زمینهوهدف:سالمندی با کاهش عملکرد نورونی و افت فاکتورهای نوروتروفیک همراه است. باوجود تأثیر مجزای تمرین و کوئرستین در فاکتورهای عصبی، تأثیر ترکیبی آن‌ها در فاکتور رشد عصبی (NGF) و فاکتور نوروتروفیک مشتق از سلول‌های گلیال (GDNF) در سالمندان و مزیت افزایشی آن در مقایسه با تمرین به‌تنهایی، ناشناخته است. ازاین‌رو، هدف این پژوهش بررسی اثر تمرین تناوبی با شدت متوسط (MIIT) و مکمل کوئرستین بر سطوح NGF و GDNF در مردان سالمند بود. روشبررسی:در پژوهش نیمه‌تجربی حاضر، چهل مرد سالمند (60 تا 75 سال) به‌صورت تصادفی در چهار گروه MIIT، مکمل، تمرین+مکمل و کنترل قرار گرفتند (هر گروه ده نفر). برنامة تمرینی به‌مدت هشت هفته MIIT، سه جلسه در هفته (هشت تا دوازده تناوب دو تا سه‌دقیقه‌ای با شدت 70 تا 80 درصد ضربان قلب بیشینه با استراحت فعال) اجرا شد و گروه‌های مکمل روزانه ۵۰۰ میلی‌گرم کوئرستین دریافت کردند. سطوح سرمی NGFو GDNF با روش الایزا اندازه‌گیری شدند. یافته‌ها:نتایج نشان داد سطوح NGF در گروه‌های تمرین و تمرین+مکمل به‌ترتیب حدود ۱۴ و ۱۷ درصد افزایش و سطوح GDNF در مقایسه با گروه کنترل و مکمل حدود ۱۵ و ۱۰ درصد افزایش یافت (05/0>P). بااین‌حال، بین دو گروه تمرینی با و بدون مکمل تفاوت معنی‌داری مشاهده نشد (05/0<P). مصرف کوئرستین به‌تنهایی در NGF و GDNF اثر معنی‌داری نداشت (05/0<P). نتیجه‌گیری:MIIT با افزایش معنی‌دار NGF و GDNF، رویکردی عملی برای بهبود شاخص‌های نوروتروفیک و حمایت از نورون‌های دوپامینرژیک در سالمندان است؛ درحالی‌که افزودن کوئرستین در مقایسه با تمرین به‌تنهایی، مزیت افزایشی معنی‌داری ندارد.
1.García-Domínguez M. Pathological and inflammatory consequences of aging. Biomolecules. 2025 Mar ;15 (3): 404. [10.3390/biom15030404] [PMID]
2.López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan ;186(2):243-78. [1016/j.cell. 2022.11.001] [PMID]
3.Navakkode S, Kennedy BK. Neural ageing and synaptic plasticity: prioritizing brain health in healthy longevity. Frontiers in Aging Neuroscience. 2024 Aug ;16:1428244. [10.3389/fnagi.2024.1428244] [PMID]
4.Xiong F, Xiao B-l, Wang Q, Liu K, Wu H-w, Jing C, et al. Nerve growth factor: what can surgeons and oncologists learn from a neurological and psychological biomarker? Molecular Medicine. 2025 Aug ;31(1):27. [10.1186/s10020-025-01333-z] [PMID]
5.Kim M-S, Shutov LP, Gnanasekaran A, Lin Z, Rysted JE, Ulrich JD, Usachev YM. Nerve growth factor (NGF) regulates activity of nuclear factor of activatedt-cells (nfat) in neurons via the phosphatidylinositol 3-kinase (pi3k)-akt-glycogen synthase kinase 3β (gsk3β) pathway. Journal of Biological Chemistry. 2014 Nov ;289 (45):31349-60. [10.1074/jbc.M114.587188] [PMID].
6.Bukhari A, Shaikh A, Salman W, Bhatti F, Malik W, Minhas M, et al. Pathophysiological role of nerve growth factor (NGF) in asthma: insights into airway inflammation, remodeling, and neural regulation in intensive care settings. Anaesth. pain intensive care. 2025 June ; 29 (3): 681-689. [10.35975/apic.v29i3.2778]
7.Khan MN, Choudhary D, Mehan S, Khan Z, Gupta GD, Narula AS. Molecular mechanisms of gdnf/gfra1/ret and pi3k/akt/erk signaling interplay in neuroprotection: therapeutic strategies for treating neurologic]al disorders. Neuropeptides. 2025 Jun ;111:102516. [10.1016/ j. npep. 2025.102516] [PMID].
8.Mol P, Balaya RDA, Dagamajalu S, Babu S, Chandrasekaran P, Raghavan R, et al. A network map of gdnf/ret signaling pathway in physiological and pathological conditions. Journal of Cell Communication and Signaling. 2023 Sep ;17(3):1089-95. [10.1007/s12079-023-00726-1] [PMID]
9.Budni J, Bellettini-Santos T, Mina F, Garcez ML, Zugno AI. The involvement of bdnf, ngf and gdnf in aging and alzheimer’s disease. Aging and disease. 2015 Oct ;6(5):331. [10.14336/AD.2015.0825] [PMID]
10.Mansoor M, Ibrahim A, Hamide A, Tran T, Candreva E, Baltaji J. Exercise-induced neuroplasticity: adaptive mechanisms and preventive potential in neurodegenerative disorders. Physiologia. 2025 April ;5(2):13. [10.3390/physiologia5020013]
11.Clemente-Suárez VJ, Rubio-Zarapuz A, Belinchón-deMiguel P, Beltrán-Velasco AI, Martín-Rodríguez A, Tornero-Aguilera JF. Impact of physical activity on cellular metabolism across both neurodegenerative and general neurological conditions: a narrative review. Cells. 2024 Nov ;13(23):1940. [10.3390/ cells13231940] [PMID]
12.Dai Y, Dou X, Nie B, Sun Y, Chen P, Fu C, et al. Exercise and the organ-brain axis: Regulation of neurological disorders by emerging exerkines. Pharmacological Research. 2025 Sep ;219:107913. [10.1016/j. phrs. 2025.107913] [PMID]
Jost Z, Rozynkowska A, Głąb M, Sitkiewicz A, Goiko M, Laskowski R, et al. Acute and chronic effects of high-intensity interval training on selected exerkine secretion in health, disease, and aging: a systematic review. Frontiers in Physiology. 2025 Jan ;16: 1733269. [10. 3389/fphys.2025.1733269] [PMID].
13.Coswig VS, Barbalho M, Raiol R, Del Vecchio FB, Ramirez-Campillo R, Gentil P. Effects of high vs moderate-intensity intermittent training on functionality, resting heart rate and blood pressure of elderly women. Journal of translational medicine. 2020 Feb ;18(1):88. [10.1186/s12967-020-02261-8] [PMID]
14.Poon ET-C, Wongpipit W, Ho RS-T, Wong SH-S. Interval training versus moderate-intensity continuous training for cardiorespiratory fitness improvements in middle-aged and older adults: a systematic review and meta-analysis. Journal of Sports Sciences. 2021 Sep ;39(17):1996-2005.[10.1080/02640414. 2021. 1912 453] [PMID]
15.Di Benedetto S, Müller L, Wenger E, Düzel S, Pawelec G. Contribution of neuroinflammation and immunity to brain aging and the mitigating effects of physical and cognitive interventions. Neuroscience & Biobehavioral Reviews. 2017 Apr;75:114-28. [10.1016/j.neubiorev. 2017.01.044] [PMID]
16.Mattson MP, Arumugam TV. Hallmarks of brain aging: adaptive and pathological modification by metabolic states. Cell metabolism. 2018 Jun ;27(6):1176-99. [10.1016/j.cmet.2018.05.011] [PMID]
17.Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, et al. Quercetin, inflammation and immunity. Nutrients. 2016 Mar ;8(3):167. [10.3390/nu8030167] [PMID]
18.Dajas F. Life or death: neuroprotective and anticancer effects of quercetin. Journal of ethnopharmacology. 2012 Sep ;143(2):383-96. [10.1016/j.jep. 2012. 07.005]
19.Kressler J, Millard-Stafford M, Warren GL. Quercetin and endurance exercise capacity: a systematic review and meta-analysis. Medicine Science Sports Exerc. 2011 Dec;43(12):2396-404. [10.1249/MSS. 0b013 e318224 95 a7] [PMID]
20.Bazzucchi I, Patrizio F, Ceci R, Duranti G, Sgage. The effects of quercetin supplementation on eccentric exercise-induced muscle damage. Nutrients. 2019 Jan ;11(1):205. [10.3390/nu11010205] [PMID]
21.Stich S, Loch A, Park S-J, Häupl T, Ringe J, Sittinger M. Characterization of single cell derived cultures of periosteal progenitor cells to ensure the cell quality for clinical application. PLoS One. 2017 May ;12 (5):e0178560.[10.1371/journal.pone.0178560] [PMID]
22.Eston R, Reilly T. Kinanthropometry and exercise physiology laboratory manual: tests, procedures and data: volume two: physiology: Routledge; 2013 Mar. [PMID]
23.Jiménez-García JD, Hita-Contreras F, de la Torre-Cruz MJ, Aibar-Almazán A, Achalandabaso-Ochoa A, Fábrega-Cuadros R, et al. Effects of hiit and miit suspension training programs on sleep quality and fatigue in older adults: randomized controlled clinical trial. International journal of environmental research and public health. 2021 Jan ;18(3):1211. [10.3390/ ijerph1 803121] [PMID]
24.Chiang M-C, Tsai T-Y, Wang C-J. The potential benefits of quercetin for brain health: a review of anti-inflammatory and neuroprotective mechanisms. International journal of molecular sciences. 2023 Mar ;24(7):6328. [10.3390/ijms24076328] [PMID]
25.Zaplatic E, Bule M, Shah SZA, Uddin MS, Niaz K. Molecular mechanisms underlying protective role of quercetin in attenuating Alzheimer's disease. Life sciences. 2019 Aug ;224:109-19. [10.1016/ j.lfs. 2019. 116616] [PMID]
26.McCULLOUGH ML, Karanja NM, Lin P-H, Obarzanek E, Phillips KM, Laws RL, et al. Comparison of 4 nutrient databases with chemical composition data from the dietary approaches to stop hypertension trial. Journal of the American Dietetic Association. 1999 Aug ;99 (8):S45-S53.[10.1016/s0002-8223(99)00416-2] [PMID]
27.Bagheri R, Rashidlamir A, Motevalli MS, Elliott BT, Mehrabani J, Wong A. Effects of upper-body, lower-body, or combined resistance training on the ratio of follistatin and myostatin in middle-aged men. European journal of applied physiology. 2019 Sep ;119(9):1921-31. [10.1007/s00421-019-04180-z] [PMID]
28.Yaghoubi A, Elhami A. The effect of 6 weeks of high intensity circuit resistance training on plasma level of brain-derived neurotrophic factor in inactive men. Sport Physiology & Management Investigations. 2018;9(4):69-78. [PMID]
29.Babaei P, Azali Alamdari K. Effects of endurance training and detraining on serum BDNF and memory performance in middle aged males with metabolic syndrome. Iranian Journal of Endocrinology and Metabolism. 2013;15(2):132-42. [PMID]
30.Sanada F, Taniyama Y, Muratsu J, Otsu R, Shimizu H, Rakugi H, et al. Source of chronic inflammation in aging. Frontiers in cardiovascular medicine. 2018 Feb ;5:12. [10.3389/fcvm.2018.00012] [PMID]
32.Vianney J-M, Mccullough MJ, Gyorkos AMSpitsbergen JM. Exercise-dependent regulation of glial cell line-derived neurotrophic factor (GDNF) expression in skeletal muscle and its importance for the neuromuscular system. Frontiers in biology. 2013;8(1):101-8. [PMID]
33.Naser AA, Dehkordi KJ, Radhi MN, Taghian F, Chitsaz A. The effect of multimodal exercise on the levels of bdnf and gdnf in patients with parkinson’s disease. International Journal of Preventive Medicine. 2025 May; 16:35. [10.4103/ijpvm.ijpvm_353_24] [PMID]
34.da Silva PGC, Domingues DD, De Carvalho LA, Allodi S, Correa CL. Neurotrophic factors in Parkinson's disease are regulated by exercise: evidence-based practice. Journal of the Neurological Sciences. 2016 Apr ;363:5-15. [10.1016/ j.jns.2016.02.017] [PMID]
35.Soke F, Guclu-Gunduz A, Kocer B, Fidan I, Keskinoglu P. Task-oriented circuit training combined with aerobic training improves motor performance and balance in people with Parkinson′ s Disease. Acta Neurologica Belgica. 2021 Nov ;121(2):535-43. [10.1007/s13760-019 -01247-8] [PMID]
36.Rotondo R, Proietti S, Perluigi M, Padua E, Stocchi F, Fini M, et al. Physical activity and neurotrophic factors aspotential drivers of neuroplasticity in Parkinson’s Disease: A systematic review and meta-analysis. Ageing Research Reviews. 2023 Dec ;92:102089. [10.1016 /j. arr.2023.102089] [PMID]
37.Cotman CW, Berchtold NC, Christie L-A. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends in neurosciences. 2007 Oct ;30(9):464-72. [10.1016/j.tins.2007.06.011] [PMID]
38.Moradi M, Yaghoubi A, Jalilvand M-R. The effect of intense continuous and interval training on the levels of brain-derived neurotrophic factor (bdnf) and tumor necrosis factor alpha (tnf-α) in hippocampus of old rats. Journal of Isfahan Medical School. 2021;39(628):414-20. [10.22122/jims. v39i628. 14076]
39.Górna S, Podgórski T, Kleka P, Domaszewska K. Effects of different intensities of endurance training on Neurotrophin levels and functional and cognitive outcomes in post-Ischaemic stroke adults: a randomised clinical trial. International Journal of Molecular Sciences. 2025 Mar ;26(6):2810. [10.3390/ ijms26062810] [PMID]
40.Casuso RA, Martínez-López EJ, Hita-Contreras F, Camiletti-Moiron D, Martínez-Romero R, Cañuelo A, et al. The combination of oral quercetin supplementation and exercise prevents brain mitochondrial biogenesis. Genes & nutrition. 2014 Sep ;9(5):420. [10.1007 /s122 63-014-0420-8] [PMID]
41.Sgrò P, Ceci R, Lista M, Patrizio F, Sabatini S, Felici F, et al. Quercetin modulates IGF-I and IGF-II levels after eccentric exercise-induced muscle-damage: A placebo-controlled study. Frontiers in endocrinology. 2021 Nov ;12:745959. [10.3389/fendo.2021.745959] [PMID]
42.Nishikawa T, Takeda R, Ueda S, Igawa K, Hirono T, Okudaira M, et al. Quercetin ingestion alters motor unit behavior and enhances improvement in muscle strength following resistance training in older adults: a randomized, double-blind, controlled trial. European Journal of Nutrition. 202 Mar 5;64(3):117. [10.1007/ s00394-025-03634-9] [PMID]
43.Molaei A, Hatami H, Dehghan G, Sadeghian R, Khajehnasiri N. Synergistic effects of quercetin and regular exercise on the recovery of spatial memory and reduction of parameters of oxidative stress in animal model of Alzheimer's disease. EXCLI journal. 2020 May ;19:596. [10.17179/excli2019-2082] [PMID]
44.Ghasemi E, Nayebifar S. The effect of quercetin supplementation on the responses of sirtuin-1brain-derived neurotrophic factor and insulin-like growth factor-1 to high intensity interval exercise and continuous exercise in female athletes. Journal of Sport & Exercise Physiology (JSEP)/Fīziyuluzhī-i Varzish va Fa̒āliyyat-i Badanī. 2024 Oct ;17(4). [10.48308/ joeppa. 2024. 236069.1269]
