Mice live longer on high fat diet

12 September 2017

Interview with

Jon Ramsey, University of California, Davis

For years we’ve been told - for the benefit of good health - to keep fat intake to a minimum. That makes the discovery, announced last week - that a diet where most of the calories come from fat makes mice live 13% longer and stay active and healthy further into old age - very surprising. Eating a high fat diet induces a state that’s called  ketosis and somehow this alters metabolism into a life-prolonging state. So what should be on the menu? Chris Smith spoke to Jon Ramsey to find out more...

Jon - This is a diet that’s become increasingly popular. Breakfast, for example might be to have a couple of eggs, avocado on the side, milk with some heavy cream. Then for lunch it might be something like having a leafy green salad with some salmon on top and an oily dressing and perhaps some butter. There are a range of options that are out there that people are following to try to make this diet as palatable as possible.

Chris - What’s bizarre is that what you’ve just described sounds like, based on all of the literature that’s been put out, a heart attack waiting to happen - for want of a better phrase. Yet you’re saying, you feed this to mice with the intention of seeing if they’ll live longer?

Jon - That’s correct. There’s been a number of potential concerns with these types of diets as people have been using them and one of our goals was just to say we haven’t seen a lot of long term studies. We wanted to do a study that, frankly, we wouldn’t be able to do in humans and that was just to say if we could carefully control a diet started at middle age and continue it for the rest of life, what impact would it have on health and lifespan?

Chris - What did you actually do with these mice? Just tell me the structure of the experiment and what measurements you made and then what you found?

Jon - There were basically two groups of mice. One group was involved in lifespan portion and for those mice we didn’t do anything except feed the diet, weigh the animals weekly, and then just measure age at death and then, at death, we determined cause of death. In a separate group of animals at middle age, and then again at later life, we did a range of tests to look at basic functions, so measures of memory, muscle strength, muscle coordination, muscle endurance and formation.

Chris - And to be clear, you began these dietary interventions when these mice were already in what would the mouse equivalent of middle age, so that would be like a human 50 year old?

Jon - That’s correct. We purposely picked that age because that’s the time when many humans are thinking about changing their diet.

Chris - What happened to these mice then?

Jon - What we saw in the lifespan side is that there was an increase in lifespan and, in particular, in medium lifespan there was an increase of about 13%. In humans, a 13% increase in median lifespan would be about 7 to 10 years. As far as physiological function, I think that’s where we really saw the interesting and exciting changes. Memory was improved compared to control mice, measures of muscle strength and muscle endurance, and coordination were increased in the ketogenic diet compared to the control animals. The really striking thing was that in those older animals they were able to maintain function very similar to what we saw in middle aged animals.

Chris - So, in other words, you’ve got mice remaining at high quality function into older age, and they’re also going further into older age than animals that eat what we would regard as a normal diet?

Jon - That’s correct.

Chris - Do you know how or why? It’s extraordinary to see such a big difference in longevity.

Jon - Well, that’s the million dollar question right now - we don’t know why. We have some possible ideas and we looked at couple of possible mechanisms. But people have been studying ketogenic diets for nearly a hundred years and there’s still intense debate as to the possible mechanisms through which this diet works. I think this is an area where there just needs to be additional work in the future to try to better understand the cellular mechanisms that are driving some of these changes we see with the ketogenic diet.

Chris - Jon, you have to tell me before you go, do you eat this sort of diet off the back of what you discovered - what did you have for breakfast?

Jon - I have experimented a little bit with this diet, but I would have to say no, I have not been following it. Part of the reason that I haven’t yet is I haven’t yet answered the question that I really wanted to address, and that was to try to look at shifts in metabolism that occur with calorie restriction. With calorie restriction, the animals aren’t in continuous ketosis and so I think that’s the next  step. I really would like to look at that and if I notice changes with that approach I think it would be possible to design a diet that would be much easier to follow.

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