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SRT2104

SRT2104

The sirtuin family of proteins (SIRT1-7) possesses a unique ability that is integral not only in human metabolism, but also in the field of anti-aging and lifespan regulation. Specifically, activation of sirtuin (silent mating type information regulation 2 homolog) 1, or SIRT1, are being studied for their role in the treatment of age-related, chronic, debilitating metabolic diseases such as diabetes, obesity, and cancer. In fact, SRT2104, a selective activator of SIRT1, has been shown to exert significant health benefits on a wide array of medical maladies.

Overall Health Benefits of SIRT2104

  • Improves cardiovascular health [1-7]
  • Improves lipid profile [8-10]
  • Fights inflammation [11-16]
  • Improves blood sugar levels [17-22]
  • Improves bone health [23-27]

Proven Health Benefits of SIRT2104

Improves Cardiovascular Health

SRT2104 has cardioprotective effects that can help extend the lifespan of people with different heart diseases. Studies suggest that SRT2104 exerts these beneficial effects through various important mechanisms:

  1. In adults with type 2 diabetes mellitus, oral SRT2104 (2.0 g/day) administration for 28 days improved function of the blood vessels of the heart and decreased blood clot formation. [1]
  2. In diabetic mice, SRT2104 reduced aortic endothelial dysfunction. [2]
  3. In both type 2 diabetes mellitus patients and healthy cigarette smokers, SRT2104 administration at 2.0 g once daily for 28 days improved cardiac blood vessel function. [3]
  4. In mice, administration of SRT2104 improved blood flow to the heart by inducing dilation of the blood vessels. [4]
  5. In mice with atherosclerosis, a condition characterized by deposition of plaques of fatty material on the inner walls of the arteries of the heart, SRT2104 administration reduced macrophage foam cell formation – a process that can contribute to plaque build-up. [5]
  6. A mice study found that inhibition of SIRT1 is associated with increased blood clot formation, suggesting that SRT2104, a selective activator of SIRT1, can potentially reduce the risk of blood clots in the heart. [6]
  7. In healthy cigarette smokers and subjects with type 2 diabetes mellitus, administration of SRT2104 reduced arterial stiffness. [7]

Improves Lipid Profile

Several studies show that SRT2104 also has the ability to reduce the levels of lipids such as low-density lipoprotein (bad cholesterol) and triglycerides:

  1. In healthy cigarette smokers, administration of SRT2104 decreased serum total cholesterol, low‐density lipoprotein cholesterol, and triglyceride concentrations. [8]
  2. In elderly volunteers, oral doses of 0.5 or 2.0 g SRT2104 decreased low-density lipoprotein and triglyceride levels after 28 days of treatment. [9]
  3. In diabetic subjects, administration of SRT2104 at doses of 250, 500, 1,000 and 2,000 mg reduced lipid levels. [10]

Fights Inflammation

There’s strong scientific evidence suggesting that SRT2104 has potent anti-inflammatory properties which can be beneficial in a broad range of debilitating inflammatory conditions:

  1. In healthy volunteers, 2000 mg of SRT2104 reduced LPS-induced release of inflammatory substances such as IL-6 and IL-8. [11]
  2. In patients with mild-to-moderate ulcerative colitis, administration of SRT2104 at doses of 50 mg or 500 mg daily, significantly reduced fecal calprotectin, a biomarker of colitis disease activity. [12-13]
  3. In patients with moderate-to-severe psoriasis, SRT2104 administration once daily for 12 weeks at 250, 500 and 1000 mg improved Psoriasis Area and Severity Index (PASI) scores and decreased the levels of genes associated with the disease. [14]
  4. In healthy volunteers, single and repeated administration of SRT2104 reduced lipopolysaccharide-induced release of the cytokines interleukin-6 and interleukin-8. [15]
  5. A cell study also found that SIRT1 activity is decreased in lesional skin of patients with psoriasis, suggesting that SRT2104 may help reduce the risk of this autoimmune disease. [16]

Improves Blood Sugar Levels

Evidence also suggests that SRT2104 may help reduce elevated blood sugar levels in diabetic patients:

  1. In obese diabetic patients, SRT2104 administration reduced blood sugar levels, liver fat, and blood pressure. [17]
  2. A study found that SRT2104 exerts its anti-diabetic effects by modulating various metabolic pathways, including blood sugar metabolism. [18]
  3. In diet-induced obese and genetically obese mice, SRT2104 improved insulin sensitivity, reduced blood sugar levels, and increased mitochondrial capacity. [19]
  4. In diabetic subjects, administration of SRT2104 at doses of 250, 500, 1,000 and 2,000 mg once daily for 28 days also reduced blood sugar levels. [10]
  5. In diet-induced obese mice, oral treatment with SRT2104 for 12 weeks improved both metabolic function and blood sugar homeostasis. [20]
  6. In obese mice, SRT2104 ameliorated insulin resistance by increasing energy expenditure via enhancement of carbohydrate and fatty acid oxidation. [21]
  7. A study also found that SRT2104-induced activation of SIRT1 can improve insulin sensitivity, resulting in reduced blood sugar levels. [22]

Improves Bone Health

Numerous body of research also shows that SRT2104-induced activation of SIRT1 can unlock beneficial effects on bone health:

  1. In male mice on a standard diet, addition of SRT2104 preserved bone and muscle mass. [23]
  2. In SIRT1-deficient mice, a significant reduction in cortical bone thickness is observed, suggesting that SRT2104 may help slow progression of bone loss. [24-25]
  3. Mice studies have also shown that sirtuin family of proteins can help combat osteoporosis and ovariectomy-induced bone loss. [26-27]

References:

  1. Available from https://openheart.bmj.com/content/4/2/e000647
  2. Wu H, Wu J, Zhou S, et al. SRT2104 attenuates diabetes-induced aortic endothelial dysfunction via inhibition of P53. J Endocrinol. 2018;237(1):1-14.
  3. Available from https://clinicaltrials.gov/ct2/show/NCT01031108
  4. Available from https://www.pnas.org/content/104/37/14855?ijkey=9b8d33a7d87b2cbaecdb95665dc7751bf27fee94&keytype2=tf_ipsecsha
  5. Stein S, Lohmann C, Schäfer N, et al. SIRT1 decreases Lox-1-mediated foam cell formation in atherogenesis. Eur Heart J. 2010;31(18):2301-9.
  6. Breitenstein A, Stein S, Holy EW, et al. Sirt1 inhibition promotes in vivo arterial thrombosis and tissue factor expression in stimulated cells. Cardiovasc Res. 2011;89(2):464-72.
  7. Available from https://openheart.bmj.com/content/3/1/e000402
  8. Venkatasubramanian S, Noh RM, Daga S, et al. Cardiovascular effects of a novel SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers. J Am Heart Assoc. 2013;2(3):e000042.
  9. Libri V, Brown AP, Gambarota G, et al. A pilot randomized, placebo controlled, double blind phase I trial of the novel SIRT1 activator SRT2104 in elderly volunteers. PLoS ONE. 2012;7(12):e51395.
  10. Baksi A, Kraydashenko O, Zalevkaya A, Stets R, Elliott P, Haddad J, Hoffmann E, Vlasuk GP, Jacobson EW. A phase II, randomized, placebo-controlled, double-blind, multi-dose study of SRT2104, a SIRT1 activator, in subjects with type 2 diabetes. Br J Clin Pharmacol. 2014;78:69–77.
  11. van der Meer AJ, Scicluna BP, Moerland PD, Lin J, Jacobson EW, Vlasuk GP, van der Poll T. The Selective Sirtuin 1 Activator SRT2104 Reduces Endotoxin-Induced Cytokine Release and Coagulation Activation in Humans. Critical care medicine. 2015;43:e199–202.
  12. Sands BE, Joshi S, Haddad J, Freudenberg JM, Oommen DE, Hoffmann E, McCallum SW, Jacobson E. Assessing Colonic Exposure, Safety, and Clinical Activity of SRT2104, a Novel Oral SIRT1 Activator, in Patients with Mild to Moderate Ulcerative Colitis. Inflammatory bowel diseases. 2016;22:607–614.
  13. Available from https://clinicaltrials.gov/ct2/history/NCT01453491?V_13=View
  14. Krueger JG, Suarez-Farinas M, Cueto I, Khacherian A, Matheson R, Parish LC, Leonardi C, Shortino D, Gupta A, Haddad J, Vlasuk GP, Jacobson EW. A Randomized, Placebo-Controlled Study of SRT2104, a SIRT1 Activator, in Patients with Moderate to Severe Psoriasis. PLoS One. 2015;10:e0142081.
  15. Van der meer AJ, Scicluna BP, Moerland PD, et al. The Selective Sirtuin 1 Activator SRT2104 Reduces Endotoxin-Induced Cytokine Release and Coagulation Activation in Humans. Crit Care Med. 2015;43(6):e199-202.
  16. Becatti M, Barygina V, Emmi G, et al. SIRT1 activity is decreased in lesional psoriatic skin. Intern Emerg Med. 2016;11(6):891-3.
  17. Available from http://blogs.nature.com/spoonful/2011/11/small_resveratrol_trial_shows_1.html
  18. Available from https://medkoo.com/products/5855
  19. Milne JC, Lambert PD, Schenk S, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007;450(7170):712-6.
  20. Qi Y, Davis ML, Hirsch ML, Cote AM, Lainez EO, Johnson MO, Gagne DJ, Vlasuk GP, Ellis JL. Activation of sirtuin1 (SIRT1) by the novel small molecule SRT2104 promotes body weight loss, increases exercise capacity and improves insulin sensitivity in diet-induced obese mice. Diabetes. 2010;59(Suppl. 1) 390-PP.
  21. Qi Y, Davis ML, Lainez EO, Cote AM, Johnson MO, Gagne DJ, Vlasuk GP, Ellis JL, Suri V. SRT2104, a novel small molecule SIRT1 activator ameliorates insulin resistance and promotes glucose utilization measured under a hyperinsulinemic-euglycemic clamp by enhancing both glycolysis and carbohydrate oxidation in mice fed a high fat diet. Diabetes. 2011;60(Suppl. 1) 1007-P.
  22. Elliott PJ, Jirousek M. Sirtuins: novel targets for metabolic disease. Curr Opin Investig Drugs. 2008;9(4):371-8.
  23. Mercken EM, Mitchell SJ, Martin-Montalvo A, et al. SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass. Aging Cell. 2014;13(5):787–796. doi:10.1111/acel.12220.
  24. Cohen-kfir E, Artsi H, Levin A, et al. Sirt1 is a regulator of bone mass and a repressor of Sost encoding for sclerostin, a bone formation inhibitor. Endocrinology. 2011;152(12):4514-24.
  25. Edwards JR, Perrien DS, Fleming N, et al. Silent information regulator (Sir)T1 inhibits NF-κB signaling to maintain normal skeletal remodeling. J Bone Miner Res. 2013;28(4):960-9.
  26. Artsi H, Cohen-kfir E, Gurt I, et al. The Sirtuin1 activator SRT3025 down-regulates sclerostin and rescues ovariectomy-induced bone loss and biomechanical deterioration in female mice. Endocrinology. 2014;155(9):3508-15.
  27. Zainabadi K, Liu CJ, Caldwell ALM, Guarente L. SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis. PLoS ONE. 2017;12(9):e0185236.

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