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It doesn’t take much to find all sorts of claims online and elsewhere (books, podcasts, diets, advertising) promising wellness and longevity. So many products. So many medications.
What About the Science?
Recently, an article by Dr. F. Perry Wilson from Yale School of Medicine looked into longevity science. He highlighted two fundamental problems with the science.
The first one is that many of the investigations into longevity rely on observational data, hoping to find an indication that a given supplement, food, or exercise will positively correlate with a longer life span. Observational data relies on recall. Unfortunately, our ability to remember things accurately has been shown to be influenced by many potential distractions, rendering it an unreliable source of information.
Observations are often subjective. When we are putting something in our bodies, we never get a clear picture of how that something is affecting us. Bodies are complex, perceptions are complex, making it impossible to isolate how one substance or action is impacting them.
Secondly, creating randomized, controlled trials that are the gold standard in medical research has its own set of problems. They can be expensive to set up. Wilson mentions that organizations like the National Institutes of Health are not very interested in funding studies that focus on longevity. Their focus is mainly on disease diagnosis and treatment.
Disease investigations can often be concluded within five years or less. Clearly, studies looking into longevity would have to cover a much longer span of time. And, the longer a study goes, the greater is the chance that study subjects will stop being compliant with the intervention, develop health issues that could confound results, or have significant changes in lifestyle.
Randomized Controlled Study
So, what happens if/when there is a long-term, large, randomized, controlled study? This type of study is considered the gold standard of research.
Such was the case in a study Wilson found in the JAMA this past month (June, 2026).
A large randomized trial that started back in 2002 collected data on individuals with prediabetes. They were divided into three groups. One group was given an intensive lifestyle intervention, one group was given metformin (a well-known drug for treating prediabetes and diabetes), and one group got a placebo pill. The average age of participants was 51 at the beginning of the study. The study then went on for 21 years.
Once participants began to access Medicare, researchers were able to use those records to assess health conditions that arose as subjects got older. As noted by Dr. Wilson, there is good evidence that there is “an accelerating accumulation of chronic diseases” as we age. He went to observe that longevity really has to do with the ability to accumulate fewer chronic diseases, not be free of them. These diseases are known as multi-morbidities when there are two or more of them in an individual.
Results out of the gate were impressive. This would have been when the study population was at its youngest. Over three years, metformin reduced the risk of moving on to develop type 2 diabetes by 31% over the placebo. Even more impressive, however, was that lifestyle modification reduced that risk by 58%. This speaks volumes for the efficacy of a lifestyle intervention over this particular medication, and over this period of time.
If we scroll ahead to the end of the study, we find a different story. Most people developed multi-morbidities. Looking at raw data, the difference between outcomes in the lifestyle, metformin, and placebo groups were not significant. However, after adjusting for more specifics, the lifestyle group came ahead again. When the authors restricted outcomes to the most costly morbidities (for example, stroke, chronic kidney disease, chronic obstructive pulmonary disease), lifestyle reduced risk by 43%; metformin and placebo had no effect. Even when just looking at prevention of type 2 diabetes, lifestyle came out ahead over placebo or metformin at the end of the study.
What Questions Remain?
The most glaring question here is the extent of adherence to the metformin and lifestyle interventions over such a long period of time. Researchers reported that use of metformin declined over time, as did participation in the lifestyle intervention at initial intensity. They noted that physical activity was highest in the lifestyle intervention group for six years, and then it became similar to activity reported by the metformin group.
What can we make of all this?
- It’s worth noting that, even though lifestyle changes are often a tough sell and require more extensive follow-up than remembering to take a pill, adherence lasted for a significant time before backsliding occurred. Additionally, many people tend to exercise less as they get older, for various reasons.
- This study did end up showing that lifestyle change is an effective way to stave off disease, which may help a person live longer and healthier.
- It was an ambitious study. The groups were carefully randomized, only one medication was studied, and the study went far longer than most. Significance was found in outcomes, mostly for lifestyle changes. But can we say for certain that study subjects will live longer? No.
- This study, because of its length, used Medicare records to track disease, but it would have been relying on recall and subjective assessments from the subjects regarding adherence to the intervention.
This study highlights, again, many of the problems inherent when trying to study long-term effects of an intervention. Longevity of participants was still in question, with only inferences made based on development of chronic disease. Even so, it’s impressive that lifestyle intervention, which is much more complex to design and much more complex for an individual to participate in, appears to have won the day.
