ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet12934ometendo-12934Research ArticleОБЗОРЫREVIEWSРоль ИФР-1/СТГ в процессах старения и развитии возраст-ассоциированных заболеванийThe role of IGF-1/GH in the aging process and the development of age-related diseaseshttps://orcid.org/0000-0002-3544-5347ИльющенкоА. К.IlyushchenkoA. K.

Ильющенко Анна Константиновна 

129226, Москва, ул. 1-я Леонова, д. 16

Anna K. Ilyushchenko

129226, 16 Leonova 1st street, Moscow

anna.savicheva1998@yandex.ruhttps://orcid.org/0000-0002-2028-3939МачехинаЛ. В.MachekhinaL. V.

Мачехина Любовь Викторовна, к.м.н.

Москва

Liubov V. Machekhina, MD, PhD

Moscow

mlv66@list.ruhttps://orcid.org/0000-0002-3657-0676СтражескоИ. Д.StrazheskoI. D.

Стражеско Ирина Дмитриевна, д.м.н., профессор 

Москва

Irina D. Strazhesko, MD, PhD, professor

Moscow

strazhesko_id@rgnkc.ruhttps://orcid.org/0000-0002-4193-688XТкачеваО. Н.TkachevaO. N.

Ткачева Ольга Николаевна, д.м.н., профессор 

Москва

Olga N. Tkacheva, MD, PhD, professor

Moscow

tkacheva@rgnkc.ruРоссийский Геронтологический научно-клинический центрРоссияRussian Gerontology Research and Clinical CentreRussian Federation202306062023202149157Copyright © Ильющенко А.К., Мачехина Л.В., Стражеско И.Д., Ткачева О.Н., 20232023Ильющенко А.К., Мачехина Л.В., Стражеско И.Д., Ткачева О.Н.Ilyushchenko A.K., Machekhina L.V., Strazhesko I.D., Tkacheva O.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/12934

Одно из важнейших направлений в современной геронауке — поиск биомеханизмов старения и геропротективных методов. В последние годы все большее внимание стало уделяться роли возраст-индуцированного снижения уровня инсулиноподобного фактора роста 1 (ИФР-1), изменениям в регуляторном механизме влияния оси соматотропного гормона (СТГ)/ИФР-1 на гормонально-метаболический профиль; процессам, которые запускаются со снижением активности оси СТГ/ИФР-1. Уровни ИФР-1 по-разному коррелируют со многими возраст-ассоциированными заболеваниями: сахарным диабетом, онкологическими заболеваниями, сердечно-сосудистыми заболеваниями. Снижение уровня ИФР-1 и гормона роста в пожилом возрасте может как способствовать ухудшению течения ряда патологий, так и обладать протективным эффектом в возникновении отдельных нозологий. Возможность замедления старения с помощью ИФР-1 в фундаментальных исследованиях привела к проведению исследований, направленных на изучение возможности применения в клинической практике препаратов ИФР-1 и гормона роста с целью замедления старения. Нами были изучена литература на платформах Pubmed, Scopus за последние 10 лет с целью поиска информации об основных механизмах влияния ИФР-1 на процесс старения, о связи между уровнями ИФР-1 и основными возраст-ассоциированными заболеваниями. Был проведен отбор научных публикаций, посвященных изучению роли ИФР-1 в старении, развитии возраст-ассоциированных заболеваний. Поиск осуществлялся с использованием ключевых слов ИФР-1, СТГ, заместительная гормональная терапия, в обзор были включены данные более 60 научных публикаций.

One of the most important trends in geroscience is the search for the biomechanisms of aging and geroprotective methods. In recent years, more and more attention has been paid to the role of age-related decline in IGF-1 levels; processes that start with a decrease in the activity of the GH/IGF-1 axis. IGF-1 levels correlate differently with many age-associated diseases: diabetes mellitus, cancer, cardiovascular disease. A decrease in the level of IGF-1 and growth hormone in the elderly can contribute to the deterioration of the course of some pathologies, and also have a protective effect in the occurrence of different nosologies. The possibility of slowing down aging with the help of IGF-1 in basic research led to research aimed at studying the possibility of using IGF-1 preparations and growth hormone in clinical practice to slow down aging. We have studied the literature on the Pubmed platform, Scopus for the past 10 years in order to find some new information regarding influence of IGF-1 on aging, about the association between IGF-1 levels and major age-related diseases. We analyzed data of publications on the role of IGF-1 in aging and the development of age-related diseases. The search was carried out using key words: IGF-1, growth hormone, aging, the review included data from more than 60 publications.

старениеИФР-1соматотропный гормонгормональная терапияagingIGF-1growth hormonehormone therapyReferencesBartke A. Growth hormone and aging: Updated review. World J Mens Health. 2019;37(1):19-30. doi: https://doi.org/10.5534/wjmh.180018Bartke A. Growth hormone and aging: Updated review. World J Mens Health. 2019;37(1):19-30. doi: https://doi.org/10.5534/wjmh.180018Bidlingmaier M, Friedrich N, Emeny RT, et al. Reference intervals for insulin-like growth factor-1 (igf-i) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations [published correction appears in J Clin Endocrinol Metab. 2020;105(12)]. J Clin Endocrinol Metab. 2014;99(5):1712-1721. doi: https://doi.org/10.1210/jc.2013-3059Bidlingmaier M, Friedrich N, Emeny RT, et al. Reference intervals for insulin-like growth factor-1 (igf-i) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations [published correction appears in J Clin Endocrinol Metab. 2020;105(12)]. J Clin Endocrinol Metab. 2014;99(5):1712-1721. doi: https://doi.org/10.1210/jc.2013-3059Stojanovic M, Popevic M, Pekic S, et al. Serum Insulin-Like Growth Factor-1 (IGF-1) age-specific reference values for healthy adult population of Serbia. Acta Endocrinol (Buchar). 2021;17(4):462-471. doi: https://doi.org/10.4183/aeb.2021.462Stojanovic M, Popevic M, Pekic S, et al. Serum Insulin-Like Growth Factor-1 (IGF-1) age-specific reference values for healthy adult population of Serbia. Acta Endocrinol (Buchar). 2021;17(4):462-471. doi: https://doi.org/10.4183/aeb.2021.462Zhang WB, Ye K, Barzilai N, Milman S. The antagonistic pleiotropy of insulin-like growth factor 1. Aging Cell. 2021;20(9):e13443. doi: https://doi.org/10.1111/acel.13443Zhang WB, Ye K, Barzilai N, Milman S. The antagonistic pleiotropy of insulin-like growth factor 1. Aging Cell. 2021;20(9):e13443. doi: https://doi.org/10.1111/acel.13443Rahmani J, Montesanto A, Giovannucci E, et al. Association between IGF-1 levels ranges and all-cause mortality: A meta-analysis. Aging Cell. 2022;21(2):e13540. doi: https://doi.org/10.1111/acel.13540Rahmani J, Montesanto A, Giovannucci E, et al. Association between IGF-1 levels ranges and all-cause mortality: A meta-analysis. Aging Cell. 2022;21(2):e13540. doi: https://doi.org/10.1111/acel.13540Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D. The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study. J Clin Endocrinol Metab. 2004;89(1):114-120. doi: https://doi.org/10.1210/jc.2003-030967Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D. The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study. J Clin Endocrinol Metab. 2004;89(1):114-120. doi: https://doi.org/10.1210/jc.2003-030967Kenyon C, Chang J, Gensch E, et al. A C. elegans mutant that lives twice as long as wild type. Nature. 1993;366(6454):461-464. doi: https://doi.org/10.1038/366461a0Kenyon C, Chang J, Gensch E, et al. A C. elegans mutant that lives twice as long as wild type. Nature. 1993;366(6454):461-464. doi: https://doi.org/10.1038/366461a0Broughton SJ, Piper MD, Ikeya T, et al. Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci U S A. 2005;102(8):3105-3110. doi: https://doi.org/10.1073/pnas.0405775102Broughton SJ, Piper MD, Ikeya T, et al. Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci U S A. 2005;102(8):3105-3110. doi: https://doi.org/10.1073/pnas.0405775102Brown-Borg HM, Borg KE, Meliska CJ, Bartke A. Dwarf mice and the ageing process. Nature. 1996;384(6604):33. doi: https://doi.org/10.1038/384033a0Brown-Borg HM, Borg KE, Meliska CJ, Bartke A. Dwarf mice and the ageing process. Nature. 1996;384(6604):33. doi: https://doi.org/10.1038/384033a0Tatar M, Kopelman A, Epstein D, et al. A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science. 2001;292(5514):107-110. doi: https://doi.org/10.1126/science.1057987Tatar M, Kopelman A, Epstein D, et al. A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science. 2001;292(5514):107-110. doi: https://doi.org/10.1126/science.1057987Bonkowski MS, Rocha JS, Masternak MM, et al. Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction. Proc Natl Acad Sci. 2006;103(20):7901-7905. doi: https://doi.org/10.1073/pnas.0600161103Bonkowski MS, Rocha JS, Masternak MM, et al. Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction. Proc Natl Acad Sci. 2006;103(20):7901-7905. doi: https://doi.org/10.1073/pnas.0600161103Liu J-P, Baker J, Perkins AS, et al. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell. 1993;75(1):59-72. doi: https://doi.org/10.1016/S0092-8674(05)80084-4Liu J-P, Baker J, Perkins AS, et al. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell. 1993;75(1):59-72. doi: https://doi.org/10.1016/S0092-8674(05)80084-4Holzenberger M. The GH/IGF-I axis and longevity. Eur J Endocrinol. 2004;151(S1):S23-27 doi: https://doi.org/10.1530/eje.0.151s023Holzenberger M. The GH/IGF-I axis and longevity. Eur J Endocrinol. 2004;151(S1):S23-27 doi: https://doi.org/10.1530/eje.0.151s023Thomas M, Berni E, Jenkins-Jones S, et al. Insulin-like growth factor-1, growth hormone and disease outcomes in acromegaly: A population study. Clin Endocrinol (Oxf ). 2021;95(1):143-152. doi: https://doi.org/10.1111/cen.14468Thomas M, Berni E, Jenkins-Jones S, et al. Insulin-like growth factor-1, growth hormone and disease outcomes in acromegaly: A population study. Clin Endocrinol (Oxf ). 2021;95(1):143-152. doi: https://doi.org/10.1111/cen.14468Laron Z. Lessons from 50 years of study of laron syndrome. Endocr Pract. 2015;21(12):1395-1402. doi: https://doi.org/10.4158/EP15939.RALaron Z. Lessons from 50 years of study of laron syndrome. Endocr Pract. 2015;21(12):1395-1402. doi: https://doi.org/10.4158/EP15939.RAOlleros Santos-Ruiz M, Sádaba MC, Martín-Estal I, et al. The single IGF-1 partial deficiency is responsible for mitochondrial dysfunction and is restored by IGF-1 replacement therapy. Growth Horm IGF Res. 2017;35(1):21-32. doi: https://doi.org/10.1016/j.ghir.2017.05.007Olleros Santos-Ruiz M, Sádaba MC, Martín-Estal I, et al. The single IGF-1 partial deficiency is responsible for mitochondrial dysfunction and is restored by IGF-1 replacement therapy. Growth Horm IGF Res. 2017;35(1):21-32. doi: https://doi.org/10.1016/j.ghir.2017.05.007Sádaba MC, Martín-Estal I, Puche JE, Castilla-Cortázar I. Insulinlike growth factor 1 (IGF-1) therapy: Mitochondrial dysfunction and diseases. Biochim Biophys Acta. 2016;1862(7):1267-1278. doi: https://doi.org/10.1016/j.bbadis.2016.03.010Sádaba MC, Martín-Estal I, Puche JE, Castilla-Cortázar I. Insulinlike growth factor 1 (IGF-1) therapy: Mitochondrial dysfunction and diseases. Biochim Biophys Acta. 2016;1862(7):1267-1278. doi: https://doi.org/10.1016/j.bbadis.2016.03.010Morales-Garza LA, Puche JE, Aguirre GA, et al. Experimental approach to IGF-1 therapy in CCl4 -induced acute liver damage in healthy controls and mice with partial IGF-1 deficiency. J Transl Med. 2017;15(1):96. doi: https://doi.org/10.1186/s12967-017-1198-4Morales-Garza LA, Puche JE, Aguirre GA, et al. Experimental approach to IGF-1 therapy in CCl4 -induced acute liver damage in healthy controls and mice with partial IGF-1 deficiency. J Transl Med. 2017;15(1):96. doi: https://doi.org/10.1186/s12967-017-1198-4Martín AI, Priego T, Moreno-Ruperez Á, et al. IGF-1 and IGFBP-3 in Inflammatory Cachexia. Int J Mol Sci. 2021;22(17):9469. doi: https://doi.org/10.3390/ijms22179469Martín AI, Priego T, Moreno-Ruperez Á, et al. IGF-1 and IGFBP-3 in Inflammatory Cachexia. Int J Mol Sci. 2021;22(17):9469. doi: https://doi.org/10.3390/ijms22179469Геннадиник А.Г., Нелаева А.А. Роль инсулиноподобного фактора роста-I в метаболизме, регуляции клеточного обновления и процессах старения // Ожирение и метаболизм. — 2010. — Т. 7. — №2. — С. 10-15.Gennadinik AG, Nelaeva AA. Rol` insulinopodobnogo faktora rosta-I v metabolizme, regulyacii kletochnogo obnovleniya i processax stareniya. Obesity and metabolism. 2010;7(2);10-15. (In Russ.)].Ameline B, Kovac M, Nathrath M, et al. Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target? J Pathol Clin Res. 2021;7(2):165-172. doi: https://doi.org/10.1002/cjp2.191Ameline B, Kovac M, Nathrath M, et al. Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target? J Pathol Clin Res. 2021;7(2):165-172. doi: https://doi.org/10.1002/cjp2.191Alsina-Sanchis E, Figueras A, Lahiguera Á, et al. The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels. Int J Cancer. 2016;139(8):1894-1903. doi: https://doi.org/10.1002/ijc.30233Alsina-Sanchis E, Figueras A, Lahiguera Á, et al. The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels. Int J Cancer. 2016;139(8):1894-1903. doi: https://doi.org/10.1002/ijc.30233Lovly CM, McDonald NT, Chen H, et al. Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer. Nat Med. 2014;20(9):1027-1034. doi: https://doi.org/10.1038/nm.3667Lovly CM, McDonald NT, Chen H, et al. Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer. Nat Med. 2014;20(9):1027-1034. doi: https://doi.org/10.1038/nm.3667King H, Aleksic T, Haluska P, Macaulay VM. Can we unlock the potential of IGF-1R inhibition in cancer therapy? Cancer Treat Rev. 2014;40(9):1096-1105. doi: https://doi.org/10.1016/j.ctrv.2014.07.004King H, Aleksic T, Haluska P, Macaulay VM. Can we unlock the potential of IGF-1R inhibition in cancer therapy? Cancer Treat Rev. 2014;40(9):1096-1105. doi: https://doi.org/10.1016/j.ctrv.2014.07.004Janssen JA, Varewijck AJ. IGF-IR targeted therapy: past, present and future. Front Endocrinol (Lausanne). 2014;(5):224. doi: https://doi.org/10.3389/fendo.2014.00224Janssen JA, Varewijck AJ. IGF-IR targeted therapy: past, present and future. Front Endocrinol (Lausanne). 2014;(5):224. doi: https://doi.org/10.3389/fendo.2014.00224Vlahovic G, Meadows KL, Hatch AJ, et al. A Phase I Trial of the IGF-1R Antibody Ganitumab (AMG 479) in Combination with Everolimus (RAD001) and Panitumumab in Patients with Advanced Cancer. Oncologist. 2018;23(7):782-790. doi: https://doi.org/10.1634/theoncologist.2016-0377Vlahovic G, Meadows KL, Hatch AJ, et al. A Phase I Trial of the IGF-1R Antibody Ganitumab (AMG 479) in Combination with Everolimus (RAD001) and Panitumumab in Patients with Advanced Cancer. Oncologist. 2018;23(7):782-790. doi: https://doi.org/10.1634/theoncologist.2016-0377Ameline B, Kovac M, Nathrath M, et al. Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target? J Pathol Clin Res. 2021;7(2):165-172. doi: https://doi.org/10.1002/cjp2.191Ameline B, Kovac M, Nathrath M, et al. Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target? J Pathol Clin Res. 2021;7(2):165-172. doi: https://doi.org/10.1002/cjp2.191van Bunderen CC, Deijen JB, Drent ML. Effect of low-normal and high-normal IGF-1 levels on memory and wellbeing during growth hormone replacement therapy: a randomized clinical trial in adult growth hormone deficiency. Health Qual Life Outcomes. 2018;16(1):135. doi: https://doi.org/10.1186/s12955-018-0963-2van Bunderen CC, Deijen JB, Drent ML. Effect of low-normal and high-normal IGF-1 levels on memory and wellbeing during growth hormone replacement therapy: a randomized clinical trial in adult growth hormone deficiency. Health Qual Life Outcomes. 2018;16(1):135. doi: https://doi.org/10.1186/s12955-018-0963-2Olivares-Hernández JD, Balderas-Márquez JE, Carranza M, et al. Growth Hormone (GH) Enhances Endogenous Mechanisms of Neuroprotection and Neuroplasticity after Oxygen and Glucose Deprivation Injury (OGD) and Reoxygenation (OGD/R) in Chicken Hippocampal Cell Cultures. Neural Plast. 2021;2021:1-24. doi: https://doi.org/10.1155/2021/9990166Olivares-Hernández JD, Balderas-Márquez JE, Carranza M, et al. Growth Hormone (GH) Enhances Endogenous Mechanisms of Neuroprotection and Neuroplasticity after Oxygen and Glucose Deprivation Injury (OGD) and Reoxygenation (OGD/R) in Chicken Hippocampal Cell Cultures. Neural Plast. 2021;2021:1-24. doi: https://doi.org/10.1155/2021/9990166Sanchez-Bezanilla S, Åberg ND, Crock P, et al. Growth hormone treatment promotes remote hippocampal plasticity after experimental cortical stroke. Int J Mol Sci. 2020;21(12):4563. doi: https://doi.org/10.3390/ijms21124563Sanchez-Bezanilla S, Åberg ND, Crock P, et al. Growth hormone treatment promotes remote hippocampal plasticity after experimental cortical stroke. Int J Mol Sci. 2020;21(12):4563. doi: https://doi.org/10.3390/ijms21124563Angelini A, Bendini C, Neviani F, et al. Insulin-like growth factor-1 (IGF-1): relation with cognitive functioning and neuroimaging marker of brain damage in a sample of hypertensive elderly subjects. Arch Gerontol Geriatr. 2009;49(S1):5-12. doi: https://doi.org/10.1016/j.archger.2009.09.006Angelini A, Bendini C, Neviani F, et al. Insulin-like growth factor-1 (IGF-1): relation with cognitive functioning and neuroimaging marker of brain damage in a sample of hypertensive elderly subjects. Arch Gerontol Geriatr. 2009;49(S1):5-12. doi: https://doi.org/10.1016/j.archger.2009.09.006Wennberg AMV, Hagen CE, Machulda MM, et al. The association between peripheral total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 and functional and cognitive outcomes in the Mayo Clinic Study of Aging. Neurobiol Aging. 2018;(66):68-74. doi: https://doi.org/10.1016/j.neurobiolaging.2017.11.017Wennberg AMV, Hagen CE, Machulda MM, et al. The association between peripheral total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 and functional and cognitive outcomes in the Mayo Clinic Study of Aging. Neurobiol Aging. 2018;(66):68-74. doi: https://doi.org/10.1016/j.neurobiolaging.2017.11.017Federici M, Porzio O, Lauro D, et al. Increased abundance of insulin/insulin-like growth factor-i hybrid receptors in skeletal muscle of obese subjects is correlated with in vivo insulin sensitivity1. J Clin Endocrinol Metab. 1998;83(8):2911-2915. doi: https://doi.org/10.1210/jcem.83.8.4935Federici M, Porzio O, Lauro D, et al. Increased abundance of insulin/insulin-like growth factor-i hybrid receptors in skeletal muscle of obese subjects is correlated with in vivo insulin sensitivity1. J Clin Endocrinol Metab. 1998;83(8):2911-2915. doi: https://doi.org/10.1210/jcem.83.8.4935Paolisso G, Ammendola S, Del Buono A, et al. Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function. J Clin Endocrinol Metab. 1997;82(7):2204-2209. doi: https://doi.org/10.1210/jcem.82.7.4087Paolisso G, Ammendola S, Del Buono A, et al. Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function. J Clin Endocrinol Metab. 1997;82(7):2204-2209. doi: https://doi.org/10.1210/jcem.82.7.4087Belfiore A, Frasca F, Pandini G, et al. Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr Rev. 2009;30(6):586-623. doi: https://doi.org/10.1210/er.2008-0047Belfiore A, Frasca F, Pandini G, et al. Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr Rev. 2009;30(6):586-623. doi: https://doi.org/10.1210/er.2008-0047Giannoukakis N, Mi Z, Rudert WA, et al. Prevention of beta cell dysfunction and apoptosis activation in human islets by adenoviral gene transfer of the insulin-like growth factor I. Gene Ther. 2000;7(23):2015-2022. doi: https://doi.org/10.1038/sj.gt.3301333Giannoukakis N, Mi Z, Rudert WA, et al. Prevention of beta cell dysfunction and apoptosis activation in human islets by adenoviral gene transfer of the insulin-like growth factor I. Gene Ther. 2000;7(23):2015-2022. doi: https://doi.org/10.1038/sj.gt.3301333Пронин В.С., Колода Д.Е., Чаплыгина Е.В. Инсулиноподобные ростовые факторы в клинической практике: биологическая роль и перспективы использования // Клиницист. — 2008. — Т. 3. — №1 — С. 18-27.Pronin VS, Koloda DE, Chapligina EV. Clinical use of insulin-like growth factors: their biological action and perspectives of application. Klinicist. 2008;3(1);18-27. (In Russ.)].Burgos JI, Yeves AM, Barrena JP, et al. Nitric oxide and CaMKII: Critical steps in the cardiac contractile response To IGF-1 and swim training. J Mol Cell Cardiol. 2017;112(8):16-26. doi: https://doi.org/10.1016/j.yjmcc.2017.08.014Burgos JI, Yeves AM, Barrena JP, et al. Nitric oxide and CaMKII: Critical steps in the cardiac contractile response To IGF-1 and swim training. J Mol Cell Cardiol. 2017;112(8):16-26. doi: https://doi.org/10.1016/j.yjmcc.2017.08.014Neri Serneri GG, Boddi M, Modesti PA, et al. Increased cardiac sympathetic activity and insulin-like growth factor-I formation are associated with physiological hypertrophy in athletes. Circ Res. 2001;89(11):977-982. doi: https://doi.org/10.1161/hh2301.100982Neri Serneri GG, Boddi M, Modesti PA, et al. Increased cardiac sympathetic activity and insulin-like growth factor-I formation are associated with physiological hypertrophy in athletes. Circ Res. 2001;89(11):977-982. doi: https://doi.org/10.1161/hh2301.100982Juul A, Scheike T, Davidsen M, et al. Low serum insulinlike growth factor I is associated with increased risk of ischemic heart disease: a population-based case-control study. Circulation. 2002;106(8):939-944. doi: https://doi.org/10.1161/01.cir.0000027563.44593.ccJuul A, Scheike T, Davidsen M, et al. Low serum insulinlike growth factor I is associated with increased risk of ischemic heart disease: a population-based case-control study. Circulation. 2002;106(8):939-944. doi: https://doi.org/10.1161/01.cir.0000027563.44593.ccRuidavets JB, Luc G, Machez E, et al. Effects of insulin-like growth factor 1 in preventing acute coronary syndromes: The PRIME study. Atherosclerosis. 2011;218(2):464-469. doi: https://doi.org/10.1016/j.atherosclerosis.2011.05.034Ruidavets JB, Luc G, Machez E, et al. Effects of insulin-like growth factor 1 in preventing acute coronary syndromes: The PRIME study. Atherosclerosis. 2011;218(2):464-469. doi: https://doi.org/10.1016/j.atherosclerosis.2011.05.034Saber H, Himali JJ, Beiser AS, et al. Serum insulinlike growth factor 1 and the risk of ischemic stroke: The framingham study. stroke. 2017;48(7):1760-1765. doi: https://doi.org/10.1161/STROKEAHA.116.016563Saber H, Himali JJ, Beiser AS, et al. Serum insulinlike growth factor 1 and the risk of ischemic stroke: The framingham study. stroke. 2017;48(7):1760-1765. doi: https://doi.org/10.1161/STROKEAHA.116.016563Loeser RF. Growth factor regulation of chondrocyte integrins. Differential effects of insulin-like growth factor 1 and transforming growth factor beta on alpha 1 beta 1 integrin expression and chondrocyte adhesion to type VI collagen. Arthritis Rheum. 1997;40(2):270-276. doi: https://doi.org/10.1002/art.1780400211Loeser RF. Growth factor regulation of chondrocyte integrins. Differential effects of insulin-like growth factor 1 and transforming growth factor beta on alpha 1 beta 1 integrin expression and chondrocyte adhesion to type VI collagen. Arthritis Rheum. 1997;40(2):270-276. doi: https://doi.org/10.1002/art.1780400211Loeser RF, Shanker G, Carlson CS, et al. Reduction in the chondrocyte response to insulin-like growth factor 1 in aging and osteoarthritis: studies in a non-human primate model of naturally occurring disease. Arthritis Rheum. 2000;43(9):2110-2120. doi: https://doi.org/10.1002/1529-0131(200009)43:9<2110::AID-ANR23>3.0.CO;2-ULoeser RF, Shanker G, Carlson CS, et al. Reduction in the chondrocyte response to insulin-like growth factor 1 in aging and osteoarthritis: studies in a non-human primate model of naturally occurring disease. Arthritis Rheum. 2000;43(9):2110-2120. doi: https://doi.org/10.1002/1529-0131(200009)43:9<2110::AID-ANR23>3.0.CO;2-UNazli SA, Loeser RF, Chubinskaya S, et al. High fat-diet and saturated fatty acid palmitate inhibits IGF-1 function in chondrocytes. Osteoarthritis Cartilage. 2017;25(9):1516-1521. doi: https://doi.org/10.1016/j.joca.2017.05.011Nazli SA, Loeser RF, Chubinskaya S, et al. High fat-diet and saturated fatty acid palmitate inhibits IGF-1 function in chondrocytes. Osteoarthritis Cartilage. 2017;25(9):1516-1521. doi: https://doi.org/10.1016/j.joca.2017.05.011Rico-Llanos GA, Becerra J, Visser R. Insulin-like growth factor-1 (IGF-1) enhances the osteogenic activity of bone morphogenetic protein-6 (BMP-6) in vitro and in vivo, and together have a stronger osteogenic effect than when IGF-1 is combined with BMP-2. J Biomed Mater Res A. 2017;105(7):1867-1875. doi: https://doi.org/10.1002/jbm.a.36051Rico-Llanos GA, Becerra J, Visser R. Insulin-like growth factor-1 (IGF-1) enhances the osteogenic activity of bone morphogenetic protein-6 (BMP-6) in vitro and in vivo, and together have a stronger osteogenic effect than when IGF-1 is combined with BMP-2. J Biomed Mater Res A. 2017;105(7):1867-1875. doi: https://doi.org/10.1002/jbm.a.36051Harvey S, Martinez-Moreno CG. Growth hormone: therapeutic possibilities-an overview. Int J Mol Sci. 2018;19(7):2015. doi: https://doi.org/10.3390/ijms19072015Harvey S, Martinez-Moreno CG. Growth hormone: therapeutic possibilities-an overview. Int J Mol Sci. 2018;19(7):2015. doi: https://doi.org/10.3390/ijms19072015Луценко А.С., Нагаева Е.В., Белая Ж.Е., и др. Современные аспекты диагностики и лечения СТГ-дефицита взрослых // Проблемы эндокринологии. — 2019. — Т. 65. — №5. — С. 373-388. doi: https://doi.org/10.14341/probl10322Lutsenko AS, Nagaeva EV, Belaya ZhE, et al. Current aspects of diagnosis and treatment of adult GH-deficiency. Problems of Endocrinology. 2019;65(5):373-388. (In Russ.)]. doi: https://doi.org/10.14341/probl10322Kamil G, Karolina S, Aleksandra S, et al. Alterations in stem cell populations in igf-1 deficient pediatric patients subjected to mecasermin (Increlex) treatment. Stem Cell Rev Rep. 2023;19(2):392-405. doi: https://doi.org/10.1007/s12015-022-10457-2Kamil G, Karolina S, Aleksandra S, et al. Alterations in stem cell populations in igf-1 deficient pediatric patients subjected to mecasermin (Increlex) treatment. Stem Cell Rev Rep. 2023;19(2):392-405. doi: https://doi.org/10.1007/s12015-022-10457-2Xing T, Xu Y, Li J, et al. Associations between insulin-like growth factor-1 standard deviation score and overall nutritional parameters in patients with maintenance hemodialysis: a cross-sectional study. Int Urol Nephrol. 2023;43(9):2110-2120. doi: https://doi.org/10.1007/s11255-023-03526-zXing T, Xu Y, Li J, et al. Associations between insulin-like growth factor-1 standard deviation score and overall nutritional parameters in patients with maintenance hemodialysis: a cross-sectional study. Int Urol Nephrol. 2023;43(9):2110-2120. doi: https://doi.org/10.1007/s11255-023-03526-zAlizadeh Pahlavani H. Exercise therapy for people with sarcopenic obesity: myokines and adipokines as effective actors. Front Endocrinol (Lausanne). 2022;13(9):2110-2120. doi: https://doi.org/10.3389/fendo.2022.811751Alizadeh Pahlavani H. Exercise therapy for people with sarcopenic obesity: myokines and adipokines as effective actors. Front Endocrinol (Lausanne). 2022;13(9):2110-2120. doi: https://doi.org/10.3389/fendo.2022.811751Hadem IKH, Sharma R. Differential regulation of hippocampal IGF-1-associated signaling proteins by dietary restriction in aging mouse. Cell Mol Neurobiol. 2017;37(6):985-993. doi: https://doi.org/10.1007/s10571-016-0431-7Hadem IKH, Sharma R. Differential regulation of hippocampal IGF-1-associated signaling proteins by dietary restriction in aging mouse. Cell Mol Neurobiol. 2017;37(6):985-993. doi: https://doi.org/10.1007/s10571-016-0431-7Gram IT, Norat T, Rinaldi S, et al. Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women. Int J Obes (Lond). 2006;30(11):1623-1631. doi: https://doi.org/10.1038/sj.ijo.0803324Gram IT, Norat T, Rinaldi S, et al. Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women. Int J Obes (Lond). 2006;30(11):1623-1631. doi: https://doi.org/10.1038/sj.ijo.0803324Lifshitz F. Nutrition and growth. J Clin Res Pediatr Endocrinol. 2009;1(4):157-163. doi: https://doi.org/10.4274/jcrpe.v1i4.39Lifshitz F. Nutrition and growth. J Clin Res Pediatr Endocrinol. 2009;1(4):157-163. doi: https://doi.org/10.4274/jcrpe.v1i4.39Chromiak JA, Antonio J. Use of amino acids as growth hormonereleasing agents by athletes. Nutrition. 2002;18(7-8):657-661. doi: https://doi.org/10.1016/s0899-9007(02)00807-9Chromiak JA, Antonio J. Use of amino acids as growth hormonereleasing agents by athletes. Nutrition. 2002;18(7-8):657-661. doi: https://doi.org/10.1016/s0899-9007(02)00807-9Alba-Roth J, Müller OA, Schopohl J, von Werder K. Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. J Clin Endocrinol Metab. 1988;67(6):1186-1189. doi: https://doi.org/10.1210/jcem-67-6-1186Alba-Roth J, Müller OA, Schopohl J, von Werder K. Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. J Clin Endocrinol Metab. 1988;67(6):1186-1189. doi: https://doi.org/10.1210/jcem-67-6-1186Livesey G, Taylor R, Hulshof T, Howlett J. Glycemic response and health--a systematic review and meta-analysis: relations between dietary glycemic properties and health outcomes. Am J Clin Nutr. 2008;87(1):258S-268S. doi: https://doi.org/10.1093/ajcn/87.1.258SLivesey G, Taylor R, Hulshof T, Howlett J. Glycemic response and health--a systematic review and meta-analysis: relations between dietary glycemic properties and health outcomes. Am J Clin Nutr. 2008;87(1):258S-268S. doi: https://doi.org/10.1093/ajcn/87.1.258SSuminski RR, Robertson RJ, Goss FL, et al. Acute effect of amino acid ingestion and resistance exercise on plasma growth hormone concentration in young men. Int J Sport Nutr. 1997;7(1):48-60. doi: https://doi.org/10.1123/ijsn.7.1.48Suminski RR, Robertson RJ, Goss FL, et al. Acute effect of amino acid ingestion and resistance exercise on plasma growth hormone concentration in young men. Int J Sport Nutr. 1997;7(1):48-60. doi: https://doi.org/10.1123/ijsn.7.1.48

The authors declare that there are no conflicts of interest present.