It's very interesting. Your research also mentioned some differences in polyunsaturated fatty acids between the animals who live longer and animals with shorter lifespans. And longer life mammals have more omega six, or N-6 PUFAS, polyunsaturated fatty acids, whereas, for example, naked mole rats have a low n-3 PUFAS. How does that translate to other species? And what could be the mechanism? Why might such differences in particular fatty acid types correlate with a different lifespan?
Yeah, that's a very interesting question. Dr. Steven Austad, PhD. Dr. Anton Titov, MD. Because it does turn out that the nature of saturated fat and unsaturated fats correlates with lifespan almost as well as body size, it's quite spectacular. The assumption has always been that long-lived animals will have membranes with fewer lipids with double bonds, which are a target of free radical attack. That was when free radical biology was really at the center of understanding aging. But we've kind of moved on from that. So now I would say, it's become more of a mystery than it was previously. Dr. Steven Austad, PhD. Dr. Anton Titov, MD. One of the things that's interesting, and one of the things we've learned from the naked mole rats, for instance, is that they have very high levels of oxidative damage in their tissues, something that we used to think was incompatible with a long life. But they have a way to live with those high levels of oxidized lipids, and we don't understand that, but that might also teach us something about aging. That's very interesting.
Because supplementation with Omega three fatty acids is very popular. Omega-three oil is everywhere. But it seems that as far as longevity is concerned, there is a correlation with more omega six polyunsaturated fatty acids and lifespan. Is there a correlation? Dr. Steven Austad, PhD. Dr. Anton Titov, MD. Or is it just the semantics? Yeah, I think that's the open question. Right? Like many cases in comparative biology, I believe these large patterns are good at suggesting a hypotheses. But they're not very good at answering those hypotheses. To answer those hypotheses, one has to tinker with the individual species.
In your research, you also showed extensively that lipid metabolism has a role in aging, as well as inflammation. Could you comment on your research on the link between lipid metabolism and cognitive aging, including dementia, such as Alzheimer's disease? Yes. Dr. Steven Austad, PhD. Dr. Anton Titov, MD. So what we've done is this. We have done metabolomics and lipidomics. It is an analysis of all the lipids in the blood of young and old species, young and old individuals, larger and smaller individuals. The work that we've done most extensively has been in dogs. And we find that there's quite a substantial lipid signature that as we find different lipid compositions in the blood of big dogs, short-life dogs, and small dogs, long-life dogs. Sphingomyelin stood out as showing [a connection to aging]. Still, we don't understand it. Is this something about the composition of the cellular membranes, as it is something that has something to do with the cell signal qualities. We're just starting to understand the diversity of lipids in our bodies. I think we've focused so much on proteins; we understand so much more about proteins that we're right at the very beginning of understanding our lipid biology. Ultimately that might teach us more than we're going to learn from proteome biology. That's very important because, as you write in one of your reviews, 'we found a relatively large proportion of the circulating lipidome was associated with weight (25%) and age (17%). So the lipidome maybe more associated with longevity than the entire metabolome. Dr. Steven Austad, PhD. Dr. Anton Titov, MD. Does that underscore the importance of keeping an eye on human lipid profile, cholesterol, triglycerides, and how they change throughout age? Absolutely, and not just those lipids, but the entire lipidome. Because this is new, I don't think anybody has been looking at this. We've just assumed that we can tell the whole story from other metabolites. But I think this interesting signature means that we need to learn more about diversity. I mean, there are hundreds of different lipid forms in the human body, we need to understand more about what they do and what modifying them might be able to do. But certainly, it focuses on the lipids that we eat.