16 Jun 2023

Should older adults add taurine to their diets? Perhaps, suggest researchers led by Vijay Yadav, Columbia University, New York. In the June 9 Science, they reported that a person’s ability to make this amino acid declines steeply with age. Serum levels in 60-year-olds are 80 percent lower than those in children. Feeding the amino acid to middle-aged mice increased their lifespan by a few months and improved their memories. It also reduced inflammatory markers and many other signs of aging in mice and in monkeys. “These are very impressive effects on the mouse lifespan, and the improved health parameters in monkeys are stunning,” Andrew Dillin, University of California, Berkeley, wrote to Alzforum. “Why did the field miss this seemingly obvious amino acid deficiency?”

Taurine and Aging. Supplementing their chow with taurine extends mouse lifespan (bottom left), improves organ function, and reduces cellular signs of aging (middle). Taurine deficiency is tied to multiple health problems in people (top right), but large-scale trials testing its beneits have yet to be done (bottom right). [Courtesy of Singh et al., Science, 2023.]

Taurine, considered a nonessential amino acid, carries a reactive amine and a sulfonic, rather than a carboxylic, acid. Scientist believe it functions as an antioxidant, by neutralizing the reactive oxygen species hypochlorite to form the antioxidant N-chlorotaurine. It can also be broken down into hydrogen sulfide, another ROS scavenger. Other potential roles are to activate GABA and glycine receptors, or to improve the fidelity of mitochondrial protein synthesis. Small clinical studies of adults taking the amino acid in supplement form have suggested that it eases symptoms of metabolic and inflammatory diseases, such as Type 2 diabetes, heart failure, and neurodevelopmental disorders (Jong et al., 2021; Caine and Geracioti, 2016). Could taurine also influence aging?

To find out, co-first authors Parminder Singh in the National Institute of  Immunology in New Delhi, where Yadav has a second appointment, and Kishore Gollapalli in New York measured concentrations of the amino acid in blood samples from 80 people ages 1 to 65 from the Kuopio Ischaemic Heart Disease Risk Factor Study, Finland, or from Kocaeli University Hospital, Turkey. Serum taurine concentration inversely correlated with age. Middle-aged people had 80 percent less than did children. Ditto for 56-week-old versus 4-week-old wild-type mice, and 15-year-old versus 5-year-old rhesus macaques (see image below).

Waning with Age. Serum taurine declines with age in people (left), mice (middle), and rhesus monkeys (right). [Courtesy of Singh et al., Science, 2023.]

Would boosting taurine levels in older animals slow aging? The researchers first turned to mice, feeding 14-month-olds 1,000 mg per kg taurine daily. This raised blood taurine close to levels seen in 4-week-old mice. Compared to controls, taurine-fed mice lived for 11 percent longer, or about two months. They also grew bigger and stronger bones, clung to a wire and ran on a rotarod for longer, and more often ambled among the arms of a Y maze, a sign of better memory. Other signs of attenuated aging include fewer inflammatory cytokines, less oxidative DNA damage, and fewer reactive oxygen species in muscle, a sign of better mitochondrial health.

The anti-aging effects extended to 15-year-old rhesus macaques fed the mouse-equivalent dose of 250 mg per kg. Compared to controls, the treated animals had stronger bones, less oxidative damage, and fewer inflammatory immune cells in their blood.

“These broad anti-aging effects are reminiscent of the effects of caloric restriction,” noted Mark Mattson of Johns Hopkins University in Baltimore. Along these lines, treated mice and monkeys weighed less and carried less body fat than controls, despite eating the same amount of chow. “Perhaps taurine affects energy metabolism in a way similar to caloric restriction,” Mattson speculated.

Singh and colleagues also uncovered links between serum taurine and human health. Among 12,000 people, average age 60, from the EPIC-Norfolk cohort, a prospective epidemiology study of cancer led by scientists at the University of Cambridge, U.K., those with high blood taurine had a lower body mass index and carried less fat around their midsection than people with low blood taurine. They also were less likely to have Type 2 diabetes, had lower average blood glucose levels, and had less of the inflammatory marker C-reactive protein in their blood.

Should you grab a bottle of taurine supplements or add more taurine-rich foods, such as seafood and meat, to your diet? Diet alone is unlikely to cut the mustard, since young adult vegans, who consume almost none, have only 20 percent less taurine in their blood than non-vegans (Laidlaw et al., 1988; Rana and Sanders, 1986; Elshorbagy et al., 2017). “Boosting levels to the point of altering biology likely requires a critical amount of supplementation,” noted Russell Swerdlow of Kansas University Medical Center (comment below). Despite it being a naturally occurring amino acid with no known toxic effects, Joseph McGaunn and Joseph Baur at the University of Pennsylvania, Philadelphia, caution against supplements. “Potential risks still warrant consideration because large, long-term human safety trials are lacking, and the equivalent doses used in the study would be very high in humans,” they wrote in a Science editorial. They recommend testing the amino acid in clinical trials.

Taurine is not to be confused with homotaurine, aka tramiprosate, which has one additional carbon molecule between the two reactive groups. It was tested in clinical trials for Alzheimer’s since it purportedly prevents aggregation of Aβ and even ApoE (Nemergut et al., 2023). Trials of a derivative, ALZ-801, are ongoing.—Chelsea Weidman Burke

Comments

1. • Mark Mattson
     Johns Hopkins
   • Posted: 16 Jun 2023

   The findings are remarkable in that the authors report beneficial effects of taurine on the health/function of multiple organ systems. These broad anti-aging effects are reminiscent of the effects of caloric restriction. Indeed, a caveat of the study is that the body weights of mice in the taurine group were significantly lower than those in the control group. This suggests that many, or all, of the effects of taurine may be attributed to caloric restriction. Perhaps taurine suppresses appetite or affects energy metabolism in a similar way.

   View all comments by Mark Mattson
2. • Russell Swerdlow
     University of Kansas
   • Posted: 16 Jun 2023

   There are a few take-home messages from this paper for me, none of which are particularly surprising. The first is that supplementing an organism with a biological intermediate can directly or indirectly affect a metabolic flux, or fluxes, to influence basic biology (Swerdlow, 2014). We know this from studies of other biological pathway intermediates (Wilkins et al., 2014; Vidoni et al., 2020). The second message is that boosting levels to the point of altering biology likely requires a critical amount of supplementation (Vidoni et al., 2020). 

   While some of the biochemical consequences of biological intermediate-boosting are to some extent predictable, the big-picture biological effects are more complex (Swerdlow, 2014). That is one reason studies such as this are important.

   Again, it is not surprising a study found large amounts of taurine supplementation affected organism biology. After all, from a strict biochemical and molecular level, what we think of as life is arguably the sum total of the metabolic fluxes that play out within a definable unit, and those fluxes are modifiable through recognized biochemical principles such as the law of mass action (Swerdlow, 2014). It will be interesting to see whether other studies conclude taurine supplementation benefits organism health and well-being, and ultimately human health and well-being. Finally, it is worth pointing out that homotaurine (tramiprosate) was previously considered for the treatment of AD.

   Overall, data from this paper do support the abstract’s final statement—human trials will be necessary to determine if taurine slows aging and its associated biological changes. Based on the current study, proving or disproving this outcome is not a crazy idea.

   References:

   Swerdlow RH. Bioenergetic medicine. Br J Pharmacol. 2014 Apr;171(8):1854-69. PubMed.

   Wilkins HM, Harris JL, Carl SM, E L, Lu J, Eva Selfridge J, Roy N, Hutfles L, Koppel S, Morris J, Burns JM, Michaelis ML, Michaelis EK, Brooks WM, Swerdlow RH. Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis. Hum Mol Genet. 2014 Dec 15;23(24):6528-41. Epub 2014 Jul 15 PubMed.

   Vidoni ED, Choi IY, Lee P, Reed G, Zhang N, Pleen J, Mahnken JD, Clutton J, Becker A, Sherry E, Bothwell R, Anderson H, Harris RA, Brooks W, Wilkins HM, Mosconi L, Burns JM, Swerdlow RH. Safety and target engagement profile of two oxaloacetate doses in Alzheimer's patients. Alzheimers Dement. 2021 Jan;17(1):7-17. Epub 2020 Jul 27 PubMed.

   View all comments by Russell Swerdlow

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References

Therapeutics Citations

1. Alzhemed™
2. ALZ-801

Paper Citations

1. Jong CJ, Sandal P, Schaffer SW. The Role of Taurine in Mitochondria Health: More Than Just an Antioxidant. Molecules. 2021 Aug 13;26(16) PubMed.
2. Caine JJ, Geracioti TD. Taurine, energy drinks, and neuroendocrine effects. Cleve Clin J Med. 2016 Dec;83(12):895-904. PubMed.
3. Laidlaw SA, Shultz TD, Cecchino JT, Kopple JD. Plasma and urine taurine levels in vegans. Am J Clin Nutr. 1988 Apr;47(4):660-3. PubMed.
4. Rana SK, Sanders TA. Taurine concentrations in the diet, plasma, urine and breast milk of vegans compared with omnivores. Br J Nutr. 1986 Jul;56(1):17-27. PubMed.
5. Elshorbagy A, Jernerén F, Basta M, Basta C, Turner C, Khaled M, Refsum H. Amino acid changes during transition to a vegan diet supplemented with fish in healthy humans. Eur J Nutr. 2017 Aug;56(5):1953-1962. Epub 2016 Jun 11 PubMed.
6. Nemergut M, Marques SM, Uhrik L, Vanova T, Nezvedova M, Gadara DC, Jha D, Tulis J, Novakova V, Planas-Iglesias J, Kunka A, Legrand A, Hribkova H, Pospisilova V, Sedmik J, Raska J, Prokop Z, Damborsky J, Bohaciakova D, Spacil Z, Hernychova L, Bednar D, Marek M. Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer's Disease drug candidate. Mol Neurodegener. 2023 Jun 6;18(1):38. PubMed.

Further Reading

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