A protein is a sequence of amino acids joined together to form a single molecule, and consequently amino acids are everywhere in our biochemistry. Their presence influences many processes, and the complexity of cellular biochemistry continues to ensure that relatively little of this is anywhere near completely mapped. Circulating amino acid levels, as measured in blood samples, have received more attention in the context of aging and longevity in recent years. There are a few hundred different amino acids beyond the twenty used to manufacture proteins, some of which must be obtained via diet as they are not synthesized by our biochemistry. Researchers have found a number of associations between specific amino acid levels and aging, as well as demonstrating that supplementation or restriction of specific dietary amino acids can modestly influence the pace of aging in animal studies.
In today's open access paper, researchers demonstrate a small effect on male lifespan emerging from epidemiological data on tyrosine levels. The underlying mechanisms remain to be discovered, but this sort of study is intended as a prompt for others to dig into what might be happening under the hood. The authors of this paper speculate on mechanisms, but it is just speculation at this point. Tyrosine is not an essential amino acid, but is synthesized from the essential amino acid phenylalanine and so its availability in the body is still effectively constrained by diet. Phenylalanine restriction has not been shown to produce benefits in the way that restriction of some other essential amino acids does, and in fact severe restriction causes neurological issues if intake is sustained at very low levels.
The role of phenylalanine and tyrosine in longevity: a cohort and Mendelian randomization study
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. 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 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.
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) but not in women. Phenylalanine showed no association with lifespan in either men or women after controlling for tyrosine.
Based on our results, targeting tyrosine may be a potential strategy for improving lifespan. Partly consistent with our findings, animal experiment suggests that restricting dietary protein in rats extends lifespan while lowering tyrosine concentrations in liver and muscle. The biological processes linking tyrosine to lifespan have not been thoroughly determined. Tyrosine was associated with insulin resistance. According to evolutionary biology, more investment in growth and reproduction often comes at the expense of lifespan, while insulin acts as one of the key regulators of growth and reproduction. Consistently, insulin resistance has been shown to be related to multiple diseases and decreased lifespan. Insulin resistance may also have sex-specific effects.
View the full article at FightAging
