Background: The interplay between diet and healthspan is a topic of great interest in biomedical research. Toward this end, consumption of marine omega-3 fatty acids is of particular significance, as reports suggest that diets focused on seafood can prolong the disease-free portion of the human lifespan. Fish consumption has also been linked to reduced biological aging as measured by epigenetic clocks, but there is no conclusive evidence of a causal relationship. Moreover, fish oils reduce triglycerides, and may affect other lipid profiles, as well as systemic inflammation. To investigate further, we used two-sample Mendelian randomization to infer causality between fish intake and healthspan markers.
Methods: We perform bidirectional Mendelian randomization in the two-sample setting using publicly available GWAS summary statistics repositories. Usingoily fish consumption and fish oil supplementation as the primary exposures, we attempt to elucidate the causal landscape of these interventions on first- and second-generation epigenetic clocks as well as serum proxies of lipidemia and systemic inflammation.
Results: We report that oily fish consumption appears to causally modify PhenoAge (p < 0.0074), whereas it begins to approach causality with respect to GrimAge (p = 0.097). However, fish oil supplements do exhibit a causal relationship with GrimAge (p = 0.037). Both omega-3 exposures modify the epigenetic clocks in the expected negative, or age-decelerating, direction. We also confirm the causal relationship between fish oil consumption and triglyceride reduction (p = 0.004), though HDL and LDL were not significantly modified. Finally, we also detect suggestive causality between oily fish consumption and reduced hsCRP (p = 0.062).
Conclusions: Our analysis shows that consuming fish oil, whether through whole food or as a supplement, can have a rejuvenating impact as measured by PhenoAge and GrimAge acceleration. We have also confirmed the causal link between fish oil intake and lower triglyceride levels. These results, based on robust MR-based analyses, emphasize the effectiveness of dietary choices in influencing healthspan.
Exercise is effective toward delaying or preventing chronic disease, with a large body of evidence supporting its effectiveness. However, less is known about the specific healthspan-promoting effects of exercise on blood biomarkers in the disease-free population. In this work, we examine 23,237 generally healthy individuals who self-report varying weekly running volumes and compare them to 4,428 generally healthy sedentary individuals, as well as 82 professional endurance athletes. We estimate the significance of differences among blood biomarkers for groups of increasing running levels using analysis of variance (ANOVA), adjusting for age, gender, and BMI. We attempt and add insight to our observational dataset analysis via two-sample Mendelian randomization (2S-MR) using large independent datasets. We find that self-reported running volume associates with biomarker signatures of improved wellness, with some serum markers apparently being principally modified by BMI, whereas others show a dose-effect with respect to running volume. We further detect hints of sexually dimorphic serum responses in oxygen transport and hormonal traits, and we also observe a tendency toward pronounced modifications in magnesium status in professional endurance athletes. Thus, our results further characterize blood biomarkers of exercise and metabolic health, particularly regarding dose-effect relationships, and better inform personalized advice for training and performance.
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