Föreläsning Carl-Johan Sundberg
[email protected] 26 March 2015 Träning, gener & hälsa RF, Mars 2015 Carl Johan Sundberg Professor, leg läk Institutionen för Fysiologi & Farmakologi, Karolinska Institutet Ledamot Ordförande Ledamot Ledamot [email protected] Styrelsen för Centrum för Idrottsforskning Yrkesföreningar för Fysisk Aktivitet IOC Medical Commission WADA, gene doping panel 26 March 2015 [email protected] 26 March 2015 Se www.yfa.se [email protected] 26 March 2015 2015 1953: Morris’ bus personell studies Drivers: 90 % sitting time Conductors: 600 stairs/day Morris JN et al. Lancet, 1953 [email protected] 26 March 2015 Fysisk aktivitet har mycket stora och positiva effekter Akut & långsiktigt På välbefinnande/livskvalitet På kognition På fysisk kapacitet På fysisk hälsa/morbiditet På mortalitet [email protected] 26 March 2015 Sitting still breaks Avbrutet stillasittande sänker blodsocker och aktiverar gener Latouche C [email protected] 26 March 2015 [email protected] 26 March 2015 [email protected] 26 March 2015 Åkesson, JACC, 2014 [email protected] 26 March 2015 Löpning minskar risken att dö i förtid [email protected] 26 March 2015 Fysisk aktivitet ökar överlevnaden mer än ballongsprängning [email protected] 26 March 2015 Risken för diabetes lägre hos riskpatienter som är regelbundet fysiskt aktiva Lindström et al 2006 [email protected] 26 March 2015 Diabetes 2-3 år senare hos dem som är regelbundet fysiskt aktiva [email protected] 26 March 2015 Fysisk aktivitet minskar risken för cancer Idag finns epidemiologiska bevis för att regelbunden aktivitet ↓ risken för; Tjocktarmscancer (20-60%) Bröstcancer (20-50%) Prostatacancer Möjligen även lungcancer och livmodercancer Asian Pacific Journal of Cancer Prevention, vol14, 2013 [email protected] 26 March 2015 Physical activity with a cancer diagnosis Physical activity Improves QoL ↓ side effects of treatment ↓ Risk for relapse ↓ Mortality [email protected] 26 March 2015 Ahima & Lazar, Science 2013 [email protected] 26 March 2015 Strength/resistance training has marked health benefits [email protected] 26 March 2015 [email protected] 26 March 2015 [email protected] 26 March 2015 [email protected] 26 March 2015 Samband mellan motorisk förmåga och matematisk och språklig förmåga Haappalaa EA et al, MSSE 2014 [email protected] 26 March 2015 Betyg förbättras av program med fysisk aktivitet Käll LB et al, J School health, 2014 [email protected] 26 March 2015 [email protected] 26 March 2015 Åldrande & fysisk aktivitet • • • • • Den som motionerar lever längre Styrketräning kan öka muskelstyrka mycket Muskelmassa bibehålls bättre med träning Konditionen kan förbättras Aldrig för sent • Mitokondrier (”kraftstationer”) minskar i mängd med åldern – Träning ökar mängden – Genetisk modifierade möss som fick träna kunde återställa funktion & ”föryngrades” • Träning ökar förekomsten av kroppsegna antioxidanter • Telomererna längre hos dem som tränar [email protected] 26 March 2015 Elderly respond well Doubled strength in 2 months Frontera WR, J Appl Physiol 1988 [email protected] 26 March 2015 ADAPTATION TO REGULAR TRAINING [email protected] 26 March 2015 Effects on organ systems/tissues Heart Vasculature Blood Adipose tissue Connective tissue/bone/cartilage Inflammation markers & mechanisms Endocrine system Skeletal muscle ↑ mitochondrial density ↑ capillarization ↑ glucose transporters ↑ substrate storage ↓ fibre type IIb/x CNS/PNS [email protected] 26 March 2015 Complex – cardiovascular and other effects [email protected] Gielen S Circulation 2012 26 March 2015 [email protected] 26 March 2015 [email protected] 26 March 2015 Intervallträning • Historia • • • • • • OS 1912 Paavo Nurmi Fartlek Zatopek & Bannister Forskning 50- & 60-talen Duration • 30 s el 4 min – ej dagligen • Super-HIIT – 30 s på 250 % x 4-6 (~3 min) • ↑ Ox kap/mit • ↑ B-sockerkontroll – Tabata (20 + 10 s x 8 x 4/v) • Påverkar: – – – – – VO2-max Vikt/aptit Fettförbränning Cal-förbränning dygnet efter Blodtryck [email protected] 26 March 2015 [email protected] 26 March 2015 Maximal oxygen uptake [email protected] 26 March 2015 6 weeks, 3 sessions/wk: short duration can improve much Metcalfe RS Eur J Appl Physiol 2012 [email protected] 26 March 2015 Similar increase in energy expenditure after HIIT & continuous endurance exercise [email protected] 26 March 2015 Similar increase in energy expenditure after strength & endurance cycle exercise Melanson EL MSSE 2002 [email protected] 26 March 2015 Similar increase in flowmediated dilation in healthy humans after HIIT & continuous endurance exercise Rakobowchuk Am J Physiol Regul Integr Comp Physiol 2008 [email protected] 26 March 2015 The size of the training response Training status How often? How long? How hard? (frequency) (duration) (intensity) (Diet) (Age) Genes [email protected] 26 March 2015 Same but often different Training Results Same Different Different Same Same Different Same Different Not same outcome for different parameters Performance Vo2-max Strength Health related variables Metabolic control Blood pressure Mostly studied: aerobic (continuous vs HIIT) training, strength training – rarely in same individuals [email protected] 26 March 2015 [email protected] 26 March 2015 ”Endurance responders” ”Strength responders” Combined strength & endurance (2 + 2 sessions/week N=57, 40-67 yrs old People respond differently to same training Karavirta et al., MSSE, 2011 [email protected] 26 March 2015 Substantial genetic influence: homozygous twins respond similarly within the pair [email protected] Claude Bouchard26 March 1991 2015 High-responders Median responder Low-responders Rankinen 2001 [email protected] 26 March 2015 [email protected] 26 March 2015 Common with no or adverse response to regular exercise training? Bouchard C Plos One 2012 [email protected] 26 March 2015 Physical activity reduces blood pressure most in people with advantagegous genes Montasser ME, Am J Hypertens, 2011 [email protected] 26 March 2015 Examples of >200 studied performance enhancing polymorphisms (PEPs) Strength/power ACE ACTN3 Myostatin Anaerobic performance AMPd Endurance ACE Mitochondrial biogenesis PPAR/PGC-1 NRF-1 Oxygen transport/vascluarization VEGF HIF1 EPOR [email protected] 26 March 2015 [email protected] 26 March 2015 [email protected] 26 March 2015 Example mechanisms ↑ mitochondrial density in skeletal & heart muscle ↑ glucose transporters (GLUT-4) in skeletal muscle ↑ NOS formation in endothelial cells ↓ thrombosis ↑ vasodilation ↓ stress hormone (adrenaline, cortisol etc) levels ↓ systemic inflammation (CRP, fibrinogen) ↑ mineral and collagen in bone ↑ muscle control and balance around joints ↑ pain tolerance and higher pain threshold ↑ neurogenesis & other events in CNS ↑ aerobic/cardiorespiratory fitness ↑ telomere length [email protected] 26 March 2015 Perry CG J Physiol 2010 [email protected] 26 March 2015 HIF-1 regulation Ub Ub Ub -OH VHL Proteasome Normoxia HIF HIF ARNT Target gene Hypoxia [email protected] Rundqvist, H 2008 26 March 2015 Adaptation Celltillväxt & överlevnad IGF2 IGFBP BNIP-3 TGFβ Metabolism Nya blodkärl Syrgastransport PFK VEGF LDH VEGFR1 EPO GLUT1 Endothelin-1 HO-1 PDK-1 VEGFR2 Transferrin PGK Leptin iNOS Hif-1 Signaler i cellerna Hypoxi Hormoner Calcium Stimuli Tillväxtfaktorer Metabolism Fysisk aktivitet [email protected] Redox potential H Rundqvist 2008 26 March 2015 Specifika signaler ”talar om” för vävnaderna att de skall anpassa sig J Norrbom 2008 [email protected] 26 March 2015 [email protected] 26 March 2015 Handschin & Spiegelmann, Nature, 2008 [email protected] 26 March 2015 Stem cells & exercise Fiuza-Luces, F. Physiology, 2013 [email protected] 26 March 2015 Reactive oxygen species [email protected] 26 March 2015 [email protected] 26 March 2015 Genaktivitet & epigenetik påverkas på ett koordinerat sätt Lindholm M et al 2014 [email protected] 26 March 2015 Provläs: http://media.bonnierforlagen.se/bladd [email protected] erex/?isbn=9789173630580 26 March 2015 PhD Students Eva-karin Gidlund Malene Lindholm Mia Ydfors Dr Jessica Norrbom Dr Helene Rundqvist Assoc prof Helene Fischer Assoc prof Ingeborg van der Ploeg Dr Amarjit Saini Med Lic Susanna Appel M Sc Charlotte Schönbeck Molecular Exercise Physiology group [email protected] [email protected] 26 March 2015 [email protected] 26 March 2015
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