So let's start with two hot words. Aging and diet, diet and aging. You know, what is the promise? What are the pitfalls? And what are the reality of aging and diet connections? Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD.
Sure. So I would say I think what we've learned from the preclinical studies in laboratory animals, particularly rodents, like mice and rats, is that diet can have a profound effect on the biological aging process on lifespan on healthspan as animals are getting older. The classic example of that is caloric restriction, which has been known since the 1930s to significantly increase lifespan in rodents. Then a whole series of work throughout the 20th century, I think, firmly established that caloric restriction not only increases lifespan but broadly delays declines in function that go along with the aging process. Or recently, you know, there has been a lot of interest in alternative nutritional strategies like a ketogenic diet or protein restriction or time-restricted feeding intermittent fasting, you know, trying to understand to what extent can these alternative nutritional interventions mimic some of the effects of caloric restriction in laboratory animals? Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. And I would say, you know, it's, it's, it's kind of a mixed bag at this point. None of the sorts of alternatives to caloric restriction have magnitudes of effects comparable to caloric restriction. However, there's certainly evidence that you can get some beneficial effects on healthy aging from some of these alternative dietary strategies. So it's an ongoing area of research. We've learned a lot. I think about the mechanisms that underlie caloric restriction and some of these other dietary interventions and laboratory animals. I'd say it's still a long way from being able to evaluate to what extent would caloric restriction or some of these alternative nutritional strategies impact the aging process in humans? Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. Certainly, there is correlative epidemiological evidence that populations who eat less have greater life expectancies. The Okinawans in Japan are a sort of classic example of that. The extent to which that's mediated through effects on biological aging, I think, is still unclear. And it's an area of active study. So I would say, you know, it's clear that nutrition impacts the biology of aging. We understand those mechanisms to some extent, but I'd say we're still a ways away from really being able to make strong recommendations to people about the specific dietary strategies that they should be taking to maximize their healthy longevity. Now, having said that, I think you know, generalizations certainly are reasonable. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. You know, not being overweight or obese clearly, is associated with better health outcomes during aging. But this specific strategy by which you achieve that, whether that's protein restriction or ketogenic diet or intermittent fasting and whether or not one of those is better than the others, I think is still a really open question.