Perpetual youth is the ultimate dream pursued by human beings, but aging is ubiquitous, unstoppable and irreversible.
Human beings' desire for longevity has existed since ancient times. Qin Shihuang Yingzheng was obsessed with the pursuit of the elixir of life. The construction of the ancient Egyptian pyramids is another form of desire for longevity. Although we are still unable to reach the level of immortality, we have never stopped exploring anti-aging. With the development of science, it may be possible to delay aging. Researchers from all over the world are also committed to the study of aging biology, aiming to discover the driving factors of aging and screen out some potential "elixir medicines", so as to delay aging and improve the quality of life.
As a semi-essential trace amino acid, taurine, the relationship between it and aging has also shown regularity in previous studies. Studies have shown that the concentration of taurine and its metabolites in the body will decrease with age, and exogenous taurine supplementation is beneficial to metabolic and inflammatory diseases[1,2], while the body lacks taurine, It is easy to cause dysfunction of skeletal muscle, retina and central nervous system and the occurrence of aging-related diseases[3,4]. Based on the above-mentioned decline in taurine abundance during aging and its known health effects, Vijay K. Yadav's team from the National Institute of Immunology in India recently published an article in Science entitled "Taurine deficiency as A driver of aging" article, through the variation of taurine content in different species to explore whether taurine deficiency is a driver of aging and affects health lifespan[5].
Let's take a look at the research results~
01 Taurine deficiency is a driver of aging
To comprehensively investigate whether taurine abundance affects healthspan, the researchers measured serum taurine concentrations at different ages in mice, monkeys, and humans and found that serum taurine concentrations were negatively correlated with age (Fig. 1. AC). Supplementing 14-month-old mice with taurine extended the lifespan of these mice (median 10-12%, Fig. 1. D, E). This phenomenon that taurine deficiency may be a driver of aging has not only been verified in mammals, but similar results have also emerged in subsequent studies in nematodes (Fig. 1. F). These results suggest that the effects of taurine on lifespan are the same in invertebrates and mammals.
Figure 1 Taurine deficiency is a driver of aging in different species
02 Supplementation of taurine can prolong the healthy lifespan of wild female mice
Meaningful anti-aging therapies should improve healthy lifespan compared to simply the continuation of lifespan. To assess the effect of taurine supplementation on healthy lifespan, the researchers fed 14-month-old mice with taurine supplementation for 10-12 months, followed by functional assays and tissue analysis to analyze bone, muscle , brain, pancreas, fat, gut and immune system health. Compared with the control group, mice in the taurine-supplemented group had decreased body weight gain (Fig. 2. A, B), increased bone mass (Fig. 2. C), and increased muscle strength (Fig. 2. E, F); tail suspension test , light and dark box test and Y-shaped maze test results showed that the mice in the taurine supplementation group had less depressive behaviors and stronger exploration and curiosity (Fig. 2. G, H); the results of glucose tolerance test and insulin tolerance test showed , the glucose metabolism ability and insulin sensitivity of the mice in the taurine supplemented group were significantly improved (Fig. 2. I), and the gastrointestinal transit speed was faster (Fig. 2. J). In addition, high-dose taurine supplementation ameliorated myeloid leukocyte abnormalities associated with inflammatory states in aging individuals (Fig. 2. K). Based on the above results, taurine supplementation in middle-aged mice can not only improve multiple organ functions, but also prolong their healthy lifespan.
Figure 2 Supplementation of taurine can increase the healthy lifespan of mice
03 Mechanism of Taurine Prolonging Healthy Lifespan
Based on the above findings, the researchers further explored the mechanism by which taurine affects cellular functions to prolong healthy lifespan. Firstly, transcriptome sequencing (RNA Sequencing, RNA-seq) was performed on osteoblasts that can express a large amount of taurine transporter (encoded by Slc6a6) in wild-type and taurine-deficient mice. RNA-seq analysis of osteoblasts from taurine-deficient mice revealed significant differences in pathways such as telomere function, oxidative stress, immune function, protein translation, and stem cell maintenance from wild-type mouse osteoblasts (Fig. 3.A) . In addition, the researchers also constructed a congenital taurine-deficient mouse model (Slc6a6−/−) to explore whether the accumulation of senescent cells induced impairment of healthy lifespan in taurine-deficient mice. Slc6a6−/− mice have a shorter lifespan compared with wild-type mice. The senolytic treatment of Slc6a6−/− mice to clear senescent cells only increased the lifespan of the mice by about 21%. This result shows that taurine also affects factors other than aging (Fig. 3. B).
To further discover the relationship between taurine and other molecular and cellular features of aging. The researchers constructed a telomerase-deficient zebrafish model (Tert-/-) to explore whether taurine affects the deterioration of body health caused by telomerase deficiency. The results showed that about 40% of the fish died within 10 days after fertilization, while Supplementation with taurine significantly increased survival and inhibited the aging process (Fig. 3. CE). Subsequently, a verification experiment based on a mouse model found that taurine supplementation can reduce the abundance of 8-hydroxydeoxyguanosine (8-hydroxydeoxyguanosine, 8-OH-dG) in serum and inhibit DNA damage (Fig. 3. F); The survival rate of mice after injury (Figure 3. G); can affect the methylation pattern, change the chromatin conformation, and then affect the transcriptional changes in the aging process (Figure 3. H); can reduce the liver, brown fat and other tissues The phosphorylation of RS6P maintains protein homeostasis (Figure 3. I); it can reduce the level of pro-inflammatory factors and prevent the pro-inflammatory state produced during aging (Figure 3. J); it can increase the number of resident stem cells, thereby improving a certain The regenerative ability of these tissues (Fig. 3. K); can reduce ROS-induced lipid peroxidation and protein carbonylation, and promote mitochondrial homeostasis (Fig. 3. L).
Based on existing research reports, after cytosolic taurine is transported to mitochondria, it binds to specific uridine residues of tRNALeu to form tm5U-tRNA, tm5U modification is unique to mitochondrial tRNAs, and it can promote the electron transport chain complex Translation of I subunit ND6. The researchers measured whether tm5U-tRNA modification changes during the aging process of mice, and the results showed that compared with the liver of young mice, the tm5U content of tRNAs in the liver of aged mice decreased by more than 60%, while the taurine-supplemented Mice only declined by about 20% (Fig. 3. M). ND6 protein translation levels also showed the same trend, and subsequent worm experiments further suggested that taurine may promote health by increasing the activity of mitochondrial complex I (Fig. 3. N, O).
Figure 3 Modulation of healthspan by taurine is associated with alterations in multiple markers of aging
04 The potential of taurine in primates
To determine whether blood levels of taurine and its metabolites (hypotaurine and N-acetyltaurine) are associated with health variables in humans, the researchers examined the levels of taurine and its metabolites in 11,966 subjects. The association analysis between taurine levels and more than 50 clinical risk factors showed that subjects with higher blood levels of taurine and its related metabolites had lower body mass index (BMI) and lower levels of obesity , a lower prevalence of type 2 diabetes, and lower levels of inflammation (Fig. 4.A). The authors then analyzed serum taurine metabolite concentrations in athletes and sedentary populations to investigate whether taurine levels respond to exercise, an intervention known to improve health. The results showed that the concentrations of taurine and hypotaurine in serum increased after exercise in both the athlete group and the sedentary group (Figure 4. BD), these results indicated that taurine and taurine-related metabolism Increased physical activity may mediate the associated benefits of exercise. Finally, the researchers looked at whether taurine has health and antiaging effects in nonhuman primates by feeding them to aged rhesus monkeys. After 6 months of taurine supplementation, it was found that compared with the control group, the proportion of fat in the supplemented taurine group decreased, the bone density increased, the blood sugar concentration decreased, the concentration of liver injury markers decreased, and the white blood cells and monocytes increased with age. The number of cells and granulocytes decreased, the concentration of 8-OH-dG, an indirect marker of ROS-induced molecular damage, and the concentration of lipid peroxides and protein carbonyl groups decreased (Figure 4. EO).
Figure 4 Taurine pathway affects primate healthspan
Overall, the above results show that taurine concentration decreases with the aging process, and taurine supplementation can inhibit this decline and increase the health lifespan of different species, which also determines that taurine deficiency is the cause of aging in these species. The driving factors, and supplementing taurine can be used as a potential therapeutic strategy to delay aging. If it is to be applied in the clinic, further randomized controlled clinical trials are still needed to evaluate the anti-aging effect of taurine.
epilogue
As the basic constituent unit of the basic protein group of living matter, amino acids play a vital role in the growth and development of living organisms, and the relationship between various types of amino acids and aging has also attracted the attention of researchers. In addition to the significant link between taurine and the aging process shown in this study, previous studies have reported that restricting dietary methionine and branched chain amino acids (Branched chain amino acid, BCAA) can improve insulin resistance, increased oxidative stress, etc. Aging hallmark phenomenon [6]. In March of this year, the team of Zhang Jie and Leng Lige of Xiamen University found that supplementing D-serine can promote the expression of Menin protein in the hypothalamus, help improve the metabolic homeostasis of the body, and thus hinder the acceleration of the aging process [7]. Therefore, understanding the concentration changes of various amino acids in organisms can effectively monitor the physiological and pathological states of organisms.