Metabolic regulation in mitochondria as a prospective way of body rejuvenation

Literature review

Authors

DOI:

https://doi.org/10.18370/2309-4117.2021.59.78-82

Keywords:

mitochondrial dysfunction, aging, body rejuvenation, xylitol, Xylate

Abstract

Scientists around the world are looking for ways to achieve high-quality and active longevity. The complexity of these searches is associated with the lack of unified concept of aging mechanisms, the problem of extrapolating the results of studies of geroprotectors from model organisms to humans. Therefore, modern medicine can only slow down the aging process so far. Nevertheless, it has been proven that disturbances in the functioning of mitochondria are an important link in the pathogenesis of aging; therefore, regulation of their metabolism is a promising way of rejuvenating the body. A decrease in protein synthesis and a general decrease in the intensity of the oxidative enzymes action are interrelated. Energy production for the protein and DNA synthesis decreases with a decrease in the intensity of oxidative processes. Dysfunction of mitochondrial adaptive reactions also develops with age, which may be associated with the low efficiency of the NADH dehydrogenase complex – NADH ubiquinone oxidoreductase, which catalyzes the transfer of electrons from NADH to ubiquinone/coenzyme Q10, resulting in a decrease in electron transport and an increase of active oxygen forms. Coenzyme Q10 reducing plays a very important role in the aging process, as it is an antioxidant and, unlike other antioxidants, is produced in the body. An increase in mitochondrial biogenesis, as well as an increase in the rate and efficiency of mitochondrial metabolism (with a calorie restricted diet for example) helps to improve the energy supply of cells and prolong life.
A drug based on xylitol Xylate can be a source of triglycerophosphate by metabolism through the pentose phosphate cycle and thereby reduce the amount of free fatty acids that can be oxidized into acetyl-CoA, increases the content of adenosine triphosphate acid and other adenine nucleotides in liver, and has a pronounced antiketogenic effect. It can reduce intoxication and improve microcirculation, which is especially important for high-quality and active longevity.
Activation of mitochondrial metabolism is a promising direction in the aging prevention, since it allows balancing metabolic processes not only in cells, but also in body as a whole.

Author Biographies

E.G. Manzhalii, O.O. Bogomolets National Medical University; Ukrainian Liver Foundation; Global Longevity Institute; Clinic Verum Expert, Kyiv

Associate professor, Department of Propedeutics of Internal Medicine;

President;

CEO;

Chief of Hepatology department

V.V. Dunaevskaya, National Cancer Institute; SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”, Kyiv

PhD, gynecologist-oncologist;

Senior researcher, Endocrine Gynecology Department

O.M. Baka, SSI «CIMT of the NAS of Ukraine», Kyiv

Researcher, Department of Diagnostics and Treatment of Metabolic Diseases, head of the Gastroenterology Department

References

  1. Alfarouk, K.O., Verduzco, D., Rauch, C., et al. “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question.” Oncoscience 1.12 (2014).
  2. Arai, Y., Hirose, N., Kawamura, M., et al. “Lipid and lipoprotein profile of Japanese centenarians–high prevalence of hypo beta lipoproteinemia.” Nihon Ronen Igakkai Zasshi 34 (1997): 202–8.
  3. Bar-Or, D., Carrick, M., Tanner, A., et al. “Overcoming the Warburg Effect: Is It the Key to Survival in Sepsis?” Journal of Critical Care (2018).
  4. Brunet, A., Berger, S.L. “Epigenetics of Aging and Aging-related Disease.” The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 69 Suppl 1 (2014): S17–S20.
  5. Berhane, F., Fite, A., Daboul, N., et al. “Plasma Lactate Levels Increase during Hyperinsulinemic Euglycemic Clamp and Oral Glucose Tolerance Test.” Journal of Diabetes Research (2015).
  6. Bar-Or, D., Rael, L.T., Madayag, R.M., et al. “Stress Hyperglycemia in Critically Ill Patients: Insight Into Possible Molecular Pathways.” Frontiers in Medicine: Intensive Care Medicine & Anesthesiology (2019).
  7. Boccardi, V., Paolisso, G. “Telomerase activation: A potential key modulator for human healthspan and longevity.” Ageing research reviews 15 (2014): 1–5.
  8. Chen, Z., Liu, M., Li, L., Chen, L. “Involvement of the Warburg Effect in Non-tumor Diseases Processes.” Journal of Cell Physiology 233.4 (2018).
  9. Dudinskaya, E.N., Tkacheva, O.N. “Hypoglycemia: Managing Diabetes Risk.” Endokrinologiya: novosti, mneniya, obuchenie 1 (2013): 89–98
  10. Chernyaeva, I., Mykytyuk, M., Karachentsev, Y., Kravchun, N. “Level of urikemia in patients with diabetes mellitus and anthropometric indices; Clinical and biochemical correlations.” Problemi Endokrinnoi Patologii 2 (2019): 73–80.
  11. Garfin, P.M., Min, D., Bryson, J.L., et al. “Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression.” The Journal of experimental medicine 210.6 (2013): 1087–97.
  12. Gormeli, K.N., Orak, M., Ustundag, M. “Relation between Stress Hyperglycemia and Mortality in Patients with Acute Myocardial Infarction. Eurasian Journal of Medicine & Oncology 2.3 (2018): 138–41.
  13. Gunkov, S., Tatarchuk, T.F., Zhminko, P.A., Regeda, S. “Effect of manganese and nickel on prolactin levels in women with polycystic ovary syndrome.” Georgian medical news 289 (2019): 21–5.
  14. Gesing, A., Al-Regaiey, K.A., Bartke, A., Masternak, M.M. “Growth Hormone Abolishes Beneficial Effects of Calorie Restriction in Long-Lived Ames Dwarf Mice.” Experimental gerontology 58 (2014): 219–29.
  15. Hiebert, P.R., Boivin, W.A., Abraham, T., et al. “Granzyme B contributes to extracellular matrix remodeling and skin aging in apolipoprotein E knockout mice.” Experimental gerontology 46.6 (2011): 489–99.
  16. Hill, S., Van Remmen, H. “Mitochondrial stress signaling in longevity: A new role for mitochondrial function in aging.” Redox Biology 2 (2014): 936–44.
  17. Islam, M.S. “Effects of Xylitol as a Sugar Substitute on Diabetes-related Parameters in Nondiabetic Rats.” Journal of Medicinal Food 14.5 (2011): 505–11.
  18. Fujikawa, T., Berglund, E.D., Patel, V.R., et al. “Leptin engages a hypothalamic neurocircuitry to permit survival in the absence of insulin.” Cell Metab 18.3 (2013).
  19. Joris Deelen, et al. “Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age.” Hum Mol Genet 23.16 (2014): 4420–32.
  20. Jing Ye, et al. “Transcriptional outcome of telomere signaling.” Nature Reviews Genetics 15 (2014): 491–503.
  21. Kim, J.W., Dang, C.V. “Cancer's molecular sweet tooth and the Warburg effect.” Cancer Res 66.18 (2006).
  22. Kopchick, J.J., List, E.O., Kelder, B., et al. “Evaluation of growth hormone (GH) action in mice: Discovery of GH receptor antagonists and clinical indications.” Molecular and cellular endocrinology 386.1 (2014): 34–45.
  23. Manzhalii, E.G. “Metabolic regulation in mitochondria as a promising path rejuvenation of the body.” Medical Aspects of Women's Health 3.138 (2021).
  24. El Mesallamy, H.O., Hamdy, N.M., Mostafa, D.M., Amin, A.I. “The Serine Protease Granzyme B as an Inflammatory Marker, in Relation to the Insulin Receptor Cleavage in Human Obesity and Type 2 Diabetes Mellitus.” Journal of Interferon & Cytokine Research 34.3 (2014): 179–86.
  25. Long, Y.C., Tan, T.M., Takao, I., Tang, B.L. “The biochemistry and cell biology of aging: metabolic regulation through mitochondrial signaling.” American Journal of Physiology-Endocrinology and Metabolism 306.6 (2014): E581–E591.
  26. Madonna, R., Taylor, D.A., Geng, Y.J., et al. “Transplantation of mesenchymal cells rejuvenated by the overexpression of telomerase and myocardin promotes revascularization and tissue repair in a murine model of hindlimb ischemia.” Circulation research 113.7 (2013): 902–14.
  27. Mitchell, T.R., Zhu, X.D. “Methylated TRF2 associates with the nuclear matrix and serves as a potential biomarker for cellular senescence.” Aging (Albany NY) 6.4 (2014): 248–63.
  28. Motswaledi, M.S., Kasvosve, I., Oguntibeju, O.O. “The Role of Red Blood Cells in Enhancing or Preventing HIV Infection and Other Diseases.” BioMed Research International (2013).
  29. Nelson Chau. “Let-7 Coordinately Suppresses Components of the Amino Acid Sensing Pathway to Repress mTORC1 and Induce Autophagy.” Cell Metabolism 20.4 (2014): 626.
  30. Packer, M. “Activation and inhibition of sodium-hydrogen exchanger is a mechanism that links the pathophysiology and treatment of diabetes mellitus with that of heart failure.” Circulation 136.16 (2017).
  31. Potter, M., Newport, E., Morten, K.J. “The Warburg Effect: 80 Yeats on.” Biochemical Society Transactions 44 (2016): 1499–505.
  32. Ruan, Q., Qian, F., Yu, Z. “Effects of polymorphisms in immunity-related genes on the immune system and successful aging.” Current opinion in immunology 29 (2014): 49–55.
  33. Regmi, S.G., Rolland, S.G., Conradt, B. “Age-dependent changes in mitochondrial morphology and volume are not predictors of lifespan.” Aging (Albany NY) 6.2 (2014): 118–30.
  34. Galic, S., Sachithanandan, N., Kay, T.W., Steinberg, G.R. “Suppressor of cytokine signalling (SOCS) proteins as guardians of inflammatory responses critical for regulating insulin sensitivity.” Biochemical Journal 461.2 (2014): 177–88.
  35. Steinthorsdottir, V., Thorleifsson, G., Sulem, P., et al. “Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes.” Nature genetics 46.3 (2014): 294–8.
  36. Sanders, J.L., Minster, R.L., Barmada, M.M., et al. “Heritability of and mortality prediction with a longevity phenotype: The Healthy Aging Index.” The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 69.4 (2014): 479–85.
  37. Tan, Q., Soerensen, M., Kruse, T.A., et al. “A novel permutation test for case-only analysis identifies epistatic effects on human longevity in the FOXO gene family.” Aging Cell 12 (2013): 690–4.
  38. Tedone, E., Arosio, B., Gussago, C., et al. “Leukocyte telomere length and prevalence of age-related diseases in semisupercentenarians, centenarians and centenarians' offspring.” Experimental gerontology 58 (2014): 90–5.
  39. Wijsman, C.A., Rozing, M.P., Streefland, T.C., et al. “Familial longevity is marked by enhanced insulin sensitivity.” Aging Cell 10.1 (2011): 114–21.
  40. Zhang, Z., Burnley, P., Coder, B., Su, D.M. “Insights on FoxN1 biological significance and usages of the "nude" mouse in studies of T-lymphopoiesis.” Int J Biol Sci 8.8 (2012): 1156–67.
  41. Zook, E.C., Krishack, P.A., Zhang, S., et al. “Overexpression of Foxn1 attenuates age-associated thymic involution and prevents the expansion of peripheral CD4 memory T cells.” Blood 118.22 (2011): 5723–31.

Published

2021-07-22

How to Cite

Manzhalii, E., Dunaevskaya, V., & Baka, O. (2021). Metabolic regulation in mitochondria as a prospective way of body rejuvenation: Literature review. REPRODUCTIVE ENDOCRINOLOGY, (59), 78–82. https://doi.org/10.18370/2309-4117.2021.59.78-82

Issue

Section

Gynecology