wide to treat highly prevalent chronic diseases, which are largely preventable with the implementation of the best healthy lifestyle practices.

Our research program at the Charles Perkins Centre and Royal Prince Alfred Hospital provides a powerful new medical approach for the prevention and treatment of multiple age-related diseases that share a common metabolic substrate. This new approach is based on growing evidence from the biology of ageing field showing that targeting well-characterised metabolic and molecular pathways can inhibit the accumulation of cellular and tissue damage, and dramatically extend healthspan and influence the clinical progression of multiple chronic conditions.

We concentrate on elucidating how specific nutrition and exercise interventions, by acting on different but complementary pathways, can modulate the pathogenesis and prognosis of 4 disease groups: abdominal obesity/metabolic syndrome, cancer, cardiovascular disease (CVD), and dementia. Our primary objectives are to:

• apply state-of-the-art whole-body physiological and tissue-specific molecular techniques to well-designed RCTs to evaluate the clinical, metabolic, and molecular effects of specific nutrition and exercise interventions on 4 thematic clinical outcomes – abdominal obesity/metabolic syndrome, cancer, cardiovascular disease, and cognitive decline ‒ and to establish the interconnections between these groups of diseases
• develop a meta-phenotypic map across multiple scales of responses to nutrition, including multi-omics (transcriptome, methylome, metabolome, proteome/phosphoproteome, microbiome), cardiometabolic and cognitive variables and inflammatory factors
• determine how the microbiome (and the resulting metabolic adaptations) respond to nutritional and exercise challenges
• develop predictive models using systems biology and machine learning computational biology to understand and manage the relationship between energy intake, macronutrients, micronutrients, physiological responses, health and age-associated diseases.

A randomised controlled trial evaluating the effect of an intensive lifestyle intervention for reversal of coronary heart disease (the LIVEPLUS Trial):

• This randomized clinical trial sets out to assess the effects of conventional standard of care treatment compared to a 12-month intensive lifestyle program on people with a CT-diagnosis of coronary heart disease.

A phase 2 randomized clinical trial evaluating the effects of a short-term ketogenic diet combined with 24-hour fasting before and during chemotherapy in patients with acute myeloid leukaemia:

• The man aim of this study is to develop dietary regimens to protect cancer patients against the damage of chemotherapy. This will transform clinical oncology management and generate commercially valuable intellectual property as these interventions become standard of care for chemotherapy regimens in haematological malignancies and solid tumours.

Development of a meta-phenotypic map across multiple scales of responses to nutrition, including multi-omics (transcriptome, methylome, metabolome, proteome, microbiome), cardiometabolic, hormonal and inflammatory factors:

• Large amounts of clinical, metabolic and molecular (-omic) data have been generated by my research group in previous human studies of the effects of calorie restriction, intermittent and prolonged fasting, protein restriction and Mediterranean diet with and without weight loss. We are developing predictive models using systems biology and machine learning computational biology to understand and manage the relationship between energy intake, macronutrients, micronutrients, physiological responses, health and age-associated diseases.

Development of an e-Health platform on smart devices to educate and coach patients through the three pillars of a healthy lifestyle (diet, exercise and mental stress):

• This e-health platform allows patients to engage in special small unit-based learning, called "micro-learning", which assumes that the learning tasks can be fragmented but connected, and allows learners to easily participate in educational activities regardless of restrictions in time and location. The e-health platform also incorporates validated design features to enhance patients' perceived 'co-presence' with the clinicians virtually, so as to reduce their anxiety and improve their confidence during the intervention. We are currently testing to use of this digital intervention with the aim to design an effective model of care to reduce metabolic risk factors implicated in the pathogenesis of many chronic diseases that share a common metabolic and molecular substrate. 

The aim of this research program is to develop a new mechanism-based way of preventing and treating age-related diseases, while compressing the period of intense morbidity in later years through biomedical discovery and health service innovation. New scientific knowledge of the shared metabolic substrate amongst multiple common chronic diseases will be generated through the comprehensive investigation of how a combination of specific nutritional and lifestyle interventions influence their progression. This will provide a new framework for allowing clinicians and individuals to optimize nutrition and exercise for specific health outcomes and for the prevention and management of lifestyle-related diseases that are epidemic in modern society.

• NHMRC Investigator Grant, $3.4 million, 2019: Food and exercise as medicine: a new medical approach for the prevention of age-related diseases.
• Australian Youth and Health Foundation, $2.5 million 2019: Effects of comprehensive lifestyle modification on atherosclerosis progression in patients with coronary artery disease measured by non-invasive CT coronary angiography.

• Dr Sophie Cassidy
• Dr Cynthia Kroeger
• Mr Sayan Mitra (PhD candidate)