Russian Journal of Biological Physics and Chemisrty Russian Journal of Biological Physics and Chemisrty АКТУАЛЬНЫЕ ВОПРОСЫ БИОЛОГИЧЕСКОЙ ФИЗИКИ И ХИМИИ 2499-9962 54522 МЕДИЦИНСКАЯ БИОФИЗИКА И БИОФИЗИЧЕСКАЯ ХИМИЯ MEDICAL BIOPHYSICS AND BIOPHYSICAL CHEMISTRY МЕДИЦИНСКАЯ БИОФИЗИКА И БИОФИЗИЧЕСКАЯ ХИМИЯ The mechanism of action of preparations of PULDIS energet R and PULDIS herpoff K on energy and their role in the prevention of aging and age-related diseases Механизм действия препаратов ПУЛДИС энергет Р и ПУЛДИС герпофф К на энергетику и их роль в профилактике старения и возраст-зависимых болезней Касумов Э А Kasumov E A kasumov_eldar@mail.ru Касумов Р Э Kasumov R E Касумова И В Kasumova I V Научно-производственный центр «КОРВЕТ» ru Research and Production Center «KORVET» ru Научно-производственный центр «КОРВЕТ» ru Research and Production Center «KORVET» ru Научно-производственный центр «КОРВЕТ» ru Research and Production Center «KORVET» ru 25 06 2020 25 06 2020 5 2 278 285 20 06 2020 20 06 2020 https://rusjbpc.ru/en/nauka/article/54522/view

Несмотря на усилия ученых проблемы преждевременного старения, а также болезней таких, как рак, диабет, опоясывающий герпес, остеопороз и других до сих пор остаются нерешенными. Соединения гуанидина оказывают сильное действие на эти процессы. Согласно, нами разработанному механо-хемиосмотическому механизму, трансформация энергии как при синтезе, так и при гидролизе АТФ происходит при прямом участии аминокислотных остатков аргинина (физиологического соединения гуанидина) и лизина. Кроме того, аргинин и лизин участвуют во многих процессах в метаболизме клетки. Поскольку аргинин в организме синтезируется до 28-30 лет, мы считаем, что старение начинается с уменьшением синтеза аргинина. После этого возраста необходимо поддерживать содержание аргинина в организме принимая его экзогенно, а содержание лизина - незаменимой аминокислоты, должно пополняться постоянно. С этой целью нами разработаны и зарегистрированы биологически активные добавки - препараты ПУЛДИС энергет Р и ПУЛДИС герпофф К, содержащие L-аргинин и L-лизин, соответственно. В связи с этим предлагаем рецепт здорового долголетия.

Despite the efforts of scientists, the problems of premature aging, as well as diseases such as cancer, diabetes, herpes zoster, osteoporosis, and others still remain unresolved. Guanidine compounds have a strong effect on these processes. According to the mechano-chemiosmotic mechanism we have developed, energy transformation both in the synthesis and in the hydrolysis of ATP occurs with the direct participation of amino acid residues of arginine (a physiological compound of guanidine) and lysine. In addition, arginine and lysine are involved in many processes in the cell metabolism. Since arginine in the body is synthesized up to 28-30 years, we believe that aging begins with a decrease in arginine synthesis. After this age, it is necessary to maintain the arginine content in the organism by taking it exogenously, and the lysine content of an essential amino acid must be constantly replenished. For this purpose, we have developed and registered biologically active additives - the PULDIS energet R and PULDIS herpoff K preparations, containing L-arginine and L-lysine, respectively. In this regard, we offer a recipe for healthy longevity.

 механо-хемиосмотический механизм старение болезнь лизин аргинин mechano-chemiosmotic mechanism aging disease arginine lysine

Lopez-Lazaro M. The Warburg effect: why and how do cancer cells activate glycolysis in the presence of oxygen? Anticancer Agents Med. Chem. journal, 2008, vol. 8, no. 3, pp. 305-312, DOI: 10.2174/187152008783961932. Lopez-Lazaro M. The Warburg effect: why and how do cancer cells activate glycolysis in the presence of oxygen? Anticancer Agents Med. Chem. journal, 2008, vol. 8, no. 3, pp. 305-312, DOI: 10.2174/187152008783961932. Giang A-H., Raymond T., Brookes P., Bentley K.M., Schwarz E., O’Keefe R., Eliseev R. Mitochondrial dysfunction and permeability transition in osteosarcoma cells showing the Warburg effect. J Biol Chem., 2013, vol. 288, no. 46, pp. 33303-33311, DOI: 10.1074/jbc.M113.507129. Giang A-H., Raymond T., Brookes P., Bentley K.M., Schwarz E., O’Keefe R., Eliseev R. Mitochondrial dysfunction and permeability transition in osteosarcoma cells showing the Warburg effect. J Biol Chem., 2013, vol. 288, no. 46, pp. 33303-33311, DOI: 10.1074/jbc.M113.507129. Vays V.B., Eldarov Ch.V., Vangely I.V., Kolosova N.G., Bakeeva L.E., Skulachev V.P. Antioxidant SkQ1 delays sarcopenia-associated damage of mitochondrial ultrastructure. Aging (Albany N.Y.), 2014, vol. 6, no. 2, 140-148, DOI: 10.18632/aging.100636. Vays V.B., Eldarov Ch.V., Vangely I.V., Kolosova N.G., Bakeeva L.E., Skulachev V.P. Antioxidant SkQ1 delays sarcopenia-associated damage of mitochondrial ultrastructure. Aging (Albany N.Y.), 2014, vol. 6, no. 2, 140-148, DOI: 10.18632/aging.100636. Yu L.M., Zhang W.H., Han X.X., Li Y.Y., Lu Y. et al. Hypoxia-Induced ROS Contribute to Myoblast Pyroptosis during Obstructive Sleep Apnea via the NF-κB/HIF-1α Signaling Pathway. Oxid Med Cell Longev., 2019, pp. 1-19, DOI: 10.1155/2019/4596368. Yu L.M., Zhang W.H., Han X.X., Li Y.Y., Lu Y. et al. Hypoxia-Induced ROS Contribute to Myoblast Pyroptosis during Obstructive Sleep Apnea via the NF-κB/HIF-1α Signaling Pathway. Oxid Med Cell Longev., 2019, pp. 1-19, DOI: 10.1155/2019/4596368. Heß V., Kasim M., Mathia S., Persson P.B., Rosenberger Ch., Fähling M. Episodic Hypoxia Promotes Defence Against Cellular Stress. Cell Physiol Biochem., 2019, vol. 52, pp. 1075-1091, DOI: 10.33594/000000073. Heß V., Kasim M., Mathia S., Persson P.B., Rosenberger Ch., Fähling M. Episodic Hypoxia Promotes Defence Against Cellular Stress. Cell Physiol Biochem., 2019, vol. 52, pp. 1075-1091, DOI: 10.33594/000000073. Сапрунова В.Б., Солодовнокова И.М., Бакеева Л.Е. Выявление цитохром с-оксидазной активности в митохондриях кардиимицитов изолированной ткани миокарда при длительном действии гипоксии. Цитология, 2008, т. 50, № 3, c. 268-274. @@[Saprunova V.B., Solodovnikova I.M., Bakeeva L.E. The cytochrome c oxidase activity in mitochondria of cardiomyocytes of isolated cardiac tissue underlong-termhypoxic incubation. Tsitologiia, 2008, vol. 50, no. 3, pp. 268-274. (In Russ.)] Saprunova V.B., Solodovnokova I.M., Bakeeva L.E. Vyyavlenie citohrom s-oksidaznoy aktivnosti v mitohondriyah kardiimicitov izolirovannoy tkani miokarda pri dlitel'nom deystvii gipoksii. Citologiya, 2008, t. 50, № 3, c. 268-274. @@[Saprunova V.B., Solodovnikova I.M., Bakeeva L.E. The cytochrome c oxidase activity in mitochondria of cardiomyocytes of isolated cardiac tissue underlong-termhypoxic incubation. Tsitologiia, 2008, vol. 50, no. 3, pp. 268-274. (In Russ.)] Vartapetian B.B., Andreeva I.N., Generozova I.P., Polyakova L.I., Maslova I.P., Dolgikh Y.I., Stepanova A.Y. Functional electron microscopy in studies of plant response and adaptation to anaerobic stress. Ann Bot., 2003, no. 91, pp. 155-172. Vartapetian B.B., Andreeva I.N., Generozova I.P., Polyakova L.I., Maslova I.P., Dolgikh Y.I., Stepanova A.Y. Functional electron microscopy in studies of plant response and adaptation to anaerobic stress. Ann Bot., 2003, no. 91, pp. 155-172. Kasumov E.A., Zaitseva M.G., Kasumova I.V., Senakhova M.A. Effect of valinomycin on respiration, changes of medium pH, and volume in mitochondria from mung bean hypocotyls. Russian plant physiology, 1993, vol. 40, no. 3, pp. 375-380. Kasumov E.A., Zaitseva M.G., Kasumova I.V., Senakhova M.A. Effect of valinomycin on respiration, changes of medium pH, and volume in mitochondria from mung bean hypocotyls. Russian plant physiology, 1993, vol. 40, no. 3, pp. 375-380. Vyssokikh M.Y., Holtze S., Averina O.A., Lyamzaev K.G., Panteleeva A.A., Marey M.V., Zinovkin R.A., Severin F.F., Skulachev M.V., Fasel N., Hildebrandt T.B., Skulachev V.P. Mild depolarization of the inner mitochondrial membrane is a crucial component of an anti-aging program. Proc Natl Acad Sci USA., 2020, vol. 117, no. 12, pp. 6491-6501. DOI: 10.1073/pnas.1916414117. Vyssokikh M.Y., Holtze S., Averina O.A., Lyamzaev K.G., Panteleeva A.A., Marey M.V., Zinovkin R.A., Severin F.F., Skulachev M.V., Fasel N., Hildebrandt T.B., Skulachev V.P. Mild depolarization of the inner mitochondrial membrane is a crucial component of an anti-aging program. Proc Natl Acad Sci USA., 2020, vol. 117, no. 12, pp. 6491-6501. DOI: 10.1073/pnas.1916414117. Dröse S., Brandt U. The mechanism of mitochondrial superoxide production by the cytochrome bc1 complex. Jю. Biol. Chem., 2008, vol. 283, no. 31, pp. 21649-54. DOI: 10.1074/jbc.M8032362001. Dröse S., Brandt U. The mechanism of mitochondrial superoxide production by the cytochrome bc1 complex. Jyu. Biol. Chem., 2008, vol. 283, no. 31, pp. 21649-54. DOI: 10.1074/jbc.M8032362001. Kasumov E.A., Kasumov R.E., Kasumova I.V. A mechano-chemiosmotic model for the coupling of electron and proton transfer to ATP synthesis in energy-transforming membranes: a personal perspective. Photosynth Res., 2015, vol. 123, no. 1, pp. 1-22. DOI: 10.1007/s11120-014-0043-3. Kasumov E.A., Kasumov R.E., Kasumova I.V. A mechano-chemiosmotic model for the coupling of electron and proton transfer to ATP synthesis in energy-transforming membranes: a personal perspective. Photosynth Res., 2015, vol. 123, no. 1, pp. 1-22. DOI: 10.1007/s11120-014-0043-3. Kasumov E.A., Kasumov R.E., Kasumova I.V. Mild depolarization of the inner mitochondrial membrane is a crucial component of the mechano-chemiosmotic mechanism of coupling. J. Nov. Physiother. Phys. Rehabil., 2020, vol. 7, no. 1, pp. 033-035. DOI: https://dx.doi.org/10.17352/2455-5487.000075. Kasumov E.A., Kasumov R.E., Kasumova I.V. Mild depolarization of the inner mitochondrial membrane is a crucial component of the mechano-chemiosmotic mechanism of coupling. J. Nov. Physiother. Phys. Rehabil., 2020, vol. 7, no. 1, pp. 033-035. DOI: https://dx.doi.org/10.17352/2455-5487.000075. Andrzejewski S., Gravel S-P., Pollak M., St-Pierre J. Metformin Directly Acts on Mitochondria to Alter Cellular Bioenergetics. Cancer Metab., 2014, vol. 2, no. 12. DOI: 10.1186/2049-3002-2-12. Andrzejewski S., Gravel S-P., Pollak M., St-Pierre J. Metformin Directly Acts on Mitochondria to Alter Cellular Bioenergetics. Cancer Metab., 2014, vol. 2, no. 12. DOI: 10.1186/2049-3002-2-12. Dehkordi A.H., Abbaszadeh A., Mir S., Hasanvand A. Metformin and its anti-inflammatory and anti-oxidative effects; new concepts. J. Renal. Inj. Prev., 2019, vol. 8, no.1, pp. 54-61. DOI: 10.15171/jrip.2019.11. Dehkordi A.H., Abbaszadeh A., Mir S., Hasanvand A. Metformin and its anti-inflammatory and anti-oxidative effects; new concepts. J. Renal. Inj. Prev., 2019, vol. 8, no.1, pp. 54-61. DOI: 10.15171/jrip.2019.11. Kolosova, N.G., Vitovtov, A.O., Stefanova, N.A. Metformin reduces the signs of sarcopenia in old OXYS rats. Adv. Gerontol., 2016, vol. 6, pp. 70-74. DOI: 10.1134/S2079057016010069. Kolosova, N.G., Vitovtov, A.O., Stefanova, N.A. Metformin reduces the signs of sarcopenia in old OXYS rats. Adv. Gerontol., 2016, vol. 6, pp. 70-74. DOI: 10.1134/S2079057016010069. Emelyanova L., Gudlawar S., Cosic M., Mirza M., Rizvi F., Holmuhamedov E., Downey F., Tajik A., Jahangir A. Metformin Inhibits Mitochondrial Permeability Transition Pore Opening in Human Cardiac Mitochondria. Circulation Research., 2014, vol. 115, p. A322. Emelyanova L., Gudlawar S., Cosic M., Mirza M., Rizvi F., Holmuhamedov E., Downey F., Tajik A., Jahangir A. Metformin Inhibits Mitochondrial Permeability Transition Pore Opening in Human Cardiac Mitochondria. Circulation Research., 2014, vol. 115, p. A322. Kasumov E.A., Kasumov R.E., Kasumova I.V. On the MechanoChemiosmotic Mechanism of Action of Guanidinies on Functional Activity of Mitochondria and Aging. Organic Chem. Curr. Res., 2015, vol. 4, pp. 1-7. DOI: 10.4172/2161-0401.1000136. Kasumov E.A., Kasumov R.E., Kasumova I.V. On the MechanoChemiosmotic Mechanism of Action of Guanidinies on Functional Activity of Mitochondria and Aging. Organic Chem. Curr. Res., 2015, vol. 4, pp. 1-7. DOI: 10.4172/2161-0401.1000136. Касумов Э.А., Касумов Р.Э., Касумова И.В. Механизм трансформации энергии согласно механо-хемиосмотической модели. Актуальные вопросы биологической физики и химии. БФФХ-2019: матер. XIV междунар. науч. конф., 21-24 ноября г. Москва, 2019, с. 94. @@[Kasumov E.A., Kasumov R.E., Kasumova I.V. Mechanism of energy transformation according to the mechano-chemiosmotic model. Modern Trends in Biological Physics and Chemistry. BPPC-2019: proceedings of XIV International Scientific Conference, Moscow, 2019, p. 94.] Kasumov E.A., Kasumov R.E., Kasumova I.V. Mehanizm transformacii energii soglasno mehano-hemiosmoticheskoy modeli. Aktual'nye voprosy biologicheskoy fiziki i himii. BFFH-2019: mater. XIV mezhdunar. nauch. konf., 21-24 noyabrya g. Moskva, 2019, s. 94. @@[Kasumov E.A., Kasumov R.E., Kasumova I.V. Mechanism of energy transformation according to the mechano-chemiosmotic model. Modern Trends in Biological Physics and Chemistry. BPPC-2019: proceedings of XIV International Scientific Conference, Moscow, 2019, p. 94.] Singh N.B., Shiva Saran Das, Singh A.K. Physical Chemistry: Volume II. New Age International Pvt Ltd Publishers, 2009, 579 p. Singh N.B., Shiva Saran Das, Singh A.K. Physical Chemistry: Volume II. New Age International Pvt Ltd Publishers, 2009, 579 p. Kodera, N., Ando, T. The path to visualization of walking myosin V by high-speed atomic force microscopy. Biophys. Rev., 2014, vol. 6. no. 3-4, pp. 237-260. Kodera, N., Ando, T. The path to visualization of walking myosin V by high-speed atomic force microscopy. Biophys. Rev., 2014, vol. 6. no. 3-4, pp. 237-260. Tominaga Y., Shimmen T., Tazawa M. Control of cytoplasmic streaming by extracellular Ca2+ in permeabilized Nitella cells. Protoplasma, 1983, vol. 116, pp. 75-77. Tominaga Y., Shimmen T., Tazawa M. Control of cytoplasmic streaming by extracellular Ca2+ in permeabilized Nitella cells. Protoplasma, 1983, vol. 116, pp. 75-77. Жерелова О.М., Катаев А.А., Грищенко В.М., Штанчаев Р.Ш. Галоперидол-модулятор ионного транспорта клеток Chara Corallina. Цитология, 2016, т. 58, № 8, c. 646-654. @@[Zherelova O.M., Kataev A.A., Grischenko V.M., Shtanchaev R.S. Haloperidol modulates ionic transport of chara coralline cells. Tsitologia, 2016, vol. 58, no. 8, pp. 646-654. (In Russ.)] Zherelova O.M., Kataev A.A., Grischenko V.M., Shtanchaev R.Sh. Galoperidol-modulyator ionnogo transporta kletok Chara Corallina. Citologiya, 2016, t. 58, № 8, c. 646-654. @@[Zherelova O.M., Kataev A.A., Grischenko V.M., Shtanchaev R.S. Haloperidol modulates ionic transport of chara coralline cells. Tsitologia, 2016, vol. 58, no. 8, pp. 646-654. (In Russ.)] Bridges H.R., Jones A.J., Pollak M.N., Hirst J. Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochem J., 2014, vol. 462, no. 3, pp. 475-487. DOI: 10.1042/BJ20140620. Bridges H.R., Jones A.J., Pollak M.N., Hirst J. Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochem J., 2014, vol. 462, no. 3, pp. 475-487. DOI: 10.1042/BJ20140620. Papa S., Tuena de Gómez-Puyou M., Gómez-Puyou A. On the mechanism of action of alkyl-guanidines on oxidative phosphorylation in mitochondria. Eur J Biochem., 1975, vol. 55, no. 1, pp. 1-8. Papa S., Tuena de Gómez-Puyou M., Gómez-Puyou A. On the mechanism of action of alkyl-guanidines on oxidative phosphorylation in mitochondria. Eur J Biochem., 1975, vol. 55, no. 1, pp. 1-8. Heffernan K.S., Fahs C.A., Ranadive S.M., Patvardhan E.A. L-arginine as a nutritional prophylaxis against vascular endothelial dysfunction with aging. J Cardiovasc Pharmacol Ther., 2010, vol. 15, no. 1, pp. 17-23. DOI: 10.1177/1074248409354599. Heffernan K.S., Fahs C.A., Ranadive S.M., Patvardhan E.A. L-arginine as a nutritional prophylaxis against vascular endothelial dysfunction with aging. J Cardiovasc Pharmacol Ther., 2010, vol. 15, no. 1, pp. 17-23. DOI: 10.1177/1074248409354599. Mitchell T.R., Glenfield K., Jeyanthan K., Zhu X.D. Arginine methylation regulates telomere length and stability. Mol Cell Biol., 2009, vol. 29, no. 18, pp. 4918-4934. DOI: 10.1128/MCB.00009-09P. Mitchell T.R., Glenfield K., Jeyanthan K., Zhu X.D. Arginine methylation regulates telomere length and stability. Mol Cell Biol., 2009, vol. 29, no. 18, pp. 4918-4934. DOI: 10.1128/MCB.00009-09P. Böger R.H., Bode-Böger S.M., The clinical pharmacology of L-arginine. Annu. Rev. Pharmacol. Toxicol., 2001, vol. 41, pp. 79-99. DOI: 10.1146/annurev.pharmtox.41.1.79. Böger R.H., Bode-Böger S.M., The clinical pharmacology of L-arginine. Annu. Rev. Pharmacol. Toxicol., 2001, vol. 41, pp. 79-99. DOI: 10.1146/annurev.pharmtox.41.1.79. Wu G., Morris S.M., Jr. Arginine metabolism: nitric oxide and beyond. Biochem. J., 1998, vol. 336, pp. 1-17. DOI: 10.1042/bj3360001. Wu G., Morris S.M., Jr. Arginine metabolism: nitric oxide and beyond. Biochem. J., 1998, vol. 336, pp. 1-17. DOI: 10.1042/bj3360001. Mailoo VJ, Rampes S. Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence. Integr. Med. (Encinitas), 2017, vol. 16, no.3, pp. 42-46. Mailoo VJ, Rampes S. Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence. Integr. Med. (Encinitas), 2017, vol. 16, no.3, pp. 42-46. Griffith R.S., Walsh D.E., Myrmel K.H., Thompson R.W., Behforooz A. Success of L-lysine Therapy in Frequently Recurrent Herpes Simplex Infection. Treatment and Prophylaxis. Dermatologica, 1987, vol. 175, no. 4, pp. 183-90. Griffith R.S., Walsh D.E., Myrmel K.H., Thompson R.W., Behforooz A. Success of L-lysine Therapy in Frequently Recurrent Herpes Simplex Infection. Treatment and Prophylaxis. Dermatologica, 1987, vol. 175, no. 4, pp. 183-90. Kobayashi N., Oka N., Mayumi M., Shimada K., Ishii A., Tatebayashi Y., Shigeta M., Yanagisawa H., Kondo K. Human Herpesvirus 6B Greatly Increases Risk of Depression by Activating Hypothalamic-Pituitary - Adrenal Axis during Latent Phase of Infection. iScience, 2020, vol. 23, no. 6. DOI: 10.1016/j.isci.2020.101187. Kobayashi N., Oka N., Mayumi M., Shimada K., Ishii A., Tatebayashi Y., Shigeta M., Yanagisawa H., Kondo K. Human Herpesvirus 6B Greatly Increases Risk of Depression by Activating Hypothalamic-Pituitary - Adrenal Axis during Latent Phase of Infection. iScience, 2020, vol. 23, no. 6. DOI: 10.1016/j.isci.2020.101187. Itzhaki R.F. Corroboration of a Major Role for Herpes Simplex Virus Type 1 in Alzheimer’s Disease. Frontiers in Aging Neuroscience, 2018, vol. 10, no. 324. DOI: 10.3389/fnagi.2018.00324. Itzhaki R.F. Corroboration of a Major Role for Herpes Simplex Virus Type 1 in Alzheimer’s Disease. Frontiers in Aging Neuroscience, 2018, vol. 10, no. 324. DOI: 10.3389/fnagi.2018.00324. Kondadi A.K., Anand R., Hansch S., Urbach J., Zobel T., Wolf D.M., Segawa M., Liesa M., Shirihai O.S., Weidtkamp-Peters S., Reichert A.S. Cristae undergo continuous cycles of membrane remodelling in a MICOS-dependent manner. EMBO Rep., 2020, vol. 21, p. e49776. DOI: 10.15252/embr.201949776. Kondadi A.K., Anand R., Hansch S., Urbach J., Zobel T., Wolf D.M., Segawa M., Liesa M., Shirihai O.S., Weidtkamp-Peters S., Reichert A.S. Cristae undergo continuous cycles of membrane remodelling in a MICOS-dependent manner. EMBO Rep., 2020, vol. 21, p. e49776. DOI: 10.15252/embr.201949776.