Human Aging
Calorie Restriction and the Future of Aging
Luigi Fontana, M.D., Ph.D.
Professor of Geriatrics and Nutritional Science, Washington University in St. Louis School of Medicine Professor of Medicine and Nutritional Sciences, University of Brescia, Italy
Luigi Fontana, M.D., Ph.D., FRACP, is an internationally known human systems biologist and a world leader in the study of nutrition and the biology of human aging. One of the original founders of the Longer Life Foundation’s Longevity Research Program, he is currently Professor of Medicine and Nutrition, Leonard P. Ullman Chair in Translational Metabolic Health, and Director of the Healthy Longevity Research and Clinical Program at the University of Sydney. His research interests incorporate the processes of aging and age-related diseases, including cardiovascular function, glucose metabolism, inflammation, neuroendocrine and immune function, and microbiome and cancer biology.
In this 2018 Q&A, Dr. Fontana discussed several aspects of his constantly evolving research on calorie restriction – a regimen that reduces caloric intake without incurring malnutrition – and the potential for related discoveries to impact the future of how humans age.
Q:
What are the main factors you see as predictive of longevity and wellness?
A:
Over the years several factors have emerged – smoking, lack of exercise, and the most interesting one – sleep. Research published in the journal Nature in 2013 discussed the two-way relationship ofsleep and Alzheimer’s disease, which highlighted the fact that sleep disruption increases the deposition of beta amyloids and tau protein in the brain. There are a number of interventions that could be implemented that have been found over the past few years. I believe, though, that the only thing that can consistently and drastically increase life span is CR without malnutrition.
I believe, though, that the only thing that can consistently and drastically increase life span is CR without malnutrition.
Q:
How did you first get interested in researching calorie restriction?
A:
When I was in medical school, one of my professors talked about CR. I was interested in researching how to prevent disease, and CR clearly was a path to that end.
Q:
How and why does CR result in increased lifespans?
A:
CR results in increased lifespans by lowering the levels of several growth factors and hormones that drive cellular proliferation, which ultimately reduces the risk of damage to the body. Forexample, if insulin, testosterone, and inflammatory drivers are reduced, the organism benefits through increased genomic stability, and cells are made younger and less dysfunctional. Cellular senescence is also decreased.
Q:
Life expectancy and maximum life span are different. What do you think is the maximum human lifespan?
A:
Everyone has a genetic predisposition for disease/aging, but if a person does everything right, they might be able tolive longer than what their genes might determine. Right now, the maximum confirmed life span is 122 – the age atwhich Jeanne Calment, the oldest known and verified person, passed away. That being said, she was not doing CR or exercising. If someone with her genes did, I think they might live to 150.
Q:
How might an average person benefit from CR?
A:
Around 10-15 years ago, there were two main accepted dogmas about CR: one, the more CR the better; and two, macronutrients are not important. These are no longer the case. The picture today is more complex. It is clear that there is a specific degree and mode of CR that is right for every person. For example, with mice, when (that is, the time of day) they ate their calories made adifference in how CR affected their bodies. It will be interesting to see what happens when we move from mice to humans.
We don’t yet have a clear understanding of which CR interventions work on which pathways. My research has always focused on understanding which pathways are important, and how differentinterventions impact these pathways. Each CR option affects different pathways. Once we know what is affected by what, we can prescribe something depending on the specific factors.
Q:
Do you think a personalized CR-based approach might be possible as a way to treat conditions such as obesity or diabetes?
A:
Some research I did recently with Bettina Mittendorfer, Ph.D. (also an LLF investigator) found that people can lose weight and body fat without any metabolic benefits. Our study focused on the metabolic effect of high protein CR on insulin sensitivity for women.Participants all lost 10% of their body weight and lost fat as well, but surprisingly experienced no increase in their insulin sensitivity. However, other types of diets did improve their insulin sensitivity. Losing weight, we found, will not provide a metabolic benefit unless the diet is done right.
Q:
What do you think is the potential of CR in the future?
A:
Currently, people have high accumulations of molecular damage in their bodies. I believe CR has huge potential – not just to slow cellular aging and damage, but also to help diabetes, obesity, cardiovascular disease and cancers. CRprovides a framework for us to investigate the biology of aging from a range of novel perspectives.
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