Marco Narici School of Graduate Entry to Medicine and Health, MRC ARUK Centre for Musculoskeletal Ageing Research University of Nottingham United

Transcription

1 Marco Narici School of Graduate Entry to Medicine and Health, MRC ARUK Centre for Musculoskeletal Ageing Research University of Nottingham United Kingdom

2 Pathophysiological effects of spaceflight

3 Muscle loss in space: an unresolved problem Since Yuri Gagarin s flight in 1961, more than 540 human beings have flown into space At present, full prevention of muscle loss in space has yet to be achieved

4 Muscle atrophy after spaceflight 17-day Shuttle mission #$ % month MIR mission #$ % &$ %!#$ % ( ) &% ( ) "% *+,%-. /% 01 % 23 4% &$ %!#$ % ( ) &% ( ) "!*% +, -%./0% 12 % 34 5%!' &$ % 5 678%!' &$ % 6 789%!' #$ % 971 % : 7; <%!' #$ % : 82 % ; 8<=%!"&$ % =23 72%!"&$ % >34 83%!"#$ %!"#$ % LeBlanc et al J Appl Physiol 89: , 2000

5 Launch: 21 December 2011 Vector: Soyuz TMA-03M flight Landing: 1 July 2012 Duration: 193 days Sarcolab testing dates: Pre-flight: 3 rd OCT 2011 Post-flight 1: 2 nd JULY 2012 Post-flight 2: 17 th JULY 2012

6 MRI Before Flight After Flight

7 % change Triceps surae volume Gastroc. medialis Gastroc. lateralis Soleus Days (-BDC1)

8 CSA SINGLE MUSCLE FIBERS ctrl astronaut pre flight astronaut post flight The analysis of the astronaut CSA shows: Significant difference between our ctrl (pre ULLS) and the fibers of the astronaut pre-flight Significant difference between the fibers post-flight and pre-flight. no significant difference between our controls and post-flight. 45% decrease from pre-flight to post-flight

9 SPECIFIC FORCE OF SINGLE MUSCLE FIBERS ctrl type 1 fiber astro pre flight astro post flight Significant difference between our control and astronaut pre flight(-15%). Significant difference pre and post flight (-23%).

10 Muscle Proteome R+ 0 R+ 16 spots changed: 195 spots changed: spots changed at R+0 were not normalized at R spots changed at R+0 were normalized at R spots were changed only at R+16

11 Exercises performed by ISS crew 23 h of RT, 120 hr of aerobic exercise, giving a total of 20,800 muscle RT contractions, 159,000 concentric cyclic contractions, and 281,000 treadmill steps (Trappe et al., J Appl Physiol 106: , 2009).

12 Pathways controlling muscle mass Sandri (2003) Physiology, 23,

13 Galactic cosmic radiation risks Average effective dose for a 6 month stay on the ISS ~72 msv (based on current ISS wall shielding of 20 g/cm 2 ) The NSCR-2012 model* predicts the upper 95% CL for space radiation risk for ISS missions near solar minimum could exceed the NASA REID limit for cancer fatality by 18 months for females and 24 months for males (Cucinotta, PlosOne, 9, 2014). i.e. female would exceed their maximum acceptable dose of radiation in 18 months and men in 24 months of spaceflight. Increased risks involve DNA damage, cell membrane damage, damage to CV, nervous and lymphatic systems, stem cells (?). Acute effects: inflammation and oxidative stress, likely contributing to muscle wasting. Repeated ISS missions or missions to Mars are a concern. * NASA cancer risk assessment model

14 Deconditioning of the musculoskeletal system in simulated microgravity: effects of 90-day bed rest -6 deg

15 Resistive countermeasures Monitor Goniometer Flywheels Courtesy of Prof. Per Tesch, Mid-Sweden University, Sweden

16 Time course of muscle atrophy: lessons form bed rest studies LTBR Toulouse ` LTBR Toulouse Mortality risk

17 Muscle Architecture and Tendon Measurements Superficial aponeurosis Deep aponeurosis plantaris GM GL 10 mm GM Fascicle Pennation angle External marker gastroc. tendon Achilles tendon Myo-tendinous junction 10 mm

18 Fascicle length (mm) Pennation angle (deg) Muscle architecture Significant alterations in muscle architecture found after 90 days of head-down bed rest 50 Exercise Grp. Control Grp * -7% -10% ** -13% -13% Pre bed rest Post bed rest 10 Pre bed rest Post bed rest

19 Investigation into the mechanisms of muscle loss during simulated microgravity Valdoltra BR study 2007

20 Mechano-transduction in skeletal muscle M. Flück et al. J. Exp. Biol. 205, (2002)

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22 Tendon Mechanical Properties

23 Effect of bed rest on young and older men Valdoltra Bed Rest Facility, Koper, Slovenia

24 The 2013 Valdoltra Bed Test

25 Effect of BR on muscle mass, strength and power

26 Effect of BR on maximum aerobic capacity and gait speed

27 Effect of BR on fat mass and insulin sensitivity

28 Impact of inactivity and overfeeding on insulin sensitivity Knudsen et al J Appl Physiol (2012); 113: 7-15.

29 Overfeeding with inactivity leads to increased fat deposition, activating systemic inflammation, accelerating disuse-atrophy

30 Inactivity (60-d BR) leads to neuromuscular degeneration Salanova et al. FASEB, 25, 2011

31 CONCLUSIONS Loss of muscle mass is an inevitable consequence of spaceflight. This is associated with a deterioration of neuromuscular function and with an increased risk of insulin resistance. Bed rest is an extremely useful simulated microgravity model for studying the mechanisms of disuse muscle atrophy, not compounded by disease. Up to 2008, the loading intensity and volume of resistive training used on the ISS seemed insufficient for a full prevention of muscle loss in space. The stimuli for muscle atrophy seem much greater than those on Earth. Although the new NASA Advanced Resistive Exercise Device (ARED) seems promising, a combined approach based on exercise, nutritional and pharmacological interventions may be useful. The risks posed by galactic cosmic radiation for repeated ISS missions, or ISS missions >1 year or exploration missions to Mars and other deep space destinations, are a concern. Systematic dosimetry data collection is needed.

32 Acknowledgements Prof. Paolo Cerretelli: University of Milan, Italy Prof. Roberto Bottinelli: University of Pavia, Italy Prof. Cecilia Gelfi: University of Milan, Italy Prof. Rado Pisot: University of Primorska, Koper, Slovenia Dr Bostjan Simunic: University of Primorska, Koper, Slovenia Prof. J Rittweger: German Space Agency (DLR), Koeln, Germany Prof. Martin Flück: ETH, Zurich, CH Prof. C Franceschi: University of Bologna, Italy Dr M Capri: University of Bologna, Italy Prof. S Salvioli: University of Bologna, Italy Prof. O Seynnes: University of Oslo, NO Dr Irene di Giulio: University College London, UK European Space Agency Slovenian Ministry of Defence Italian Space Agency