Editing Exercise (section)

== Mechanism of effects ==

=== Skeletal muscle ===
{{main|Skeletal muscle}}
Resistance training and subsequent consumption of a protein-rich meal promotes [[muscle hypertrophy]] and gains in [[muscle strength]] by stimulating [[myofibrillar]] muscle protein synthesis (MPS) and inhibiting muscle protein breakdown (MPB).<ref name="Skeletal muscle homeostasis 2016 review" /><ref name="Muscle hypertrophy review">{{cite journal | vauthors = Phillips SM | title = A brief review of critical processes in exercise-induced muscular hypertrophy | journal = Sports Medicine | volume = 44 | issue = Suppl 1 | pages = S71–S77 | date = May 2014 | pmid = 24791918 | pmc = 4008813 | doi = 10.1007/s40279-014-0152-3 }}</ref> The stimulation of muscle protein synthesis by resistance training occurs via [[phosphorylation]] of the [[mechanistic target of rapamycin]] (mTOR) and subsequent activation of [[mTORC1]], which leads to [[protein biosynthesis]] in cellular [[ribosome]]s via phosphorylation of mTORC1's immediate targets (the [[p70S6 kinase]] and the [[protein translation|translation]] repressor protein [[4EBP1]]).<ref name="Skeletal muscle homeostasis 2016 review" /><ref name="Molecular Aspects of Medicine 2016 review">{{cite journal | vauthors = Brioche T, Pagano AF, Py G, Chopard A | title = Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention | journal = Molecular Aspects of Medicine | volume = 50 | pages = 56–87 | date = August 2016 | pmid = 27106402 | doi = 10.1016/j.mam.2016.04.006 | s2cid = 29717535 | url = https://hal.archives-ouvertes.fr/hal-01837630/file/2016_Brioche_MAM_1.pdf }}</ref> The suppression of muscle protein breakdown following food consumption occurs primarily via increases in [[blood plasma|plasma]] [[insulin]].<ref name="Skeletal muscle homeostasis 2016 review" /><ref name="HMB in vivo human pharmacodynamics" /><ref name="Pharmacodynamics and pharmacokinetics of HMB-CA in humans in vivo" /> Similarly, increased muscle protein synthesis (via activation of mTORC1) and suppressed muscle protein breakdown (via insulin-independent mechanisms) has also been shown to occur following ingestion of [[β-hydroxy β-methylbutyric acid]].<ref name="Skeletal muscle homeostasis 2016 review" /><ref name="HMB in vivo human pharmacodynamics">{{cite journal | vauthors = Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, Loughna P, Churchward-Venne TA, Breen L, Phillips SM, Etheridge T, Rathmacher JA, Smith K, Szewczyk NJ, Atherton PJ | display-authors = 3 | title = Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism | journal = The Journal of Physiology | volume = 591 | issue = 11 | pages = 2911–2923 | date = June 2013 | pmid = 23551944 | pmc = 3690694 | doi = 10.1113/jphysiol.2013.253203 }}</ref><ref name="Pharmacodynamics and pharmacokinetics of HMB-CA in humans in vivo">{{cite journal | vauthors = Wilkinson DJ, Hossain T, Limb MC, Phillips BE, Lund J, Williams JP, Brook MS, Cegielski J, Philp A, Ashcroft S, Rathmacher JA, Szewczyk NJ, Smith K, Atherton PJ | display-authors = 3 | title = Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism | journal = Clinical Nutrition | volume = 37 | issue = 6 Pt A | pages = 2068–2075 | date = December 2018 | pmid = 29097038 | pmc = 6295980 | doi = 10.1016/j.clnu.2017.09.024 | quote =}}</ref><ref name="Sarcopenia July 2015 review">{{cite journal | vauthors = Phillips SM | title = Nutritional supplements in support of resistance exercise to counter age-related sarcopenia | journal = Advances in Nutrition | volume = 6 | issue = 4 | pages = 452–460 | date = July 2015 | pmid = 26178029 | pmc = 4496741 | doi = 10.3945/an.115.008367 }}</ref>

Aerobic exercise induces [[mitochondrial biogenesis]] and an increased capacity for [[oxidative phosphorylation]] in the [[mitochondria]] of skeletal muscle, which is one mechanism by which aerobic exercise enhances submaximal endurance performance.<ref>{{cite journal | vauthors = Wibom R, Hultman E, Johansson M, Matherei K, Constantin-Teodosiu D, Schantz PG | title = Adaptation of mitochondrial ATP production in human skeletal muscle to endurance training and detraining | journal = Journal of Applied Physiology | volume = 73 | issue = 5 | pages = 2004–2010 | date = November 1992 | pmid = 1474078 | doi = 10.1152/jappl.1992.73.5.2004 | url = http://urn.kb.se/resolve?urn=urn:nbn:se:gih:diva-184 }}</ref><ref name="Skeletal muscle homeostasis 2016 review" /><ref name="Aerobic exercise – mitochondrial biogenesis and OXPHOS capacity" /> These effects occur via an exercise-induced increase in the intracellular [[adenosine monophosphate|AMP]]:[[adenosine triphosphate|ATP]] ratio, thereby triggering the activation of [[AMP-activated protein kinase]] (AMPK) which subsequently phosphorylates [[PGC-1α|peroxisome proliferator-activated receptor gamma coactivator-1α]] (PGC-1α), the [[master regulator]] of mitochondrial biogenesis.<ref name="Skeletal muscle homeostasis 2016 review" /><ref name="Aerobic exercise – mitochondrial biogenesis and OXPHOS capacity">{{cite journal | vauthors = Boushel R, Lundby C, Qvortrup K, Sahlin K | title = Mitochondrial plasticity with exercise training and extreme environments | journal = Exercise and Sport Sciences Reviews | volume = 42 | issue = 4 | pages = 169–174 | date = October 2014 | pmid = 25062000 | doi = 10.1249/JES.0000000000000025 | s2cid = 39267910 | doi-access = free }}</ref><ref name="Mitochondrial biogenesis">{{cite journal | vauthors = Valero T | title = Mitochondrial biogenesis: pharmacological approaches | journal = Current Pharmaceutical Design | volume = 20 | issue = 35 | pages = 5507–5509 |year = 2014 | pmid = 24606795 | doi = 10.2174/138161282035140911142118 | hdl-access = free | hdl = 10454/13341 }}</ref>
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 | image1 = Muscle protein synthesis signaling cascades.jpg
 | alt1 = Signaling cascade diagram
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 | caption1 = Diagram of the molecular [[signaling cascade]]s that are involved in [[myofibrillar]] muscle protein synthesis and [[mitochondrial biogenesis]] in response to physical exercise and specific [[amino acid]]s or their derivatives (primarily [[leucine|{{nowrap|{{smallcaps all|L}}-leucine}}]] and [[Beta-Hydroxy beta-methylbutyric acid|HMB]]).<ref name="Skeletal muscle homeostasis 2016 review">{{cite journal | vauthors = Brook MS, Wilkinson DJ, Phillips BE, Perez-Schindler J, Philp A, Smith K, Atherton PJ | title = Skeletal muscle homeostasis and plasticity in youth and ageing: impact of nutrition and exercise | journal = Acta Physiologica | volume = 216 | issue = 1 | pages = 15–41 | date = January 2016 | pmid = 26010896 | pmc = 4843955 | doi = 10.1111/apha.12532 }}</ref> Many amino acids derived from food protein promote the activation of [[mTORC1]] and increase [[protein translation|protein synthesis]] by [[signal transduction|signaling]] through [[Rag GTPase]]s.<ref name="Skeletal muscle homeostasis 2016 review" /><ref name="The neurology of mTOR">{{cite journal | vauthors = Lipton JO, Sahin M | title = The neurology of mTOR | journal = Neuron | volume = 84 | issue = 2 | pages = 275–291 | date = October 2014 | pmid = 25374355 | pmc = 4223653 | doi = 10.1016/j.neuron.2014.09.034 }}<br />[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223653/figure/F2/ Figure 2: The mTOR Signaling Pathway]</ref><br />{{hidden|Abbreviations and representations|{{bull}}PLD: [[phospholipase D]]<br />{{bull}}PA: [[phosphatidic acid]]<br />{{bull}}mTOR: [[mechanistic target of rapamycin]]<br />{{bull}}AMP: [[adenosine monophosphate]]<br />{{bull}}ATP: [[adenosine triphosphate]]<br />{{bull}}AMPK: [[AMP-activated protein kinase]]<br />{{bull}}PGC-1α: [[PGC-1α|peroxisome proliferator-activated receptor gamma coactivator-1α]]<br />{{bull}}S6K1: [[p70S6 kinase]]<br />{{bull}}4EBP1: [[EIF4EBP1|eukaryotic translation initiation factor 4E-binding protein 1]]<br />{{bull}}eIF4E: [[eukaryotic translation initiation factor 4E]]<br />{{bull}}RPS6: [[ribosomal protein S6]]<br />{{bull}}eEF2: [[eukaryotic elongation factor 2]]<br />{{bull}}RE: resistance exercise; EE: endurance exercise<br />{{bull}}Myo: [[myofibrillar]]; Mito: [[mitochondria]]l<br />{{bull}}AA: [[amino acid]]s<br />{{bull}}HMB: [[β-hydroxy β-methylbutyric acid]]<br />{{bull}}↑ represents activation<br />{{bull}}Τ represents inhibition | headerstyle=background:#ccccff | style=text-align:center; }}
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 | image2 = Resistance exercise-induced muscle protein synthesis.jpg
 | alt2 = Graph of muscle protein synthesis vs time
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 | caption2 = Resistance training stimulates muscle protein synthesis (MPS) for a period of up to 48&nbsp;hours following exercise (shown by dotted line).<ref name="Muscle hypertrophy review" /> Ingestion of a protein-rich meal at any point during this period will augment the exercise-induced increase in muscle protein synthesis (shown by solid lines).<ref name="Muscle hypertrophy review" />
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=== Other peripheral organs ===
[[File:Aerobic Anaerobic Exercise Adaptations.jpg|400px|thumb|Summary of long-term adaptations to regular aerobic and anaerobic exercise. Aerobic exercise can cause several central cardiovascular adaptations, including an increase in [[stroke volume]] (SV)<ref name=Exercise_SV>{{cite journal | vauthors = Wang E, Næss MS, Hoff J, Albert TL, Pham Q, Richardson RS, Helgerud J | title = Exercise-training-induced changes in metabolic capacity with age: the role of central cardiovascular plasticity | journal = Age | volume = 36 | issue = 2 | pages = 665–676 | date = April 2014 | pmid = 24243396 | pmc = 4039249 | doi = 10.1007/s11357-013-9596-x }}</ref> and maximal aerobic capacity ([[VO2 max|VO<sub>2</sub> max]]),<ref name=Exercise_SV /><ref name=AerobicMotorCapability>{{cite journal | vauthors = Potempa K, Lopez M, Braun LT, Szidon JP, Fogg L, Tincknell T | title = Physiological outcomes of aerobic exercise training in hemiparetic stroke patients | journal = Stroke | volume = 26 | issue = 1 | pages = 101–105 | date = January 1995 | pmid = 7839377 | doi = 10.1161/01.str.26.1.101 }}</ref> as well as a decrease in [[resting heart rate]] (RHR).<ref name=Exercise_RHR1>{{cite journal | vauthors = Wilmore JH, Stanforth PR, Gagnon J, Leon AS, Rao DC, Skinner JS, Bouchard C | title = Endurance exercise training has a minimal effect on resting heart rate: the Heritage Study | journal = Medicine and Science in Sports and Exercise | volume = 28 | issue = 7 | pages = 829–835 | date = July 1996 | pmid = 8832536 | doi = 10.1097/00005768-199607000-00009 | doi-access = free }}</ref><ref name=Exercise_RHR2>{{cite journal | vauthors = Carter JB, Banister EW, Blaber AP | title = Effect of endurance exercise on autonomic control of heart rate | journal = Sports Medicine | volume = 33 | issue = 1 | pages = 33–46 | year = 2003 | pmid = 12477376 | doi = 10.2165/00007256-200333010-00003 | s2cid = 40393053 }}</ref><ref name=Exercise_RHR3>{{cite journal| vauthors = Chen CY, Dicarlo SE |title=Endurance exercise training-induced resting Bradycardia: A brief review|journal=Sports Medicine, Training and Rehabilitation|date=January 1998|volume=8|issue=1|pages=37–77|doi=10.1080/15438629709512518}}</ref> Long-term adaptations to resistance training, the most common form of anaerobic exercise, include [[muscular hypertrophy]],<ref name=Exercise_Hypertrophy>{{cite journal | vauthors = Crewther BT, Heke TL, Keogh JW | title = The effects of a resistance-training program on strength, body composition and baseline hormones in male athletes training concurrently for rugby union 7's | journal = The Journal of Sports Medicine and Physical Fitness | volume = 53 | issue = 1 | pages = 34–41 | date = February 2013 | pmid = 23470909 }}</ref><ref name=Exercise_Hypertrophy2>{{cite journal | vauthors = Schoenfeld BJ | title = Postexercise hypertrophic adaptations: a reexamination of the hormone hypothesis and its applicability to resistance training program design | journal = Journal of Strength and Conditioning Research | volume = 27 | issue = 6 | pages = 1720–1730 | date = June 2013 | pmid = 23442269 | doi = 10.1519/JSC.0b013e31828ddd53 | s2cid = 25068522 | doi-access = free }}</ref> an increase in the [[physiological cross-sectional area]] (PCSA) of muscle(s), and an increase in [[neural drive]],<ref name=Exercise_Neuraldrive>{{cite journal | vauthors = Dalgas U, Stenager E, Lund C, Rasmussen C, Petersen T, Sørensen H, Ingemann-Hansen T, Overgaard K | display-authors = 6 | title = Neural drive increases following resistance training in patients with multiple sclerosis | journal = Journal of Neurology | volume = 260 | issue = 7 | pages = 1822–1832 | date = July 2013 | pmid = 23483214 | doi = 10.1007/s00415-013-6884-4 | s2cid = 848583 }}</ref><ref name=AnaerobicStrength>{{cite journal | vauthors = Staron RS, Karapondo DL, Kraemer WJ, Fry AC, Gordon SE, Falkel JE, Hagerman FC, Hikida RS | display-authors = 3 | title = Skeletal muscle adaptations during early phase of heavy-resistance training in men and women | journal = Journal of Applied Physiology | volume = 76 | issue = 3 | pages = 1247–1255 | date = March 1994 | pmid = 8005869 | doi = 10.1152/jappl.1994.76.3.1247 | s2cid = 24328546 }}</ref> both of which lead to increased [[muscular strength]].<ref name=Exercise_MuscularStrength>{{cite journal | vauthors = Folland JP, Williams AG | title = The adaptations to strength training : morphological and neurological contributions to increased strength | journal = Sports Medicine | volume = 37 | issue = 2 | pages = 145–168 | year = 2007 | pmid = 17241104 | doi = 10.2165/00007256-200737020-00004 | s2cid = 9070800 }}</ref> Neural adaptations begin more quickly and plateau prior to the hypertrophic response.<ref name=NeuralvsHypertrophy1>{{cite journal | vauthors = Moritani T, deVries HA | title = Neural factors versus hypertrophy in the time course of muscle strength gain | journal = American Journal of Physical Medicine | volume = 58 | issue = 3 | pages = 115–130 | date = June 1979 | pmid = 453338 }}</ref><ref name=NeuralvsHypertrophy2>{{cite journal | vauthors = Narici MV, Roi GS, Landoni L, Minetti AE, Cerretelli P | title = Changes in force, cross-sectional area and neural activation during strength training and detraining of the human quadriceps | journal = European Journal of Applied Physiology and Occupational Physiology | volume = 59 | issue = 4 | pages = 310–319 | year = 1989 | pmid = 2583179 | doi = 10.1007/bf02388334 | s2cid = 2231992 }}</ref>]]
Developing research has demonstrated that many of the benefits of exercise are mediated through the role of skeletal muscle as an endocrine organ. That is, contracting muscles release multiple substances known as [[myokine]]s which promote the growth of new tissue, tissue repair, and multiple anti-inflammatory functions, which in turn reduce the risk of developing various inflammatory diseases.<ref>{{cite journal | vauthors = Pedersen BK | title = Muscle as a secretory organ | journal = Comprehensive Physiology | volume = 3 | issue = 3 | pages = 1337–1362 | date = July 2013 | pmid = 23897689 | doi = 10.1002/cphy.c120033 | isbn = 978-0-470-65071-4 }}</ref> Exercise reduces levels of [[cortisol]], which causes many health problems, both physical and mental.<ref>{{cite journal | vauthors = Cohen S, Williamson GM | title = Stress and infectious disease in humans | journal = Psychological Bulletin | volume = 109 | issue = 1 | pages = 5–24 | date = January 1991 | pmid = 2006229 | doi = 10.1037/0033-2909.109.1.5 }}</ref> Endurance exercise before meals lowers [[Blood sugar level|blood glucose]] more than the same exercise after meals.<ref>{{cite journal | vauthors = Borer KT, Wuorinen EC, Lukos JR, Denver JW, Porges SW, Burant CF | title = Two bouts of exercise before meals, but not after meals, lower fasting blood glucose | journal = Medicine and Science in Sports and Exercise | volume = 41 | issue = 8 | pages = 1606–1614 | date = August 2009 | pmid = 19568199 | doi = 10.1249/MSS.0b013e31819dfe14 | s2cid = 207184758 | doi-access = free }}</ref> There is evidence that vigorous exercise (90–95% of [[VO2 max|VO<sub>2</sub> max]]) induces a greater degree of physiological [[cardiac hypertrophy]] than moderate exercise (40 to 70% of VO<sub>2</sub> max), but it is unknown whether this has any effects on overall morbidity and/or mortality.<ref>{{cite journal | vauthors = Wisløff U, Ellingsen Ø, Kemi OJ | title = High-intensity interval training to maximize cardiac benefits of exercise training? | journal = Exercise and Sport Sciences Reviews | volume = 37 | issue = 3 | pages = 139–146 | date = July 2009 | pmid = 19550205 | doi = 10.1097/JES.0b013e3181aa65fc | s2cid = 25057561 | doi-access = free }}</ref> Both aerobic and anaerobic exercise work to increase the mechanical efficiency of the heart by increasing cardiac volume (aerobic exercise), or myocardial thickness (strength training). [[Ventricular hypertrophy]], the thickening of the ventricular walls, is generally beneficial and healthy if it occurs in response to exercise.

=== Central nervous system ===
{{Further|Neurobiological effects of physical exercise#Neuroplasticity}}
The effects of physical exercise on the [[central nervous system]] may be mediated in part by specific [[neurotrophic factor]] [[myokine|hormones released into the blood by muscles]], including [[brain-derived neurotrophic factor|BDNF]], [[insulin-like growth factor 1|IGF-1]], and [[vascular endothelial growth factor|VEGF]].<ref name="Exercise – neurotrophic factors + basal ganglia">{{cite journal | vauthors = Paillard T, Rolland Y, de Souto Barreto P | title = Protective Effects of Physical Exercise in Alzheimer's Disease and Parkinson's Disease: A Narrative Review | journal = Journal of Clinical Neurology | volume = 11 | issue = 3 | pages = 212–219 | date = July 2015 | pmid = 26174783 | pmc = 4507374 | doi = 10.3988/jcn.2015.11.3.212 | quote = }}</ref><ref name="BDNF meta analysis">{{cite journal | vauthors = Szuhany KL, Bugatti M, Otto MW | title = A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor | journal = Journal of Psychiatric Research | volume = 60 | pages = 56–64 | date = January 2015 | pmid = 25455510 | pmc = 4314337 | doi = 10.1016/j.jpsychires.2014.10.003 | quote =}}</ref><ref name="Cerebral hemodynamics and AD">{{cite journal | vauthors = Tarumi T, Zhang R | title = Cerebral hemodynamics of the aging brain: risk of Alzheimer disease and benefit of aerobic exercise | journal = Frontiers in Physiology | volume = 5 | pages = 6 | date = January 2014 | pmid = 24478719 | pmc = 3896879 | doi = 10.3389/fphys.2014.00006 | quote = | doi-access = free }}</ref>