Lipid Composition and Fatty Acid Role in Longevity and Aging

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• Fatty Acids and Lifespan Correlation
• Challenging Oxidative Damage Theories
• Omega-3 and Omega-6 Longevity Debate
• Lipidomics Research in Aging Dogs
• Lipidome vs. Metabolome in Aging
• Future Lipid Research Directions
• Full Transcript

Fatty Acids and Lifespan Correlation

Dr. Steven Austad, MD, reveals a spectacular correlation between fatty acid composition and animal lifespan. The nature of saturated and unsaturated fats in cellular membranes shows a strong relationship with longevity. This correlation is almost as significant as the well-established link between body size and lifespan. Dr. Austad's research indicates that longer-lived mammals tend to have different polyunsaturated fatty acid profiles. These findings provide crucial insights into the biological mechanisms of aging.

Challenging Oxidative Damage Theories

Dr. Steven Austad, MD, discusses how new research challenges traditional free radical theories of aging. The assumption was that long-lived animals would have fewer lipids with double bonds to avoid free radical attack. However, Dr. Steven Austad, MD, explains that naked mole rats present a fascinating exception to this rule. These long-lived rodents maintain very high levels of oxidative damage in their tissues yet achieve exceptional longevity. This discovery suggests that some species have evolved mechanisms to live with high oxidative stress, opening new research directions in aging biology.

Omega-3 and Omega-6 Longevity Debate

The interview with Dr. Anton Titov, MD, explores the popular supplementation of omega-3 fatty acids versus research findings on omega-6. Dr. Steven Austad, MD, notes that longer-lived animals show correlations with higher omega-6 polyunsaturated fatty acid levels. This presents a paradox given the widespread promotion of omega-3 supplements for health benefits. Dr. Steven Austad, MD, emphasizes that these comparative patterns are excellent for generating hypotheses but require species-specific experimentation for validation. The relationship between different fatty acid types and longevity remains an open and complex question in aging research.

Lipidomics Research in Aging Dogs

Dr. Steven Austad, MD, details his extensive lipidomics research using dogs as a model for human aging. His team analyzed the complete lipid profiles in blood from young and old dogs across different sizes. They discovered a substantial lipid signature distinguishing big, short-lived dogs from small, long-lived dogs. Sphingomyelin emerged as a particularly significant lipid associated with aging differences. Dr. Steven Austad, MD, explains that this research helps understand whether these differences relate to cellular membrane composition or cell signaling functions. The dog model provides valuable insights into how lipid metabolism influences lifespan and healthspan.

Lipidome vs. Metabolome in Aging

Dr. Steven Austad, MD, presents compelling data showing the lipidome's significant association with aging processes. His research found that 25% of the circulating lipidome correlates with weight and 17% with age. This suggests lipid profiles may be more strongly associated with longevity than the broader metabolome. Dr. Steven Austad, MD, emphasizes the importance of looking beyond traditional cholesterol and triglyceride measurements. He advocates for comprehensive lipidome analysis to better understand aging mechanisms. This approach represents a paradigm shift from focusing primarily on protein biology to embracing lipid diversity in aging research.

Future Lipid Research Directions

Dr. Steven Austad, MD, outlines the exciting future of lipid research in understanding human aging and health. He notes that science has focused predominantly on proteins while neglecting the hundreds of different lipid forms in the human body. Dr. Austad believes lipid biology may ultimately teach us more about aging than proteome biology. His research underscores the importance of dietary lipids and their modification potential for health optimization. Dr. Anton Titov, MD, facilitates this discussion about translating comparative biology findings to human health applications. The emerging field of lipidomics promises new insights into cognitive aging, dementia, and overall longevity.

Full Transcript

Dr. Anton Titov, MD: 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. Longer life mammals have more omega-6, or N-6 PUFAs, polyunsaturated fatty acids, whereas, for example, naked mole rats have low N-3 PUFAs. How does that translate to other species? What could be the mechanism? Why might such differences in particular fatty acid types correlate with a different lifespan?

Dr. Steven Austad, MD: That's a very interesting question. 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. 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. We don't understand that, but that might also teach us something about aging. That's very interesting.

Dr. Anton Titov, MD: Because supplementation with omega-3 fatty acids is very popular—omega-3 oil is everywhere—but it seems that as far as longevity is concerned, there is a correlation with more omega-6 polyunsaturated fatty acids and lifespan. Is there a correlation, or is it just semantics?

Dr. Steven Austad, MD: Yeah, I think that's the open question. Like many cases in comparative biology, I believe these large patterns are good at suggesting hypotheses, but they're not very good at answering those hypotheses. To answer those hypotheses, one has to tinker with the individual species.

Dr. Anton Titov, MD: 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?

Dr. Steven Austad, MD: Yes. So what we've done is this: we have done metabolomics and lipidomics, 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. We find that there's quite a substantial lipid signature, 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, but still we don't understand it. Is this something about the composition of the cellular membranes, or is it 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 may be more associated with longevity than the entire metabolome.

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?

Dr. Steven Austad, MD: 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.