Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers
Abstract 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 hu...
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2025-05-01
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| Online Access: | https://doi.org/10.1186/s40246-025-00756-3 |
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| author | Paul Fabian Gil Blander Renee Deehan Ali Torkamani Bartek Nogal |
| author_facet | Paul Fabian Gil Blander Renee Deehan Ali Torkamani Bartek Nogal |
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| description | Abstract 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 investigate potential causality between fish intake and healthspan markers. Methods Bidirectional Mendelian randomization was performed in the two-sample setting with publicly available GWAS summary statistics. GWAS data from the UK Biobank for oily fish consumption (n = 460,443) and fish oil supplementation (n = 461,384) were used as the primary exposures. First-generation epigenetic clocks Hannum age and intrinsic epigenetic age acceleration (IEAA), as well as second-generation clocks GrimAge and PhenoAge were collected from an independent dataset of individuals of European ancestry (n = [34,449–34,667]). Finally, data from the Integrative Epidemiology Unit database was used for serum proxies of lipidemia and systemic inflammation (n = [61,308–78,700]). Additional sensitivity analyses, such as reverse causation testing and the Cochran’s Q test were performed for exposure-outcome pairs where the inverse variance weighted (IVW) method was significant (p-value < 0.05), and where the MR Egger method indicated an effect in the same direction as the IVW result. Results We report that oily fish consumption appears to decrease PhenoAge acceleration (p < 0.0086), whereas fish oil supplementation appears to decrease GrimAge (p $$=$$ = 0.037). Both omega-3 exposures modify the epigenetic clocks in the expected negative, or age-decelerating, direction. For the serum biomarkers, we find evidence that fish oil consumption leads to a reduction in triglycerides (p $$=$$ = 0.004), although HDL and LDL were not significantly modified. Finally, we also detected a suggestive inverse relationship between oily fish consumption and hsCRP (p $$=$$ = 0.064). 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 provided evidence further linking fish oil intake and lower triglyceride levels. These results, based on robust MR-based analyses, emphasize the effectiveness of dietary choices in modifying emerging measures of healthspan. |
| format | Article |
| id | doaj-art-fdfab8c0b7de42acbc77d5bc22c52e34 |
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| spelling | doaj-art-fdfab8c0b7de42acbc77d5bc22c52e342025-08-20T01:53:14ZengBMCHuman Genomics1479-73642025-05-0119111410.1186/s40246-025-00756-3Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markersPaul Fabian0Gil Blander1Renee Deehan2Ali Torkamani3Bartek Nogal4InsideTrackerInsideTrackerInsideTrackerThe Scripps Translational Science Institute, The Scripps Research InstituteInsideTrackerAbstract 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 investigate potential causality between fish intake and healthspan markers. Methods Bidirectional Mendelian randomization was performed in the two-sample setting with publicly available GWAS summary statistics. GWAS data from the UK Biobank for oily fish consumption (n = 460,443) and fish oil supplementation (n = 461,384) were used as the primary exposures. First-generation epigenetic clocks Hannum age and intrinsic epigenetic age acceleration (IEAA), as well as second-generation clocks GrimAge and PhenoAge were collected from an independent dataset of individuals of European ancestry (n = [34,449–34,667]). Finally, data from the Integrative Epidemiology Unit database was used for serum proxies of lipidemia and systemic inflammation (n = [61,308–78,700]). Additional sensitivity analyses, such as reverse causation testing and the Cochran’s Q test were performed for exposure-outcome pairs where the inverse variance weighted (IVW) method was significant (p-value < 0.05), and where the MR Egger method indicated an effect in the same direction as the IVW result. Results We report that oily fish consumption appears to decrease PhenoAge acceleration (p < 0.0086), whereas fish oil supplementation appears to decrease GrimAge (p $$=$$ = 0.037). Both omega-3 exposures modify the epigenetic clocks in the expected negative, or age-decelerating, direction. For the serum biomarkers, we find evidence that fish oil consumption leads to a reduction in triglycerides (p $$=$$ = 0.004), although HDL and LDL were not significantly modified. Finally, we also detected a suggestive inverse relationship between oily fish consumption and hsCRP (p $$=$$ = 0.064). 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 provided evidence further linking fish oil intake and lower triglyceride levels. These results, based on robust MR-based analyses, emphasize the effectiveness of dietary choices in modifying emerging measures of healthspan.https://doi.org/10.1186/s40246-025-00756-3Oily fish intakeTwo sample Mendelian randomization2SMREpigenetic agingBiological agingSerum biomarkers |
| spellingShingle | Paul Fabian Gil Blander Renee Deehan Ali Torkamani Bartek Nogal Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers Human Genomics Oily fish intake Two sample Mendelian randomization 2SMR Epigenetic aging Biological aging Serum biomarkers |
| title | Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers |
| title_full | Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers |
| title_fullStr | Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers |
| title_full_unstemmed | Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers |
| title_short | Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers |
| title_sort | causal impact of genetically determined fish and fish oil intake on epigenetic age acceleration and related serum markers |
| topic | Oily fish intake Two sample Mendelian randomization 2SMR Epigenetic aging Biological aging Serum biomarkers |
| url | https://doi.org/10.1186/s40246-025-00756-3 |
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