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| Autores principales: | , , , , |
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| Formato: | Artículo científico |
| Lenguaje: | en |
| Publicado: |
Human genomics
2025
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| Acceso en línea: | https://pubmed.ncbi.nlm.nih.gov/40410862/ |
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| _version_ | 1868266201695649793 |
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| author | Fabian, Paul Blander, Gil Deehan, Renee Torkamani, Ali Nogal, Bartek |
| author_facet | Fabian, Paul Blander, Gil Deehan, Renee Torkamani, Ali Nogal, Bartek Fabian, Paul Blander, Gil Deehan, Renee Torkamani, Ali Nogal, Bartek |
| collection | PubMed - marine biology |
| contents | Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers. Fabian, Paul Blander, Gil Deehan, Renee Torkamani, Ali Nogal, Bartek Humans Fish Oils Epigenesis, Genetic Mendelian Randomization Analysis Biomarkers Aging Fishes Genome-Wide Association Study Animals Seafood Male Female Fatty Acids, Omega-3 Middle Aged Triglycerides Aged 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. 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. 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). 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 | Artículo científico |
| id | pubmed_40410862 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Human genomics |
| record_format | pubmed |
| spellingShingle | Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers. Fabian, Paul Blander, Gil Deehan, Renee Torkamani, Ali Nogal, Bartek Humans Fish Oils Epigenesis, Genetic Mendelian Randomization Analysis Biomarkers Aging Fishes Genome-Wide Association Study Animals Seafood Male Female Fatty Acids, Omega-3 Middle Aged Triglycerides Aged Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers. Fabian, Paul Blander, Gil Deehan, Renee Torkamani, Ali Nogal, Bartek Humans Fish Oils Epigenesis, Genetic Mendelian Randomization Analysis Biomarkers Aging Fishes Genome-Wide Association Study Animals Seafood Male Female Fatty Acids, Omega-3 Middle Aged Triglycerides Aged 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. 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. 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). 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. |
| title | Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers. |
| topic | Humans Fish Oils Epigenesis, Genetic Mendelian Randomization Analysis Biomarkers Aging Fishes Genome-Wide Association Study Animals Seafood Male Female Fatty Acids, Omega-3 Middle Aged Triglycerides Aged |
| url | https://pubmed.ncbi.nlm.nih.gov/40410862/ |