Promoting healthy longevity through diet and exercise: metabolic and molecular mechanisms
About the speaker
Leonard P Ullmann (Picasso) Chair in Translational Metabolic Health Scientific Director, Charles Perkins Centre Royal Prince Alfred Clinic Director, CPC RPA ‘Health for Life’ Clinical, Research and Educational Program Faculty of Medicine and Health, University of Sydney Clinical Academic, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney
Prof. 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 clinical studies on the effects of dietary restriction have opened a new area of nutrition-related research that holds tremendous promise for the prevention of age-related chronic diseases. His research has delivered a paradigm shift in the understanding of how dietary restriction and exercise training, by slowing the accumulation of metabolic and molecular damage, deeply influence human aging biology and the initiation, progression and prognosis of many clinical conditions, ranging from obesity to type 2 diabetes, cardiovascular disease, cancer and dementia.
Abstract
Every day I see people who are suffering, and who mistakenly believe that their chronic diseases are due to bad genes or an unlucky roll of the dice. It is sad because we now know that many chronic illnesses are preventable. Modern medicine makes it possible for patients to escape early death and live with these conditions for decades, but these years are characterized not by joy, freedom, action and independence, but by suffering, anxiety, debility and dependence on increasingly costly medical systems.1,2 According to WHO, at least 80% of cardiovascular diseases and diabetes, and 40% of cancers are preventable. Accumulating data show that these numbers are conservative because multiple studies have shown that the accumulation of molecular damage can be prevented or much delayed by dietary, genetic, and pharmacological manipulations that down-regulate key cellular nutrient-sensing and inflammatory pathways.3
In rodents and monkeys, for example, dietary restriction without malnutrition protects against obesity, diabetes, cancer, cardiovascular disease, brain aging, and frailty, and in humans, this induces biological adaptations that protect against those illnesses as well as liver and kidney diseases.3,4 Minimizing weight gain during adulthood through regular exercise and a healthy Mediterranean-like diet is also key, but specific modulation of other nutritional factors (e.g., specific amino acids, fatty acids, vitamins, and phytochemicals) directly and/or through gut microbiome metabolism have been shown to potentiate their beneficial effects.5,6 Avoidance of smoking and alcohol consumption, cognitive training, improving sleep quality, reducing mental stress, and the cultivation of social connectedness, altruism, and compassion are also crucial in preventing a range of harmful physiological and psychological alterations.7
In summary, transitioning from a primarily disease-centered medical system to a more balanced preventive and mechanism-based personalized treatment healthcare system is key to promote global health and wellbeing, and to reduce social disparities in health and achieve financially sustainable, universal health coverage for all, while protecting planetary health.8
Key references:
1. Fontana L, Fasano A, Chong YS, Vineis P, Willett WC. Transdisciplinary Research and Clinical Priorities for Better Health. Plos Medicine 2021;18(7):e1003699.
2. Fontana L. From chronic disease to chronic health: the evolving role of doctors in the 21st century. Eur Heart J. 2024 Apr 12:ehae173.
3. Fontana L, Partridge L, Longo VD. Extending Healthy Lifespan—From Yeast to Humans. Science 2010;328(5976):321-6
4. Fontana L, Partridge L. Promoting Health and Longevity through Diet: from Model Organisms to Humans. Cell 2015;161:106-118
5. Green CL, Lamming D, Fontana L. Molecular mechanisms of dietary restriction promoting health and longevity. Nature Reviews Molecular Cell Biology 2022;23(1):56-73.
6. Fontana L. Interventions to promote cardiometabolic health and slow cardiovascular ageing. Nature Reviews Cardiology 2018;15(9):566-577.
7. Cagigas ML, Twigg SM, Fontana L. Ten tips for promoting cardiometabolic health and slowing cardiovascular aging. Eur Heart J. 2024;45(13):1094-1097.
8. Fontana L. The Path to Longevity. Hardie Grant Books, 2020.
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