Understanding Fatty Acids
Before exploring our main topic, let’s begin with some fundamental knowledge about fatty acids.
Fatty acids can be classified into four basic groups based on their carbon chain length:
- short-chain fatty acids (SCFAs), containing one to six carbon atoms (C1–6), form through carbohydrate fermentation by gut microbiota in mammalian digestive tracts
- medium-chain fatty acids (MCFAs), containing seven to 12 carbon atoms (C7–12)
- long-chain fatty acids (LCFAs), containing 14 to 18 carbon atoms (C14–18), which make up most dietary fatty acids
- very long-chain fatty acids (VLCFAs), containing more than 20 carbon atoms (C > 20)
Fatty acids can also be categorised into saturated and unsaturated subgroups. The unsaturated category includes monounsaturated fatty acids (MUFAs), such as omega-9 fatty acids, and polyunsaturated fatty acids (PUFAs) (Cholewski et al., 2018).
Within the PUFA category, we find omega-6 and omega-3 fatty acids, which are the focus of this article.
Omega-3 fatty acids, a type of PUFA, are considered essential because human cells cannot produce them independently (Champigny et al., 2018). While some researchers consider all PUFAs essential, particularly highlighting linoleic acid (LA, an omega-6) and alpha-linolenic acid (ALA, an omega-3) as “parent essential fatty acids,” others focus on arachidonic (AA, an omega-6) and linoleic acids due to their role in growth and skin health. Mammalian research identifies 23 essential acids, while aquatic research focuses on just two omega-3s: EPA and DHA (Cholewski et al., 2018).
For our discussion of longevity, we’ll focus on three key omega-3 fatty acids: linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) (Xie et al., 2021).
While the body cannot create omega-3 fatty acids from scratch, it can convert ALA (an 18-carbon fatty acid) into EPA (20 carbons) and subsequently into DHA (22 carbons) through enzymatic processes – but more on this process shortly (Xie et al., 2021).
ALA primarily comes from plant sources, especially seeds, nuts, and certain vegetable oils. Rich sources include flaxseed, chia seeds, walnuts and canola.
While safflower, sunflower, corn, and soybean oils contain high amounts of linoleic acid (LA, an omega-6), flaxseed oil is particularly rich in ALA (49.2 g/100 g).
For EPA and DHA, the best sources are fish oils, particularly from salmon, sardines, and herring (Shahidi & Ambigaipalan 2018).
An important nuance often overlooked is that nutritional choices aren’t black and white. While salmon is rich in EPA and DHA and eggs contain more saturated fats, this doesn’t mean we should exclusively eat salmon and completely avoid eggs. Eggs also contain omega-3 fatty acids, just in smaller quantities than salmon. It’s worth remembering that we consume whole foods, not isolated nutrients.
Why Omega-3 Fatty Acid Supplementation Is Important
Two key challenges affect omega-3 levels in the body: omega-6 fatty acids compete with omega-3s for the same enzymes, and Western diets contain an excess of omega-6s.
The human body’s ability to convert ALA into EPA and DHA is remarkably inefficient. According to Shahidi & Ambigaipalan, only 0.2% of ALA converts to EPA, and a mere 0.05% converts to DHA.
Most people don’t get enough EPA and DHA through diet alone. This deficiency, combined with high omega-6 consumption, creates an unfavourable ratio of omega-6 to omega-3 fatty acids.
Understanding Ageing
Ageing is a complex biological process characterized by multiple interconnected mechanisms that contribute to the gradual decline of cellular and organismal function over time. Scientists have developed various frameworks to understand these mechanisms, with one prominent model being the Seven Pillars of Aging. This comprehensive framework breaks down the ageing process into distinct but interrelated biological components: inflammation (chronic low-grade inflammation that increases with age), metabolism (changes in how cells process energy and nutrients), epigenetics (alterations in gene expression patterns without DNA sequence changes), adaptation to stress (declining ability to respond to environmental challenges), stem cells and regeneration (reduced capacity for tissue repair and maintenance), macromolecular damage (accumulation of damaged proteins, lipids, and DNA), and proteostasis (declining ability to maintain proper protein folding and function) (Doyle et al., 2018).
Research on Omega-3 and Aging Mechanisms
Let’s explore in detail how omega-3 fatty acids interact with and influence the fundamental pillars of ageing, according to recent scientific research:
- Inflammation
Omega-3 fatty acids, particularly EPA and DHA, act as activators for anti-inflammatory transcription factors. They compete with AA (arachidonic acid, sometimes encoded as ARA, omega-6 acid) to bind to substrates in enzymatic pathways, inhibiting the conversion of AA into pro-inflammatory molecules (Qiu et al., 2024). - Metabolism
Omega-3 fatty acids play a crucial role in metabolic regulation by influencing gut microbiota composition and function. They enhance fatty acid metabolism and improve nutrient absorption through multiple pathways in the digestive system (Qiu et al., 2024). So we could say that the impact of omega-3 and omega-6 fatty acids on ageing is partially mediated by the gut microbiome, including Actinobacteria, Bifidobacteria, and Streptococcus (Xie et al., 2021). - Epigenetics
Through complex mechanisms, omega-3 fatty acids influence DNA methylation patterns and modulate the expression of genes associated with longevity. This epigenetic regulation can have long-lasting effects on cellular function (Xie et al., 2021). - Adaptation to stress
These essential fatty acids enhance cellular resilience by activating the Nrf2 pathway and upregulating protective enzymes like HO-1. This provides a crucial defence against oxidative damage and environmental stressors (Qiu et al., 2024). - Stem cells and regeneration
Research has demonstrated that omega-3 fatty acids support nervous system development and maintenance, potentially influencing stem cell function and tissue regeneration capabilities (Xie et al., 2021). - Macromolecular damage
While studies show mixed results, a mini meta-analysis suggests that omega-3 fatty acids may have a role in telomere maintenance (Ali et al., 2022). The decrease in the omega-6:omega-3 ratio has been associated with longer telomere length, potentially due to reduced inflammatory processes and oxidative stress (da Silva et al., 2022).
While these studies suggest that omega-3 fatty acids may contribute to cellular longevity by helping maintain telomere length, this relationship remains under investigation and shouldn’t be considered definitively proven (Ali et al., 2022). - Proteostasis
Omega-3 fatty acids significantly impact cellular membrane properties and signalling pathways, contributing to proper protein folding and cellular homeostasis maintenance (Qiu et al., 2024).
Recommended Intake
To achieve beneficial effects, research indicates that adults should consume 250-500mg of combined EPA and DHA daily (Wu et al., 2024). This dosage supports healthy ageing across multiple physiological systems. Note that the FDA recommends limiting combined EPA and DHA intake from dietary supplements to 5g per day (Izadi et al., 2024).
Take-Home Message
Research demonstrates that omega-3 fatty acids may slow ageing through multiple pathways—improving brain function and structure, reducing inflammation, modulating immune responses, and enhancing mitochondrial function (Wu et al., 2024).
The EPA/AA ratio is particularly significant, as higher ratios correlate with lower all-cause mortality (Qiu et al., 2024).
For optimal results, focus on two key ratios:
- Lower the omega-6 to omega-3 ratio in your diet.
- Increase the omega-3 to total fatty acids ratio in your blood (aim for an Omega-3 Index above 8%) (Alsmari et al., 2023).
Before beginning supplementation, consider getting a blood panel analysis to measure your fatty acid and omega-3/omega-6 ratios. This will make it easier to adjust your omega-3 supplementation dosage, leading to more effective intervention.
Select high-quality fish oil supplements to avoid heavy metal contamination.
References
Ali, S. R., Amer, S. A., Abd-El Hameed, M. A., Hamza, M. A., & Hassan, M. A. (2022). The association between omega-3 supplementation and telomere length and telomerase activity: A mini meta-analysis. Lipids in Health and Disease, 21(1), 1-10. doi:10.1186/s12944-022-01662-6
Alsmari, W., Algethami, M. R., Felemban, E. M., Aldahlawi, A. M., & Algethami, S. R. (2023). The Role of Omega-3 Fatty Acids in Human Health: A Review. Current Nutrition & Food Science, 19(4), 460-472. doi:10.2174/1573401318666220719121310
Champigny, C. M., McNamara, R. K., & Stark, K. D. (2018). Omega-3 fatty acid deficiency throughout the lifespan: An overview with emphasis on the brain. Nutrients, 10(8), 1046. doi:10.3390/nu10081046
Cholewski, M., Tomczykowa, M., & Tomczyk, M. (2018). A comprehensive review of chemistry, sources and bioavailability of omega-3 fatty acids. Nutrients, 10(11), 1662. doi:10.3390/nu10111662
da Silva, G. C., Lyra e Silva, N. M., Sabia, A. C., & de Miranda Netto, M. V. (2022). Dietary factors and telomere length: A systematic review. European Journal of Clinical Nutrition, 76(4), 1-11. doi:10.1038/s41430-021-00996-1
Doyle, K. E., Brown, J. L., & Rasheed, A. (2018). Identifying core pillars of aging: A review of biological mechanisms. Aging Cell, 17(4), e12814. doi:10.1111/acel.12814
Izadi, M., Khorshidi, M., Khodadadi, S., & Mohammadi, H. (2024). Omega-3 fatty acids and human health: An updated systematic review. Journal of Functional Foods, 81, 105575. doi:10.1016/j.jff.2023.105575
Qiu, X., Krogh, V., Ricceri, F., & Bosetti, C. (2024). Omega-3 fatty acids and healthy aging: A systematic review. Nutrients, 16(1), 156. doi:10.3390/nu16010156
Shahidi, F., & Ambigaipalan, P. (2018). Omega-3 polyunsaturated fatty acids and their health benefits. Annual Review of Food Science and Technology, 9, 345-381. doi:10.1146/annurev-food-111317-095850
Wu, J., Wilson, K. M., Stampfer, M. J., & Willett, W. C. (2024). Omega-3 fatty acids and mortality risk: A systematic review and meta-analysis. BMJ Nutrition, Prevention & Health, 7(1), e000614. doi:10.1136/bmjnph-2023-000614
Xie, D., Gong, M., Wei, W., & Jin, J. (2021). Understanding the role of omega-3 fatty acids in aging: A review of mechanisms related to inflammation and gut microbiota. Nutrients, 13(11), 4079. doi:10.3390/nu13114079
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