| Title: | The role of phenylalanine and tyrosine in longevity: a cohort and Mendelian randomization study |
| Journal: | Aging |
| Published: | 3 Oct 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41045493/ |
| DOI: | https://doi.org/10.18632/aging.206326 |
| URL: | https://www.aging-us.com/article/206326/pdf |
Publication 19299
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Abstract
BACKGROUND: Protein restriction increases lifespan, however, the specific amino acids affecting lifespan are unclear. Tyrosine and its precursor, phenylalanine, may influence lifespan through their response to low-protein diet, with possible sex disparity.</p>
METHODS: We applied cohort study design and Mendelian randomization (MR) analysis. Specifically, we examined the overall and sex-specific relationships between circulating phenylalanine and tyrosine and all-cause mortality in the UK Biobank using Cox regression. To test causality, in two-sample MR analysis, we used genetic variants associated with phenylalanine and tyrosine in UK Biobank with genome-wide significance and uncorrelated (r2 < 0.001) with each other, and applied them to large genome-wide association studies of lifespan, including parental, paternal, and maternal attained ages in the UK Biobank. We also conducted multivariable MR to examine the independent role of phenylalanine and tyrosine.</p>
RESULTS: Tyrosine was associated with shorter lifespan in both observational and MR study, with potential sex disparity. After controlling for phenylalanine using multivariable MR, tyrosine remained related to a shorter lifespan in men (-0.91 years of life, 95% confidence interval (CI) -1.60 to -0.21) but not in women (-0.36 years, 95% CI -0.96 to 0.23). Phenylalanine showed no association with lifespan in either men or women after controlling for tyrosine.</p>
CONCLUSIONS: Reducing tyrosine in people with elevated concentrations may contribute to prolonging lifespan, with potential sex-specific differences. It is worthwhile to explore pathways underlying the sex-specific effects.</p>
13 Keywords
- Aged
- Cohort Studies
- Female
- Genome-Wide Association Study
- Humans
- Longevity
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Phenylalanine
- Polymorphism, Single Nucleotide
- Tyrosine
- United Kingdom
4 Authors
- Jie V Zhao
- Yitang Sun
- Junmeng Zhang
- Kaixiong Ye
1 Application
| Application ID | Title |
|---|---|
| 48818 | Evaluate the causal effects of diet-modifiable biomarkers on clinical outcomes using Mendelian randomization |
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