Caloric Restriction Risks for Aging and Immune System Health

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• Caloric Restriction Beyond Obesity Prevention
• Human Studies Challenges
• Immune System Risks
• Risk-Reward Evaluation
• Case Study: Roy Walford
• Lack of Human Evidence
• Full Transcript

Caloric Restriction Beyond Obesity Prevention

Dr. Matt Kaeberlein, MD, PhD, addresses whether caloric restriction benefits stem merely from obesity prevention. He states this is very unlikely to be the case. Laboratory rodent studies show lifespan benefits extend beyond maintaining normal body weight. Dr. Kaeberlein believes caloric restriction probably has positive effects on biological aging in people.

Human Studies Challenges

Dr. Matt Kaeberlein, MD, PhD, explains the difficulty in studying caloric restriction in humans. Humans age slowly and live long lives, making long-term controlled studies nearly impossible. This complexity creates significant challenges for definitive conclusions. Genetic heterogeneity and complex environments add further layers of uncertainty to human caloric restriction research.

Immune System Risks

Dr. Matt Kaeberlein, MD, PhD, highlights a critical concern with chronic caloric restriction. He speculates that nutritional restriction could increase infection risk. A compromised immune system might fail to fight off pathogens like influenza or COVID-19 effectively. This potential side effect represents a serious consideration for anyone practicing severe dietary restriction.

Risk-Reward Evaluation

Dr. Matt Kaeberlein, MD, PhD, emphasizes the importance of risk-reward analysis for longevity strategies. He cautions that diet gurus often ignore potential negative consequences of their recommended diets. Nutritional strategies can have significant side effects that are frequently overlooked. Dr. Kaeberlein stresses that cultural attitudes often fail to recognize diets as having potential harms.

Case Study: Roy Walford

Dr. Anton Titov, MD, references famous caloric restriction researcher Roy Walford during their discussion. Dr. Walford authored "The 120-Year Diet" but died at age 79. Dr. Matt Kaeberlein, MD, PhD, notes that Walford suffered from ALS. He clarifies this connection remains speculative regarding caloric restriction's influence.

Lack of Human Evidence

Dr. Matt Kaeberlein, MD, PhD, discusses the absence of evidence supporting extreme longevity through caloric restriction. No documented cases exist of long-term practitioners reaching even 110 years. While this doesn't disprove potential benefits, it shows limited supporting data. Anecdotal evidence from small numbers of individuals provides insufficient proof for lifespan extension claims.

Full Transcript

Dr. Anton Titov, MD: So, in your recent science feature article about diets and aging, there are several very interesting finer points that you make with your co-authors. One of them is: is it possible that all caloric restriction does is help us perhaps avoid obesity? So there is perhaps no magic in it? Or what can help? What can you comment on that?

Dr. Matt Kaeberlein, MD: I think that's a reasonable question. My personal feeling is that it's very unlikely to be the case. Obesity, whether in laboratory rodents or in people, is associated with and almost certainly causal for a variety of negative health outcomes during aging.

Maintaining normal body weight certainly in mice gives further benefits for lifespan from caloric restriction, as opposed to what we would consider a normal or healthy body weight with moderate adiposity. So my personal feeling is it's very unlikely that the effects of caloric restriction are simply due to preventing obesity.

In humans, it's a harder question to answer. In part, that's because humans age so slowly and live a long time. Really, nobody can do long-term controlled studies of caloric restriction. So in that context, it's harder to know whether moderate or even severe caloric restriction long-term in people would positively impact the biology of aging.

It's a guess. As long as we recognize that it's a guess, then I'm comfortable saying my guess is that caloric restriction, beyond just preventing obesity, probably has positive effects in people on biological aging.

My concerns are that because people live in a very complicated environment and are genetically heterogeneous, there is a risk associated with severe or even moderate long-term caloric restriction in people that is not appreciated based on mouse and rat studies in the laboratory.

When you're thinking about strategies to maximize healthy longevity, you always need to think about the risk-reward ratio. We know that there are some pretty potentially big rewards from positively modifying the biological aging process and enhancing lifespan.

But there are also risks associated with any strategy that we take. In the context of caloric restriction, one obvious example would be that if you're chronically calorically restricted, there's a pretty reasonable chance that you're going to be at higher risk of infection, or at least failure to fight off an infection once infected.

That's speculation, but I think it's a reasonable speculation. If that's the case, it doesn't do you any good if you're aging more slowly but get infected with influenza or COVID-19 and die because you're in a nutritionally restricted state that isn't able to fight off the infection as effectively.

I just say that to make the point that it's hard to answer the question that you asked definitively. Even if caloric restriction has significant benefits in the context of aging, I'm not convinced that the benefits will offset the risk that goes along with long-term caloric restriction in people.

That was another point that we tried to make. Some of these diet gurus that get on the internet and try to sell their favorite diet don't really evaluate the potential negative consequences and side effects associated with some of these diets.

Culturally, we're not trained to think of diets or nutritional strategies as having side effects, but they do. I think it's important to appreciate that.

Dr. Anton Titov, MD: I think you also mentioned in the review that the famous caloric restriction researcher, Roy Walford, tried to popularize and did write a very famous book on caloric restriction. He died at 79, so quite short of the 120 years that he proposed. Do you know what is the cause of death?

Dr. Matt Kaeberlein, MD: It's my understanding that Dr. Walford suffered from a form of ALS. I think it's total speculation whether or not that was at all impacted by his quite public adoption of caloric restriction; nobody knows.

This is a challenge with interpreting anecdotal data from people who have been practicing caloric restriction because it's always very small numbers of individuals. But I think the point is valid that he wrote a book called "The 120-Year Diet," making the case that caloric restriction would likely allow most people to reach that threshold of 120 years, which is still viewed as the longest natural lifespan in people.

Certainly, in his case, he didn't make it. As far as I know, there aren't any examples of people who practiced long-term caloric restriction who reached even 110 years. It doesn't disprove the idea that caloric restriction could allow some people to achieve extreme healthy old age, but I don't think there's a lot of data to support that at this point.