• Medicina Regenerativa

[CMR[B] Lecture] Promoting Health and Longevity through Diet: Metabolic and Molecular Mechanisms

Luigi Fontana, MD, PhD

Professor of Medicine and Nutrition

Leonard P. Ullman Chair in Translational Metabolic Health

Director, Healthy Longevity Research and Clinical Program

Charles Perkins Centre - Central Clinical School

Faculty of Medicine and Health, University of Sydney, Australia




Trillions of dollars are spent every year to treat highly prevalent chronic diseases that are largely preventable. Modern medicine focuses on diagnosing and treating clinically evident diseases one at the time, mainly with drugs and surgery. The problem of this approach is that many age-related chronic diseases begin early in life and progress over decades of unhealthy lifestyles, which trigger a wide range of metabolic and molecular alterations deeply influencing the initiation, progression and prognosis of multiple medical conditions.

Evidence from experimental studies indicates that the age-associated accumulation of molecular damage can be prevented or greatly delayed by dietary, genetic and pharmacological manipulations that downregulate key cellular nutrient-sensing and inflammatory pathways. For example, restricting calorie or protein intake in mice or introducing mutations in nutrient-sensing pathways can extend lifespans by as much as 50%. These ‘Methuselah mice’ are more likely than controls to die without apparent disease. In Rhesus monkeys, dietary restriction (DR) also increases lifespan and protects against obesity, diabetes, heart disease, cancer, brain aging and frailty, and in humans it causes physiologic, metabolic and molecular changes that protect against these pathologies. Moreover, recent findings indicate that meal timing is crucial, with both intermittent fasting and time-restricted feeding improving health and function in the absence of changes in overall intake. Lowered intake of particular nutrients is also key in mediating some of the effects of DR, with protein and specific amino acids and nutritional modulation of the microbiome playing prominent roles.

More studies are needed to understand the interactions between calorie intake, single nutrient modifications, exercise, and other lifestyle interventions in preventing or slowing the incremental build-up of molecular damage leading to metabolic dysfunction and tissue degeneration, eventually culminating in multiple organ pathologies.



Luigi Fontana is an internationally recognized physician scientist and one of the world’s leaders in the field of nutrition and healthy longevity in humans. His pioneering studies on the effects of dietary restriction in humans have opened a new area of nutrition-related research that holds tremendous promise for the prevention of age-related chronic diseases and for the understanding of the biology of human aging.  

Prof. Fontana is the Leonard P. Ullmann Chair of Translational Metabolic Health at the Charles Perkins Centre, where he directs the Healthy Longevity Research and Clinical Program. He is also a Professor of Medicine and Nutrition in the Faculty of Medicine and Health at the University of Sydney and a Clinical Academic in the Department of Endocrinology at the Royal Prince Alfred Hospital. Fontana is an Adjunct Professor of Medicine at Washington University School of Medicine in St. Louis, USA.

Prof. Fontana was a Full Professor of Medicine and Nutritional Sciences at Washington University in St. Louis (USA) and Brescia (Italy) Schools of Medicine, and co-director of the Longevity Research Program at Washington University.  He graduated with the highest honors from the Verona University Medical School (1994), where he completed his internship and residency in Internal Medicine (1999). He also received a PhD in Metabolism and Clinical Pharmacology from the University of Padua Medical School (2003).

Prof. Fontana has published over 120 manuscripts in prestigious journals including Science, Nature, Cell, New England Journal of Medicine, JAMA, BMJ, Cell Metabolism, Lancet Diabetes Endocrinology, Circulation, Journal American College of Cardiology, Diabetes, Aging Cell and PNAS. He has been invited to present his work at international conferences and top medical schools and research institutes around the world, including Harvard University, Cambridge University, Yale University, Universitè Paris “Pierre et Marie Curie”, Max Plank Institute of Aging, Baylor College of Medicine, Buck Institute for Research on Aging, Spanish National Cancer Research Centre, National University of Singapore among others. 

Prof. Fontana is the recipient of three prestigious awards: the 2009 American Federation Aging Research (AFAR) Breakthroughs in Gerontology Award, the 2011 Glenn Award for Research in Biological Mechanisms of Aging, and the 2016 Vincent Cristofalo Award of the American Federation Aging Research.  



 Host: Carolina Florian