#503 Scientists Analyzed 400 Drugs — Only 14 Were Linked to Longer Life - Dr. Kevin Perez

Kevin Perez (0:00)

People, diabetic people that were taking metformin, they appeared on average to live longer than even non-diabetic people. Why focus only on metformin? So we can do this really more systematically, looking at many drugs, all the drugs, all the medication that people are taking, and then looking at their overall survival. Instead of asking, okay, are there drugs that are associated with people living longer? You could ask, are there any drugs associated with a lower biological age, right?

Siim Land (0:33)

Kevin, welcome to the show.

Kevin Perez (0:35)

Hi, Siim. Thank you.

Siim Land (0:38)

Yeah, I'm happy to have you on the podcast, and I've read a few of your papers about anti-aging and longevity, which are very interesting, and I stumbled upon them quite frequently, so I decided to invite you to the podcast and discuss them in greater detail.

The first paper or one of the recent papers that I was reading, that you helped to write with your colleagues, was about these different pharmaceuticals and medicines that appear to be associated with a lower risk of mortality in the UK that you researched. So maybe we can start off with that particular paper about, what are some of these different medicines and the pharmaceuticals that could have some longevity benefits?

Kevin Perez (1:33)

Yeah, sure. I mean, maybe I can start with providing some background for the study. So I think this whole idea started from the drug metformin, actually. So probably, you know, metformin is a diabetes drug, and it's a very important drug in the aging field. Many people are interested in this drug. So one of the interesting facts about metformin is that there was a long-term study a few years ago, already was in the UK actually, same as our paper, but different cohorts. And so they followed people taking metformin for long-term, you know, for 10 years, et cetera. And they looked at their overall mortality, or cause mortality.

And there was a surprising finding in this study is that people, diabetic people that were taking metformin, they appeared on average to live longer than even non-diabetic people, like healthy, relatively healthy, non-diabetic people not taking metformin. So that was very surprising finding because you would not expect this. I mean, you have people that have diabetes, diabetes is a serious disease, it shortens your life expectancy. And then you see this patient taking metformin, they actually seem to live even longer than...

Siim Land (3:15)

That would be a huge result.

Kevin Perez (3:18)

Exactly. It was very surprising.

Actually, this study was not confirmed by follow-up subsequent studies, but we can talk about that later. But anyway, it was really the basis, I think, of our study. And what we thought was, okay, that's very interesting, but why focus only on metformin? I mean, there were some reasons. Prior, people have been in the aging field, they were interested in insulin resistance, diabetes, et cetera, and the effect on aging. And there were data in model organisms about metformin. So there were many reasons to look at these drugs. But why only focus on one drug? Now we have these big biobanks, these big cohorts where we know exactly all the medications that people are taking. We have a very long follow up now, up to 20 years and more. And so we can do this really more systematically, looking at many drugs, all the drugs, all the medications that people are taking. And then looking at the overall survival to see if they would live longer, that's what would be expected compared to match controls. And yeah, so that's what we did in this study. So we took one of the largest biobank, it's called the UK Biobank. It was one of the first, I would say, cohort to have read this biobank approach, open access. So it's half a million subjects. Very long follow up was started in 2006

So yeah, we did this in this cohort. So we looked at all the drugs that people were taking. So it's more than 400 drugs. And we, one by one, we systematically looked, okay, are the people that are taking these drugs living longer than matched control? So when I say matched control, I mean, when you do the studies, you cannot compare just people taking the drug versus people not taking the drug. You have to adjust for confounding factors. So the main one, first, you adjust for gender and age. Then you can adjust for some diseases like cardiovascular disease, cancer, et cetera, and then some more lifestyle factors like smoking, BMI, or things like that.

So we did this. We looked at all 400 drugs. And what we found was that, so as expected, most of the drugs we looked at were associated with worse mortality. This is expected. This doesn't mean that the drugs are bad. Of course, they are here for a reason, and they are treating diseases. It's just that very often, the underlying diseases that these drugs are prescribed for, they can shorten mortality. And even after we account for the confounder, it's still there, and it's very difficult to account for that. So that was not surprising. That was expected. It's called confounding by indication, if you find the term, but...