Higher Tyrosine Levels Linked to Shorter Lifespan in Men, Study Finds

A new study published in the journal Aging suggests that higher circulating levels of the amino acid tyrosine may be associated with a shorter lifespan, with the most pronounced evidence observed in men. Researchers from the University of Hong Kong and the University of Georgia utilized data from 272,475 UK Biobank participants to examine the relationship between circulating amino acids and all-cause mortality. By combining cohort analysis with Mendelian randomization, the team sought to determine if these nutrients could partially explain the well-documented longevity gap between men and women.

The findings indicate that while circulating phenylalanine is linked to increased mortality risk in both sexes, tyrosine shows a specific, positive association with all-cause mortality in men. Although the researchers noted that the difference between the sexes was not statistically significant in all models, the genetic evidence consistently pointed toward higher tyrosine levels being associated with shorter lifespans. The study highlights that while these amino acids are modifiable through diet, the current findings do not establish a direct causal link between dietary intake and longevity, nor do they support the long-term use of tyrosine supplements for life extension.

Biological sex is a primary determinant of life expectancy, with men consistently living shorter lives than women. Researchers have long sought to understand the metabolic underpinnings of this disparity. Tyrosine, which is synthesized from phenylalanine, plays a critical role in the production of neurotransmitters like dopamine and norepinephrine. These chemicals are essential for regulating stress responses and cognitive function, both of which are deeply tied to metabolic health.

Previous animal studies have shown that protein restriction can extend lifespan, leading scientists to hypothesize that circulating amino acid levels are key mediators. In the current study, the researchers examined whether the sex-specific differences in tyrosine levels—which are typically lower in young women than in young men—could be a factor in the observed longevity gap. By using parental attained age as a genetic proxy for lifespan, the team aimed to strengthen the causal inference behind these associations.

The analysis of the UK Biobank cohort revealed distinct patterns for the two amino acids. Circulating phenylalanine was found to be positively associated with all-cause mortality in both men and women, with specific links to cardiovascular and cancer-related deaths. In contrast, the association between tyrosine and mortality was more sex-dependent, showing a clearer link to shorter lifespans in men.

When the researchers controlled for phenylalanine, the association between tyrosine and reduced lifespan remained evident in men, while findings in women were less consistent. The study suggests that the non-linear nature of these associations means the risks are likely more applicable to individuals who already possess higher baseline levels of these amino acids. The researchers emphasized that these results do not suggest that tyrosine is inherently toxic, but rather that its regulation within the body is a complex factor in long-term health.

While the study does not definitively prove how tyrosine influences lifespan, the authors point to insulin resistance as a primary candidate for the underlying mechanism. Tyrosine-mediated insulin resistance is known to increase the risk of chronic diseases, and its effects can be modulated by sex hormones such as testosterone. Because testosterone is associated with survival and has a more pronounced effect in men, the interaction between this hormone and tyrosine-derived neurotransmitters may explain the sex-specific findings.

the authors note that experimental evidence from calorie restriction studies shows sex-specific effects on metabolic health. The study authors cautioned that their work does not test dietary interventions in humans, and circulating levels of amino acids do not necessarily reflect direct dietary intake. Consequently, while the study provides a new perspective on metabolic longevity, it does not provide a roadmap for dietary changes or supplementation strategies at this time.

The study acknowledges several limitations, most notably the potential for bias due to sample overlap when using genetic variants from the UK Biobank for both the amino acid and lifespan analyses. To address this, the team conducted sensitivity analyses using genetic data from separate genome-wide association studies, which yielded broadly consistent results. However, the researchers stress that further validation in diverse populations is necessary.

Looking ahead, the authors suggest that future studies should focus on the biological pathways connecting amino acid metabolism to specific disease outcomes. Because the study did not evaluate the long-term use of tyrosine supplements—often marketed for mood enhancement—the researchers explicitly stated that their findings do not support the use of such supplements for longevity benefits. The study serves as a foundational step in understanding how specific nutrients might contribute to the complex, sex-specific landscape of human aging.