Health benefits of physical activity: What role does skeletal muscle-organ crosstalk play?

Scott K. Powers , Erica Goldstein , Ronette Lategan-Potgieter , Matthew Schrager , Michele Skelton , Haydar Demirel

Sports Medicine and Health Science ›› 2025, Vol. 7 ›› Issue (5) : 329 -340.

PDF (1038KB)
Sports Medicine and Health Science ›› 2025, Vol. 7 ›› Issue (5) : 329 -340. DOI: 10.1016/j.smhs.2025.02.010
Review article
research-article

Health benefits of physical activity: What role does skeletal muscle-organ crosstalk play?

Author information +
History +
PDF (1038KB)

Abstract

The observation that physical activity (PA) reduces the risk of coronary heart disease dates back more than 70 years ago and it is now established that regular PA reduces all-cause mortality, in part, by reducing the risk of numerous chronic diseases including coronary heart disease, stroke, cancer, type 2 diabetes, and Alzheimer's disease. During the past decade the increased use of activity tracking devices has significantly improved our understanding of the dose-response relationships between PA and all-cause mortality. Further, our appreciation of the impact that prolonged sitting has on all-cause mortality has increased. Moreover, new research provides key insight into the signaling mechanisms that connect PA to the reduced risk of disease in multiple organ systems. Therefore, given the recent advances in the study of PA and all-cause mortality, it is an appropriate time to review the latest evidence on this topic as well as the mechanisms responsible for the PA-induced protection against all-cause mortality. Therefore, this review will summarize recent data on the dose-response association between PA on all-cause mortality and the negative impact that sedentary behavior has on all-cause mortality. Further, we also highlight potential mechanisms linking PA with the reduced risk of developing several chronic diseases. Finally, we conclude with a brief discussion of the emerging evidence that the health benefits associated with PA are derived, in part, from skeletal muscle-organ crosstalk involving muscle produced hormones (myokines) that exert their effects in either an autocrine, paracrine, or endocrine manner.

Keywords

Exercise / Myokines / Coronary heart disease / Diabetes / Cancer / Alzheimer's disease

Cite this article

Download citation ▾
Scott K. Powers, Erica Goldstein, Ronette Lategan-Potgieter, Matthew Schrager, Michele Skelton, Haydar Demirel. Health benefits of physical activity: What role does skeletal muscle-organ crosstalk play?. Sports Medicine and Health Science, 2025, 7(5): 329-340 DOI:10.1016/j.smhs.2025.02.010

登录浏览全文

4963

注册一个新账户 忘记密码

CRediT authorship contribution statement

Scott K. Powers: Writing - review & editing, Writing - original draft, Investigation, Conceptualization. Erica Goldstein: Writing - review & editing, Investigation. Ronette Lategan-Potgieter: Writing - review & editing. Matthew Schrager: Writing - review & editing. Michele Skelton: Writing - review & editing. Haydar Demirel: Writing - review & editing.

Artificial intelligence

Artificial intelligence was not used in form in the development of this manuscript.

Funding

No funding sources were available for this review.

Declaration of competing interest

Scott K. Powers is an Editorial Board Member for Sports Medicine and Health Science and was not involved in the editorial review or the de-cision to publish this article. The authors of this review declare no con-flicts of interest.

References

[1]

Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Publ Health Rep. 1985; 100(2):126-131.

[2]

Morris JN, Heady JA, Raffle PA, Roberts CG, Parks JW. Coronary heart-disease and physical activity of work. Lancet. 1953; 262(6795):1053-1057.https://doi.org/10.1016/s0140-6736(53)90665-5.

[3]

Blair SN, Kampert JB,Kohl 3rd HW, Barlow CE, Macera CA, Paffenbarger Jr RS, Gibbons LW. Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women. JAMA. 1996; 276(3):205-210. https://www.ncbi.nlm.nih.gov/pubmed/8667564.

[4]

Blair SN,Kohl HW 3rd, Barlow CE, Paffenbarger RS Jr, Gibbons LW, Macera CA. Changes in physical fitness and all-cause mortality. A prospective study of healthy and unhealthy men. JAMA. 1995; 273(14):1093-1098. https://www.ncbi.nlm.nih.gov/p ubmed/7707596.

[5]

Ekelund U, Dalene KE, Tarp J, Lee IM. Physical activity and mortality: what is the dose response and how big is the effect? Br J Sports Med. 2020; 54(19):1125-1126. https://doi.org/10.1136/bjsports-2019-101765.

[6]

Ekelund U, Hildebrand M, Collings PJ. Physical activity, sedentary time and adiposity during the first two decades of life. Proc Nutr Soc. 2014; 73(2):319-329. https://doi.org/10.1017/S0029665114000019.

[7]

Ekelund U, Sanchez-Lastra MA, Dalene KE, Tarp J. Dose-response associations, physical activity intensity and mortality risk: a narrative review. J Sport Health Sci. 2024; 13(1):24-29. https://doi.org/10.1016/j.jshs.2023.09.006.

[8]

Ekelund U, Steene-Johannessen J, Brown WJ, Fagerland MW, Owen N, Powell KE, Bauman A, Lee IM,Lancet Physical Activity Series 2 Executive, C., Lancet Sedentary Behaviour Working, G.. Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women. Lancet. 2016; 388(10051): 1302-1310. https://doi.org/10.1016/S0140-6736(16)30370-1.

[9]

Ekelund U, Ward HA, Norat T, Luan J, May AM, Weiderpass E, Sharp SJ, Overvad K, Ostergaard JN, Tjonneland A, Johnsen NF, Mesrine S, Fournier A, Fagherazzi G, Trichopoulou A, Lagiou P, Trichopoulos D, Li K, Kaaks R, Riboli E. Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Am J Clin Nutr. 2015; 101(3):613-621. https://doi.org/10.3 945/ajcn.114.100065.

[10]

El-Kotob R, et al. Resistance training and health in adults: an overview of systematic reviews. Appl Physiol Nutr Metabol. 2020; 45(10):S165-S 179 (Suppl. 2).

[11]

Paffenbarger Jr RS, et al. Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med. 1986; 314(10):605-613.

[12]

Arvidsson D, Fridolfsson J, Borjesson M. Measurement of physical activity in clinical practice using accelerometers. J Intern Med. 2019; 286(2):137-153.

[13]

Troiano RP, et al. Evolution of accelerometer methods for physical activity research. Br J Sports Med. 2014; 48(13):1019-1023.

[14]

Bull FC, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020; 54(24):1451-1462.

[15]

Saint-Maurice PF, et al. Volume of light versus moderate-to-vigorous physical activity: similar benefits for all-cause mortality? J Am Heart Assoc. 2018; 7(7): e008815.

[16]

Ekelund U, et al. Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis. Br Med J. 2019;366:l4570.

[17]

Saint-Maurice PF, et al. Moderate-to-Vigorous physical Activity and all-cause mortality: do bouts matter? J Am Heart Assoc. 2018; 7(6):e007678.

[18]

Shailendra P, et al. Weight training and risk of all-cause, cardiovascular disease and cancer mortality among older adults. Int J Epidemiol. 2024; 53(3):dyae074.

[19]

Ekelund U, et al. Do the associations of sedentary behaviour with cardiovascular disease mortality and cancer mortality differ by physical activity level? A systematic review and harmonised meta-analysis of data from 850 060 participants. Br J Sports Med. 2019; 53(14):886-894.

[20]

Patterson R, et al. Sedentary behaviour and risk of all-cause, cardiovascular and cancer mortality, and incident type 2 diabetes: a systematic review and dose response meta-analysis. Eur J Epidemiol. 2018; 33(9):811-829.

[21]

Stamatakis E, et al. Does strength-promoting exercise confer unique health benefits? A pooled Analysis of Data on 11 population cohorts with all-cause, cancer, and cardiovascular mortality endpoints. Am J Epidemiol. 2018; 187(5):1102-1112.

[22]

Chau JY, et al. Daily sitting time and all-cause mortality: a meta-analysis. PLoS One. 2013; 8(11):e80000.

[23]

Kim Y, et al. Association between various sedentary behaviours and all-cause, cardiovascular disease and cancer mortality: the Multiethnic Cohort Study. Int J Epidemiol. 2013; 42(4):1040-1056.

[24]

Crawford CK, et al. Prolonged standing reduces fasting plasma triglyceride but does not influence postprandial metabolism compared to prolonged sitting. PLoS One. 2020; 15(2):e0228297.

[25]

Kim IY, et al. Prolonged sitting negatively affects the postprandial plasma triglyceride-lowering effect of acute exercise. Am J Physiol Endocrinol Metab. 2016; 311(5):E891-E898.

[26]

Kim IY, et al. Effects of moderate- and intermittent low-intensity exercise on postprandial lipemia. Med Sci Sports Exerc. 2014; 46(10):1882-1890.

[27]

Benatti FB, Ried-Larsen M. The effects of breaking up prolonged sitting time: a review of experimental studies. Med Sci Sports Exerc. 2015; 47(10):2053-2061.

[28]

Dunstan DW, et al. Breaking up prolonged sitting reduces postprandial glucose and insulin responses. Diabetes Care. 2012; 35(5):976-983.

[29]

Arem H, et al. Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship. JAMA Intern Med. 2015; 175(6):959-967.

[30]

Dankel SJ, Loenneke JP, Loprinzi PD. Dose-dependent association between muscle-strengthening activities and all-cause mortality: prospective cohort study among a national sample of adults in the USA. Arch Cardiovasc Dis. 2016; 109(11):626-633.

[31]

Kraus WE, et al. Physical activity, all-Cause and cardiovascular mortality, and cardiovascular disease. Med Sci Sports Exerc. 2019; 51(6):1270-1281.

[32]

Paffenbarger Jr RS, Wing AL, Hyde RT. Physical activity as an index of heart attack risk in college alumni. Am J Epidemiol. 1978; 108(3):161-175.

[33]

Hansen BH, et al. Accelerometer-determined physical activity in adults and older people. Med Sci Sports Exerc. 2012; 44(2):266-272.

[34]

Matthews CE, et al. Amount of time spent in sedentary behaviors in the United States, 2003-2004. Am J Epidemiol. 2008; 167(7):875-881.

[35]

Ekelund U, et al. Joint associations of accelero-meter measured physical activity and sedentary time with all-cause mortality: a harmonised meta-analysis in more than 44 000 middle-aged and older individuals. Br J Sports Med. 2020; 54(24): 1499-1506.

[36]

Sagelv EH, et al. Device-measured physical activity, sedentary time, and risk of all-cause mortality: an individual participant data analysis of four prospective cohort studies. Br J Sports Med. 2023; 57(22):1457-1463.

[37]

WHO. Leading Causes of Death in 2021 Globally. WHO; 2021.

[38]

Prevention CfDCa. Deaths: Leading causes for. 2021;2021:10.

[39]

Perry AS, et al. Physical activity over the lifecourse and cardiovascular disease. Circ Res. 2023; 132(12):1725-1740.

[40]

Blond K, et al. Association of high amounts of physical activity with mortality risk: a systematic review and meta-analysis. Br J Sports Med. 2020; 54(20):1195-1201.

[41]

Mora S, et al. Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation. 2007; 116(19):2110-2118.

[42]

Pescatello LS, et al. Physical activity to prevent and treat hypertension: a systematic review. Med Sci Sports Exerc. 2019; 51(6):1314-1323.

[43]

Liu X, et al. Dose-response association between physical Activity and incident hypertension: a systematic Review and meta-Analysis of cohort studies. Hypertension. 2017; 69(5):813-820.

[44]

Pinckard K, Baskin KK, Stanford KI. Effects of exercise to improve cardiovascular health. Front Cardiovasc Med. 2019;6:69.

[45]

Barone Gibbs B, et al. Physical activity as a critical component of first-line treatment for elevated blood pressure or cholesterol: who, what, and how?: a scientific statement from the American heart association. Hypertension. 2021; 78(2):e26-e37.

[46]

Mann S, Beedie C, Jimenez A. Differential effects of aerobic exercise, resistance training and combined exercise modalities on cholesterol and the lipid profile: review, synthesis and recommendations. Sports Med. 2014; 44(2):211-221.

[47]

Bandeali S, Farmer J. High-density lipoprotein and atherosclerosis: the role of antioxidant activity. Curr Atheroscler Rep. 2012; 14(2):101-107.

[48]

Durstine JL, et al. Lipids, lipoproteins, and exercise. J Cardiopulm Rehabil. 2002; 22(6):385-398.

[49]

Gordon B, Chen S, Durstine JL. The effects of exercise training on the traditional lipid profile and beyond. Translat J Amer College Sports Med. 2016;1:159-164.

[50]

Powell-Wiley TM, et al. Obesity and cardiovascular disease: a scientific statement from the American heart association. Circulation. 2021; 143(21):e984-e1010.

[51]

Swift DL, et al. The role of exercise and physical activity in weight loss and maintenance. Prog Cardiovasc Dis. 2014; 56(4):441-447.

[52]

Petridou A, Siopi A, Mougios V. Exercise in the management of obesity. Metabolism. 2019;92:163-169.

[53]

Oppert JM, et al. Exercise training in the management of overweight and obesity in adults: synthesis of the evidence and recommendations from the European association for the study of obesity physical activity working group. Obes Rev. 2021; 22(suppl 4):e13273. Suppl 4.

[54]

Pedersen BK. The diseasome of physical inactivity-and the role of myokines in muscle-fat cross talk. J Physiol. 2009; 587(Pt 23):5559-5568.

[55]

Pedersen BK. The physiology of optimizing health with a focus on exercise as medicine. Annu Rev Physiol. 2019;81:607-627.

[56]

Quinn LS, et al. Oversecretion of interleukin-15 from skeletal muscle reduces adiposity. Am J Physiol Endocrinol Metab. 2009; 296(1):E191-E202.

[57]

Nielsen AR, et al. Association between interleukin-15 and obesity: interleukin-15 as a potential regulator of fat mass. J Clin Endocrinol Metab. 2008; 93(11):4486-4493.

[58]

Yargic MP, et al. Acute long-distance trail running increases serum IL-6, IL-15, and Hsp 72 levels. Appl Physiol Nutr Metabol. 2019; 44(6):627-631.

[59]

French JP, et al. Exercise-induced protection against myocardial apoptosis and necrosis: MnSOD, calcium-handling proteins, and calpain. FASEB J. 2008; 22(8): 2862-2871.

[60]

Hamilton KL, et al. Short-term exercise training can improve myocardial tolerance to I/R without elevation in heat shock proteins. Am J Physiol Heart Circ Physiol. 2001; 281(3):H1346-52.

[61]

Hamilton KL, et al. Exercise, antioxidants, and HSP72: protection against myocardial ischemia/reperfusion. Free Radic Biol Med. 2003; 34(7):800-809.

[62]

Powers SK, Quindry JC, Kavazis AN. Exercise-induced cardioprotection against myocardial ischemia-reperfusion injury. Free Radic Biol Med. 2008; 44(2):193-201.

[63]

Powers SK, et al. Mechanisms of exercise-induced cardioprotection. Physiology. 2014; 29(1):27-38.

[64]

Kavazis AN, et al. Exercise training induces a cardioprotective phenotype and alterations in cardiac subsarcolemmal and intermyofibrillar mitochondrial proteins. Am J Physiol Heart Circ Physiol. 2009; 297(1):H144-52.

[65]

Kavazis AN, et al. Exercise induces a cardiac mitochondrial phenotype that resists apoptotic stimuli. Am J Physiol Heart Circ Physiol. 2008; 294(2):H928-35.

[66]

Lee Y, et al. Exercise protects cardiac mitochondria against ischemia-reperfusion injury. Med Sci Sports Exerc. 2012; 44(3):397-405.

[67]

Powers SK, et al. Exercise-induced improvements in myocardial antioxidant capacity: the antioxidant players and cardioprotection. Free Radic Res. 2014; 48(1): 43-51.

[68]

Thomas R, et al. Why exercise has a crucial role in cancer prevention, risk reduction and improved outcomes. Br Med Bull. 2021; 139(1):100-119.

[69]

Moore SC, et al. Association of leisure-time physical activity with Risk of 26 Types of Cancer in 1.44 million adults. JAMA Intern Med. 2016; 176(6):816-825.

[70]

Holmes MD, et al. Physical activity and survival after breast cancer diagnosis. JAMA. 2005; 293(20):2479-2486.

[71]

Kenfield SA, et al. Physical activity and survival after prostate cancer diagnosis in the health professionals follow-up study. J Clin Oncol. 2011; 29(6):726-732.

[72]

Meyerhardt JA, et al. Physical activity and survival after colorectal cancer diagnosis. J Clin Oncol. 2006; 24(22):3527-3534.

[73]

Matthews CE, et al. Amount and intensity of leisure-time physical activity and lower cancer risk. J Clin Oncol. 2020; 38(7):686-697.

[74]

Wu Y, Zhang D, Kang S. Physical activity and risk of breast cancer: a meta-analysis of prospective studies. Breast Cancer Res Treat. 2013; 137(3):869-882.

[75]

Ashcraft KA, et al. Efficacy and mechanisms of aerobic exercise on cancer initiation, progression, and metastasis: a critical systematic review of in vivo preclinical data. Cancer Res. 2016; 76(14):4032-4050.

[76]

Pedersen L, Christensen JF, Hojman P. Effects of exercise on tumor physiology and metabolism. Cancer J. 2015; 21(2):111-116.

[77]

Jones LW, et al. Exercise and prognosis on the basis of clinicopathologic and molecular features in early-stage breast cancer: the LACE and pathways studies. Cancer Res. 2016; 76(18):5415-5422.

[78]

Morikawa T, et al. Association of CTNNB 1 (beta-catenin) alterations, body mass index, and physical activity with survival in patients with colorectal cancer. JAMA. 2011; 305(16):1685-1694.

[79]

Hojman P, et al. Molecular mechanisms linking exercise to cancer prevention and treatment. Cell Metab. 2018; 27(1):10-21.

[80]

Spanoudaki M, et al. Exercise as a promising agent against cancer: evaluating its anti-cancer molecular mechanisms. Cancers. 2023; 15(21):5135.

[81]

Emery A, et al. Reframing how physical activity reduces the incidence of clinically-diagnosed cancers: appraising exercise-induced immuno-modulation as an integral mechanism. Front Oncol. 2022;12:788113.

[82]

Wang Q, Zhou W. Roles and molecular mechanisms of physical exercise in cancer prevention and treatment. J Sport Health Sci. 2021; 10(2):201-210.

[83]

Dethlefsen C, et al. Exercise-induced catecholamines Activate the Hippo tumor suppressor Pathway to reduce Risks of breast cancer development. Cancer Res. 2017; 77(18):4894-4904.

[84]

Pedersen L, et al. Voluntary running suppresses tumor growth through epinephrine-and IL-6-dependent NK cell mobilization and redistribution. Cell Metab. 2016; 23(3): 554-562.

[85]

Idorn M, Hojman P. Exercise-dependent Regulation of NK Cells in cancer protection. Trends Mol Med. 2016; 22(7):565-577.

[86]

Wolf NK, Kissiov DU, Raulet DH. Roles of natural killer cells in immunity to cancer, and applications to immunotherapy. Nat Rev Immunol. 2023; 23(2):90-105.

[87]

Orange ST, et al. The exercise IL-6 enigma in cancer. Trends Endocrinol Metabol. 2023; 34(11):749-763.

[88]

Nash D, et al. IL-6 signaling in acute exercise and chronic training: Potential consequences for health and athletic performance. Scand J Med Sci Sports. 2023; 33(1):4-19.

[89]

Harvey KF, Zhang X, Thomas DM. The Hippo pathway and human cancer. Nat Rev Cancer. 2013; 13(4):246-257.

[90]

Lv L, Zhou X. Targeting Hippo signaling in cancer: novel perspectives and therapeutic potential. MedComm (2020). 2023; 4(5):e375.

[91]

WHO. Diabetes. WHO; 2024.

[92]

Katzmarzyk PT. Physical activity, sedentary behavior, and health: paradigm paralysis or paradigm shift? Diabetes. 2010; 59(11):2717-2725.

[93]

Thyfault JP, Bergouignan A. Exercise and metabolic health: beyond skeletal muscle. Diabetologia. 2020; 63(8):1464-1474.

[94]

McGee SL, Hargreaves M.Exercise performance and health: role of GLUT4. Free Radic Biol Med. 2024;224:479-483.

[95]

Chadt A, Al-Hasani H. Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease. Pflügers Archiv. 2020; 472(9):1273-1298.

[96]

Flores-Opazo M, McGee SL, Hargreaves M. Exercise and GLUT4. Exerc Sport Sci Rev. 2020; 48(3):110-118.

[97]

Fueger PT, et al. Glucose kinetics and exercise tolerance in mice lacking the GLUT 4 glucose transporter. J Physiol. 2007; 582(Pt 2):801-812.

[98]

Howlett KF, et al. Exercise-induced muscle glucose uptake in mice with graded, muscle-specific GLUT-4 deletion. Phys Rep. 2013; 1(3):e00065.

[99]

Zisman A, et al. Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat Med. 2000; 6(8): 924-928.

[100]

Richter EA, Hargreaves M. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev. 2013; 93(3):993-1017.

[101]

Ren JM, et al. Overexpression of Glut 4 protein in muscle increases basal and insulin-stimulated whole body glucose disposal in conscious mice. J Clin Investig. 1995; 95(1):429-432.

[102]

Richter EA, Sylow L, Hargreaves M. Interactions between insulin and exercise. Biochem J. 2021; 478(21):3827-3846.

[103]

Sylow L, et al. The many actions of insulin in skeletal muscle, the paramount tissue determining glycemia. Cell Metab. 2021; 33(4):758-780.

[104]

Meex RC, et al. Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity. Diabetes. 2010; 59(3): 572-579.

[105]

Sylow L, et al. Exercise-stimulated glucose uptake - regulation and implications for glycaemic control. Nat Rev Endocrinol. 2017; 13(3):133-148.

[106]

Frisbee JC. Reduced nitric oxide bioavailability contributes to skeletal muscle microvessel rarefaction in the metabolic syndrome. Am J Physiol Regul Integr Comp Physiol. 2005; 289(2):R307-R316.

[107]

Solomon TP, et al. Progressive hyperglycemia across the glucose tolerance continuum in older obese adults is related to skeletal muscle capillarization and nitric oxide bioavailability. J Clin Endocrinol Metab. 2011; 96(5):1377-1384.

[108]

Dreher SI, et al. Acute and long-term exercise adaptation of adipose tissue and skeletal muscle in humans: a matched transcriptomics approach after 8-week training-intervention. Int J Obes. 2023; 47(4):313-324.

[109]

Fisher G, et al. Effect of diet with and without exercise training on markers of inflammation and fat distribution in overweight women. Obesity. 2011; 19(6): 1131-1136.

[110]

Abel ED, et al. Adipose-selective targeting of the GLUT 4 gene impairs insulin action in muscle and liver. Nature. 2001; 409(6821):729-733.

[111]

Sinha MK, et al. Adipose tissue glucose transporters in NIDDM. Decreased levels of muscle/fat isoform. Diabetes. 1991; 40(4):472-477.

[112]

Ferrara CM, et al. Short-term exercise enhances insulin-stimulated GLUT-4 translocation and glucose transport in adipose cells. J Appl Physiol (1985). 1998; 85(6):2106-2111.

[113]

Hirshman MF, et al. Exercise training increases GLUT-4 protein in rat adipose cells. Am J Physiol. 1993; 264(6pt1):E882-9.

[114]

Stallknecht B, et al. Effect of physical training on glucose transporter protein and mRNA levels in rat adipocytes. Am J Physiol. 1993; 265(1pt1):E128-34.

[115]

Rodnick KJ, et al. Improved insulin action in muscle, liver, and adipose tissue in physically trained human subjects. Am J Physiol. 1987; 253(5pt1):E489-95.

[116]

Hussey SE, et al. Exercise training increases adipose tissue GLUT 4 expression in patients with type 2 diabetes. Diabetes Obes Metabol. 2011; 13(10):959-962.

[117]

Curran M, et al. The benefits of physical exercise for the health of the pancreatic beta-cell: a review of the evidence. Exp Physiol. 2020; 105(4):579-589.

[118]

2024 Alzheimer's disease facts and figures. Alzheimers Dement. 2024; 20(5): 3708-3821.

[119]

Patterson C.World Alzheimer's Report 2018. Alzheimer's Disease International; 2018.

[120]

Huuha AM, et al. Can exercise training teach us how to treat Alzheimer's disease? Ageing Res Rev. 2022;75:101559.

[121]

Imamura T, et al. Insulin deficiency promotes formation of toxic amyloid-beta 42 conformer co-aggregating with hyper-phosphorylated tau oligomer in an Alzheimer's disease model. Neurobiol Dis. 2020;137:104739.

[122]

Xu L, et al. Brain metabolism in Alzheimer's disease: biological mechanisms of exercise. Transl Neurodegener. 2023; 12(1):33.

[123]

Guo L, et al. Effect of exercise on cognitive function and synaptic plasticity in Alzheimer's disease models: a systematic review and meta-analysis. Front Aging Neurosci. 2022;14:1077732.

[124]

Liu HL, et al. Long-term treadmill exercise inhibits the progression of Alzheimer's disease-like neuropathology in the hippocampus of APP/PS1 transgenic mice. Behav Brain Res. 2013;256:261-272.

[125]

Valenzuela PL, et al. Exercise benefits on Alzheimer's disease: state-of-the-science. Ageing Res Rev. 2020;62:101108.

[126]

Lopez-Ortiz S, et al. Effects of physical activity and exercise interventions on Alzheimer's disease: an umbrella review of existing meta-analyses. J Neurol. 2023; 270(2):711-725.

[127]

Ionescu-Tucker A, Cotman CW. Emerging roles of oxidative stress in brain aging and Alzheimer's disease. Neurobiol Aging. 2021;107:86-95.

[128]

Intlekofer KA, Cotman CW. Exercise counteracts declining hippocampal function in aging and Alzheimer's disease. Neurobiol Dis. 2013;57:47-55.

[129]

Erickson KI, et al. Physical activity, cognition, and brain outcomes: a Review of the 2018 physical activity guidelines. Med Sci Sports Exerc. 2019; 51(6):1242-1251.

[130]

Blondell SJ, Hammersley-Mather R, Veerman JL. Does physical activity prevent cognitive decline and dementia?: a systematic review and meta-analysis of longitudinal studies. BMC Public Health. 2014;14:510.

[131]

Buchman AS, et al. Total daily physical activity and the risk of AD and cognitive decline in older adults. Neurology. 2012; 78(17):1323-1329.

[132]

Andrade A, et al. Effects of exercise in the treatment of Alzheimer's disease: an umbrella review of systematic reviews and meta-analyses. J Aging Phys Activ. 2022; 30(3):535-551.

[133]

Demurtas J, et al. Physical activity and exercise in mild cognitive impairment and dementia: an umbrella review of intervention and observational studies. J Am Med Dir Assoc. 2020; 21(10):1415-1422. e6.

[134]

Pedersen BK, et al. Searching for the exercise factor: is IL-6 a candidate? J Muscle Res Cell Motil. 2003; 24(2-3):113-119.

[135]

Severinsen MCK, Pedersen BK. Muscle-organ crosstalk: the emerging Roles of myokines. Endocr Rev. 2020; 41(4):594-609.

[136]

Safdar A, Saleem A, Tarnopolsky MA. The potential of endurance exercise-derived exosomes to treat metabolic diseases. Nat Rev Endocrinol. 2016; 12(9):504-517.

[137]

Chow LS, et al. Exerkines in health, resilience and disease. Nat Rev Endocrinol. 2022; 18(5):273-289.

[138]

Leuchtmann AB, et al. The role of the skeletal muscle secretome in mediating endurance and resistance training adaptations. Front Physiol. 2021;12:709807.

[139]

McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997; 387(6628):83-90.

[140]

Jang J, et al. Myostatin inhibition-induced Increase in muscle Mass and strength was Amplified by resistance exercise training, and dietary essential amino acids improved muscle Quality in mice. Nutrients. 2021; 13(5):1508.

[141]

Grobet L, et al. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nat Genet. 1997; 17(1):71-74.

[142]

Mosher DS, et al. A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genet. 2007; 3(5):e79.

[143]

Kanzleiter T, et al. The myokine decorin is regulated by contraction and involved in muscle hypertrophy. Biochem Biophys Res Commun. 2014; 450(2):1089-1094.

[144]

Miura T, et al. Decorin binds myostatin and modulates its activity to muscle cells. Biochem Biophys Res Commun. 2006; 340(2):675-680.

[145]

Saremi A, et al. Effects of oral creatine and resistance training on serum myostatin and GASP-1. Mol Cell Endocrinol. 2010; 317(1-2):25-30.

[146]

Hittel DS, et al. Myostatin decreases with aerobic exercise and associates with insulin resistance. Med Sci Sports Exerc. 2010; 42(11):2023-2029.

[147]

Broholm C, et al. Exercise induces expression of leukaemia inhibitory factor in human skeletal muscle. J Physiol. 2008; 586(8):2195-2201.

[148]

Gao S, et al. Acute myotube protein synthesis regulation by IL-6-related cytokines. Am J Physiol Cell Physiol. 2017; 313(5):C487-C500.

[149]

Serrano AL, et al. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab. 2008; 7(1):33-44.

[150]

Broholm C, Pedersen BK. Leukaemia inhibitory factor-an exercise-induced myokine. Exerc Immunol Rev. 2010;16:77-85.

[151]

Nielsen AR, et al. Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition. J Physiol. 2007; 584(Pt 1):305-312.

[152]

Haugen F, et al. IL-7 is expressed and secreted by human skeletal muscle cells. Am J Physiol Cell Physiol. 2010; 298(4):C807-C816.

[153]

Grabstein KH, et al. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science. 1994; 264(5161):965-968.

[154]

Busquets S, et al. Interleukin-15 decreases proteolysis in skeletal muscle: a direct effect. Int J Mol Med. 2005; 16(3):471-476.

[155]

Waldemer-Streyer RJ, Kim D, Chen J. Muscle cell-derived cytokines in skeletal muscle regeneration. FEBS J. 2022; 289(21):6463-6483.

[156]

Pedersen BK, Febbraio MA.Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008; 88(4):1379-1406.

[157]

Fischer CP. Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev. 2006;12:6-33.

[158]

Keller C, et al. Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle. J Appl Physiol (1985). 2005; 99(6):2075-2079.

[159]

Carey AL, et al. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes. 2006; 55(10):2688-2697.

[160]

Kahn BB, et al. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005; 1(1):15-25.

[161]

Matthews VB, et al. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia. 2009; 52(7):1409-1418.

[162]

Subbotina E, et al. Musclin is an activity-stimulated myokine that enhances physical endurance. Proc Natl Acad Sci U S A. 2015; 112(52):16042-16047.

[163]

Quindry JC, Franklin BA. Exercise preconditioning as a cardioprotective phenotype. Am J Cardiol. 2021;148:8-15.

[164]

Harris MP, et al. Myokine musclin is critical for exercise-induced cardiac conditioning. Int J Mol Sci. 2023; 24(7):6525.

[165]

Wang Z, et al. Irisin protects heart against ischemia-reperfusion injury through a SOD2-dependent mitochondria mechanism. J Cardiovasc Pharmacol. 2018; 72(6): 259-269.

[166]

Jandova T, et al. Long-term Effect of Exercise on irisin blood levels-systematic Review and meta-analysis. Health Care. 2021; 9(11):1438.

[167]

Albrecht E, et al. Irisin - a myth rather than an exercise-inducible myokine. Sci Rep. 2015;5:8889.

[168]

Jedrychowski MP, et al. Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell Metab. 2015; 22(4):734-740.

[169]

Bei Y, et al. Exercise-induced circulating extracellular vesicles protect against cardiac ischemia-reperfusion injury. Basic Res Cardiol. 2017; 112(4):38.

[170]

Gao L, et al. Skeletal muscle Nrf 2 Contributes to exercise-evoked systemic antioxidant defense via extracellular vesicular communication. Exerc Sport Sci Rev. 2021; 49(3):213-222.

[171]

Guo Y, Chen J, Qiu H. Novel mechanisms of exercise-induced cardioprotective factors in myocardial infarction. Front Physiol. 2020;11:199.

[172]

Lisi V, et al. Plasma-derived extracellular vesicles released after endurance exercise exert cardioprotective activity through the activation of antioxidant pathways. Redox Biol. 2023;63:102737.

[173]

Zhao H, et al. Small extracellular vesicles from Brown adipose tissue mediate exercise cardioprotection. Circ Res. 2022; 130(10):1490-1506.

[174]

Hou Z, et al. Longterm exercise-derived Exosomal miR-342-5p: a novel Exerkine for cardioprotection. Circ Res. 2019; 124(9):1386-1400.

[175]

Wang Y, Yang Y, Song Y. Cardioprotective effects of exercise: the role of irisin and exosome. Curr Vasc Pharmacol. 2024; 22(5):316-334.

[176]

Femmino S, et al. Extracellular vesicles and cardiovascular system: biomarkers and cardioprotective effectors. Vasc Pharmacol. 2020;135:106790.

[177]

Powers SK, Lategan-Potgieter R, Goldstein E. Exercise-induced Nrf2 activation increases antioxidant defenses in skeletal muscles. Free Radic Biol Med. 2024;224: 470-478.

[178]

Wrann CD. FNDC5/irisin - their role in the nervous system and as a mediator for beneficial effects of exercise on the brain. Brain Plast. 2015; 1(1):55-61.

[179]

Moon HY, et al. Running-induced systemic cathepsin B secretion is Associated with memory function. Cell Metab. 2016; 24(2):332-340.

[180]

Wrann CD, et al. Exercise induces hippocampal BDNF through a PGC-1alpha/FNDC 5 pathway. Cell Metab. 2013; 18(5):649-659.

[181]

De la Rosa A, et al. Long-term exercise training improves memory in middle-aged men and modulates peripheral levels of BDNF and Cathepsin B. Sci Rep. 2019; 9(1): 3337.

[182]

de Freitas GB, Lourenco MV, De Felice FG.Protective actions of exercise-related FNDC5/Irisin in memory and Alzheimer's disease. J Neurochem. 2020; 155(6): 602-611.

[183]

Lourenco MV, et al. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer's models. Nat Med. 2019; 25(1):165-175.

[184]

Esvald EE, et al. Differential regulation of the BDNF gene in cortical and hippocampal neurons. J Neurosci. 2022; 42(49):9110-9128.

AI Summary AI Mindmap
PDF (1038KB)

399

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/