Taurine Deficiency as a Driver of Aging

Taurine is found to be a driver of aging and its supplementation helps improve lifespan and health span in various animals. It is an interesting molecule to study for human age-related events.

Note: I am excited that the lead researcher Dr. Vijay K. Yadav joined us to discuss his findings on Friday the 2^nd February 2024. Here is the link to his interview on our YouTube channel: https://www.youtube.com/watch?v=tvnPI0qX-Ww

Note before: The Taurine supplementation amount in this study was higher than taken by humans. While 3g/day of Taurine is considered safe, you should consult with a physician to determine whether or not you should start supplementation, as well as the proper dose. I will discuss more about the dosage and safety in another article.

To understand the evidence in this study we need to equip ourselves with following important concepts:

Hallmarks of aging:

1. Aging-induced decline in organ function is marked by several events within the cells that are collectively called “hallmarks of aging.”
2. Some examples of such events are:
   1. Genomic instability.
   2. Deregulated nutrient sensing.
   3. Mitochondrial dysfunction.
   4. Stem cell exhaustion.
   5. Accumulation of senescent cells.
3. Many substances, hormones, and micronutrients reduce in our bodies as we age.
4. An important question to answer is are these changes due to the aging process or are they the actual drivers of the aging process? Researchers have answered this question for Taurine in exquisite detail.

Cellular senescence:

Cellular senescence is defined as a state of permanent cell-cycle arrest. (Reference: https://www.sciencedirect.com/topics/medicine-and-dentistry/cellular-senescence)

1. As we age, we accumulate more senescent cells.
2. Senescent cells release harmful substances collectively called senescent-associated secretory phenotype (SASP).
3. SASP are classified as:
   1. Pro-inflammatory cytokines (IL-1alpha, IL-1beta, IL-6, IL-8).
   2. Chemokines (CXCL-1/3, CXCL-10).
   3. Proteases: including matrix (tissue) remodeling proteins and plasminogen activators.
   4. Growth factors: VEGF, TGF-beta, GM-CSF.
   5. Bioactive lipids: oxidized lipid mediators.
   6. Extracellular vesicles (EVs).
   7. Other.
   8. Reference: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1019313/full

Gene expressions as an indicator of cellular functions:

1. We have a tremendous database of various genes and their functions. mRNA is formed (transcribed) from the open/expressed genes. This mRNA is read by ribosomes, and proteins are created according to the instructions coded on this mRNA (translation.)
2. To understand a cell’s functional state, researchers identify various upregulated or downregulated gene sequences. These genetic expressions are then cross-referenced in the gene function database to understand the state of the function of a cell.

Cellular channels:

Cellular channels are specialized structures present in various cellular membranes. These channels allow a select substances or group of substances to pass across these membranes based on the state of the channel. Taurine also uses a channel to move from outside the cell to inside.

Immune cells increase with age:

In our bodies, circulation and tissues, immune cells increase. These cells potentially create an inflammatory state that results in cell senescence and organ dysfunction. Many chronic diseases are attributable to chronic inflammatory states.

Back to the study.

Dr. Yadav et. Al., first sought to determine if Taurine levels declined with age. Their data demonstrates that as mice, monkeys, and humans age, Taurine levels are reduced. 

The next question was—Are Taurine levels reduced because of aging, or is the reduction in Taurine contributing to the aging process?

Dr. Yadav et. al. supplemented middle aged mice with Taurine to observe the effect on lifespan. They found that the median life span increased by 10-12% and life expectancy at 28 months increased by 18-25%. These results clearly demonstrate that Taurine reduction reduces the lifespan of mice.

Next the researchers sought to understand if the health span of the animals was also changed by Taurine supplementation. Clearly, a longer life with better health is desirable.

For this question Dr. Yadav’s team supplemented middle aged mice with Taurine. When compared to the control cohort, which was not given Taurine, they found that Taurine supplementation creates the following changes:

1. Female mice had better muscle strength, lower body fats (especially in post-menopausal models), better bone density and strength, better control of glucose metabolism, lesser insulin resistance, a lower inflammatory state (immune cells reduced in number), less anxiety, better cognition, and better memory. Food passage through the gastrointestinal tract was also faster, which contributed to a reduction in weight.
2. In female menopause models Taurine supplementation cured osteoporosis and suppressed ovariectomy induced weight gain.
3. In the male mice there was more energy expenditure, more oxygen consumption, more carbon dioxide production, and higher respiratory exchange ratio (RER).
4. Male mice treated with Taurine also showed greater muscle strength, neuromuscular coordination, bone density, glucose tolerance, better memory, and reduced anxiety when compared to control mice.

Clearly the evidence shows that Taurine supplementation in middle aged mice not only increases their lifespan, but also improves their health span.  

The researchers then wanted to understand the cellular mechanisms driven by Taurine in the context of aging. They performed cellular function analysis by looking at the gene expressions in Taurine deprived vs. Taurine supplemented cells. In the deprived cells, they found that six gene signatures (upregulated or downregulated) that were in the pro-aging process.

Taurine also had association with the following age-related outcomes:

1. Taurine suppressed senescent cells. Whether it was due to reduced conversion of young cells to senescent cells or clearance of the senescent cells was not clear.
2. Taurine suppressed adverse consequences of telomerase deficiency. As we age our cells divide either in the natural process of making new cells or during stress and inflammatory states. Each division can cause some cells to have shorter and shorter telomeres. Finally, the cell is unable to divide further and becomes senescent.
3. Taurine suppressed DNA damage and improved survival of the mice after oxidative damage to their DNA.
4. Taurine affected epigenetic changes. However, it increased methylation in some tissues and reduced it in others. Hence, the data isn’t clear on the exact outcome.
5. Taurine modulated nutrient sensing and protein recycling pathways.
6. Reduced the inflammatory cytokines.
7. Improved stem cell renewal.
8. Promoted mitochondrial health.

Researchers found that as humans age, Taurine and its metabolites are reduced in our bodies and is associated with multiple age-associated pathologies. However, soon after exercise Taurine and its metabolites increase in our bloodstream. The significance of this finding is not clear.

Finally, the team demonstrated that Taurine supplementation improves health parameters in middle-aged non-human primates. Monkeys that received Taurine had the following positive outcomes when compared to control cohort:

1. Gained less weight.
2. Fat % tended to be less.
3. Bone density increased.
4. Serum markers of bone formation increased, and the markers for bone resorption reduced.
5. Reduced fasting glucose levels by 19%.
6. Reduced serum concentration of liver damage markers (AST ~36% and ALT 20%).
7. Number of WBCs, monocytes, and granulocytes reduced by ~50%.
8. Mitochondrial health improved.