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  • Lady and gentleman, thank you to invite me
  • During my presentation I will try to convince you how much physical activity is important to prevent the loss of muscle mass and to prevent the falls. I will discuss sarcopenia has a risk factor for falls The deleterious consequences of inactivity We will speak about Resistance training why is currently the best way to prevent sarcopenia. Why and how do we build muscle when exercising
  • Why and how do we build muscle when exercising
  • You are probably familiar to this picture. Between the age of 30 and 80 we lose about 30% of our muscle mass. The slope is stepper after 60-70 y old We all know for years that people involve in PA have a higher amount of muscle mass and strength.
  • At the individual level the story is probably a little different with period of acute loss of muscle mass. The slope of decline and recovery can be very different between the subject and ages and one of the reason is Physical activity
  • As a geriatrician, the aim of PA is the reduce the consequences of this muscle mass decline in elderly subjects.
  • But the same can said all the lifelong because we know that poor muscle mass in aldult is also associated in bad outcomes such as fonctional decline or falls in the older people.
  • Why and how do we build muscle when exercising
  • Sarcopenia is not a single disease with a linear process but a geriatric syndrom, and several factors create a cascade with a negative spiral eventually leading to disability, dependence and death. loops
  • The two main causes of the high incidence of fracture are the prevalence of OP and the incidence of falls. falls are a significant problem for older adults and that treatment and complications result in high healthcare costs. To prevent falls through the development of effective screening, prevention, and rehabilitation programs, it is important to identify modifiable risk factors for falling.
  • In elderly people, the risk of fall result from the combinaison of both low BMD and an increase number of falls. If we want to prevent the number of fracture we have got to treat OP but also to prevent the number of falls.
  • Indeed it has been repeteadly reported that difficilties to perform tasks such as …, inactivity, and poor physical performances are strong risk factors for fractures.
  • In a meta-analysis performed in 2004, it was reported that people with Lower extremity weakness had a 1. increase risk of any fall and a 3 increase risk of recurrents falls.
  • However it also be reported that “Although muscle weakness appears to be an independent risk factor for falls, there is not strong evidence supporting strength training in preventive programs.” Most studies used some combination of resistance exercises, balance exercises, endurance exercises, and flexibility, but only three of these studies59–61 isolated resisted muscle strength training as the independent variable.
  • Most intervention program that have been assess are multifactorial with (balance training, endurance training..) program but if you look the independent impact of each item there no statistical evidences that strength prevent falls.
  • One of the reason is that if you have to fight again the risk of fall you have to reduce coimpairment wich are much more at risk of falls that just one impirment.
  • Why and how do we build muscle when exercising
  • Sarcopenia is a geriatric syndrom with multiple risk factors. Amongst these risk factor disuse and inactivity is one of the man risk factor. Elderly poeple are especially exposed to this risk factor.
  • Rappel des définitions de la force musculaire et de l'endurance. Les déterminants physiologiques et biochimiques vont très largement différer.
  • Rappel des définitions de la force musculaire et de l'endurance. Les déterminants physiologiques et biochimiques vont très largement différer.
  • Why and how do we build muscle when exercising
  • When we try to summ up the effet of physical activity, we can say that there the endurance training and the resisitance training
  • He is a lauwer and he swear in his book that he never took any hormons.
  • 25 poeple in each group Leg extension and flexion The total volume of exercise was identicale. The curve Past 60 % is flat and so the is no benefit to train over 60-70 %
  • Robust evidence in several studies indicate that resistance training such as weight lifting increases myofibrillar muscle protein synthesis
  • Several reports suggest that maintaining the benefits from resistance training is possible with as little as one exercise program per week
  • Increase in muscle mass is explain twice (X2) by hypertrophy than hyperplasia Meta analyse realisée chez l’animal
  • contrindication
  • But of cause this can be challenging in older poeple
  • Why and how do we build muscle when exercising
  • Physical activity Actually, no pharmacological or behavioral intervention has proven to be as efficacious as resistance training to reverse sarcopenia. The American College of Sport Medicine and the American Heart Association suggested that training at a 70-90% of 1-RM (maximal repetition) on two or more nonconsecutive days per week was the appropriate training intensity to produce gains in muscle size and strength, even in frail elderly [115, 216]. One set of 10 to 15 repetitions of 8 to 10 exercises that used the major muscle groups should be performed. Compared to young subjects, resistance training in elderly produces an increase strength that is lower in absolute term but similar relative to muscle mass. The increased muscle size is relatively moderate (between 5 and 10%) compared to the increased in muscle strength. Most of the large increased in strength resides in neural adaptation of the motor unit pathway [5]. Discontinuation of resistance training results in a rapid detraining [217]. However, several reports suggest that maintenance of benefits from resistance training is possible with as light as one per week exercise program [218]. However, organizing resistance training may be challenging in frail elderly subjects and some practitioners are reluctant to prescribe high intensity in elderly subjects. Currently, only 12% of the United-States elderly population performs strength training at least twice a week [219]. Then, new approaches may be relevant in frail elderly population. Recent works have suggested that whole body vibration exercise may be a safe, simple and effective way to exercise musculoskeletal structures [220-222]. This countermeasure to disuse could be relevant in elderly subject who can not be involved in usual resistance training such as weight lifting. Beneficial effects on joint pain and cardiovascular system have also been reported [220]. However, more studies are needed to ascertain beneficial effect and safety of whole body vibration exercise on sarcopenia in elderly [220].
  • falls are a significant problem for older adults and that treatment and complications result in high healthcare costs. To prevent falls through the development of effective screening, prevention, and rehabilitation programs, it is important to identify modifiable risk factors for falling.
  • Although muscle weakness appears to be an independent risk factor for falls, there is not strong evidence supporting strength training in preventive programs.” Most studies used some combination of resistance exercises, balance exercises, endurance exercises, and flexibility, but only three of these studies59–61 isolated resisted muscle strength training as the independent variable.
  • 14 sujets 1 jambe immobilisé et l’autre pas. Reponse a l’apport d’aa.
  • 25 poeple in each group Leg extension and flexion The total volume of exercise was identicale. The curve Past 60 % is flat and so the is no benefit to train over 60-70 %
  • Robust evidence in several studies indicate that resistance training such as weight lifting increases myofibrillar muscle protein synthesis Yarasheski, K.E., J.J. Zachwieja, and D.M. Bier, Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women. Am J Physiol, 1993. 265(2 Pt 1): p. E210-4. Hasten, D.L., et al., Resistance exercise acutely increases MHC and mixed muscle protein synthesis rates in 78-84 and 23-32 yr olds. Am J Physiol Endocrinol Metab, 2000. 278(4): p. E620-6. Resistance training such as weight lifting increases muscle mass and strength even in the frail elderly. Jozsi, A.C., et al., Changes in power with resistance training in older and younger men and women. J Gerontol A Biol Sci Med Sci, 1999. 54(11): p. M591-6. Welle, S., C. Thornton, and M. Statt, Myofibrillar protein synthesis in young and old human subjects after three months of resistance training. Am J Physiol, 1995. 268(3 Pt 1): p. E422-7. Fiatarone, M.A., et al., Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med, 1994. 330(25): p. 1769-75. Yarasheski, K.E., et al., Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men >/=76 yr old. Am J Physiol, 1999. 277(1 Pt 1): p. E118-25. Ivey, F.M., et al., Effects of age, gender, and myostatin genotype on the hypertrophic response to heavy resistance strength training. J Gerontol A Biol Sci Med Sci, 2000. 55(11): p. M641-8. Cress, M.E., et al., Exercise: effects on physical functional performance in independent older adults. J Gerontol A Biol Sci Med Sci, 1999. 54(5): p. M242-8. Hikida, R.S., et al., Effects of high-intensity resistance training on untrained older men. II. Muscle fiber characteristics and nucleo-cytoplasmic relationships. J Gerontol A Biol Sci Med Sci, 2000. 55(7): p. B347-54. Hagerman, F.C., et al., Effects of high-intensity resistance training on untrained older men. I. Strength, cardiovascular, and metabolic responses. J Gerontol A Biol Sci Med Sci, 2000. 55(7): p. B336-46.
  • AMP/ATP augmente pendant l’activité physique. Proteins synthesis especailly o fthe mitochondrial proteins
  • AMP/ATP augmente pendant l’activité physique. Proteins synthesis especailly o fthe mitochondrial proteins
  • This mechanism explaine why the protein synthesis is increase and seems related to the period of the energy recuperation
  • The other metabolic factor These mecanism explain why resistance training is necessary to stimulate protein synthesis
  • Growth factor ( MyoD, MRF4, Myogenin, Myf5) The neurological factor is respossible of the typology fo the muscle (Slow fiber or quick fibers)
  • Growth factor ( MyoD, MRF4, Myogenin, Myf5) Ratio of MyoD, MRF4, Myogenin, Myf5 The neurological factor is respossible of the typology fo the muscle (Slow fiber or quick fibers)
  • The titine is able to integrate the variation of the length of the sarcomere This système allow to understand how passive streching is able to maintain muscle mass
  • Potential sites and physiological mechanisms that regulate strength. The neuromuscular system contains several potential sites that can affect voluntary force or power production, such as excitatory drive from supraspinal centers, a-motoneuron excitability, antagonistic muscle activity, motor unit recruitment and rate coding, neuromuscular transmission, muscle mass, excitation-contraction (E-C) coupling processes, and muscle morphology and architecture. There is evidence of aging-induced alterations at nearly every denoted site within the system such as, but not limited to, the following: (1) decreased cortical excitability (36); (2) decreased spinal excitability (29); (3) decreased maximal motor unit discharge rate (28); (4) slowed nerve conduction (37); (5) alterations in muscle architecture (reduced fascicle length and pennation angle, and tendon stiffness) (33); (6) decreased muscle mass (sarcopenia) (12); (7) increased myocellular lipid content (38); (8) E-C uncoupling (i.e., decreased number of dihydropyridine receptors) (35). Please see Figure 3 for a more detailed processes related to dynapenia.
  • Potential sites and physiological mechanisms that regulate strength. The neuromuscular system contains several potential sites that can affect voluntary force or power production, such as excitatory drive from supraspinal centers, a-motoneuron excitability, antagonistic muscle activity, motor unit recruitment and rate coding, neuromuscular transmission, muscle mass, excitation-contraction (E-C) coupling processes, and muscle morphology and architecture. There is evidence of aging-induced alterations at nearly every denoted site within the system such as, but not limited to, the following: (1) decreased cortical excitability (36); (2) decreased spinal excitability (29); (3) decreased maximal motor unit discharge rate (28); (4) slowed nerve conduction (37); (5) alterations in muscle architecture (reduced fascicle length and pennation angle, and tendon stiffness) (33); (6) decreased muscle mass (sarcopenia) (12); (7) increased myocellular lipid content (38); (8) E-C uncoupling (i.e., decreased number of dihydropyridine receptors) (35). Please see Figure 3 for a more detailed processes related to dynapenia.
  • in which different training protocols are compared.
  • To understand what happen at the cellular level some author have developped a theorical approach with mecanical and biochimical stimuli which stimulate the muscular membrane with all the pathway to transduction, adaptation and effect.
  • If we just considere the external factor, copier coller
  • Why and how do we build muscle when exercising
  • Two kind of hormones : 1 – Hormone that play a role on the devemoppment of muscle mass 2 – Hormons that play a role in the différentiation of the muscle cell These hormon play a role all the life long but they influence decrease with age and the steroid have the higher impact adolescence
  • Physical activity increasee the level of steroid but increase is two small to explain the increase in mass mass. On the other hand, the increase in somatotrope axis, and especially the paracrine and autocrine effect of the IGF-1 stimule the differenciation and proliferation of the satllite cell and the myoblaste which resulte in an increase muscle mass. Moreover,
  • The relation of physical activity and hormons is influence by differents factors such as age, Nutrition (Protide and glucides) et the type of physique activity with a main role of the recuperation period. Leucine before RST decrease GH, TEsto et incerease insuline (hulmi Finland 2005)
  • Only RCT Context of resistance training The changes a negligable
  • It the same for muscle strength Very low effect There are even fewer study 5 Kg meat = 20 g of creatine Success in COPD in mean lean mass but not in walking speed. So my take on it, You need to do good resistance training and you probably need to a suffisant amount of food but whether nutrition supplement on top of that is efficient is very questionnable.
  • Why and how do we build muscle when exercising
  • When you do resistance exercise, With can cause more damage than ther are at the biginning, It is the stimulus for satellite cell activation Which is the source of IGF-1 that appeare in the muscle This stimulate aa intake in the muscle , in the sontexte of aving anough food, You can then result in hypertrophy and hyperplasia
  • It is clearly demonstrated that the developpement of muscle mass is related to the amont of calorie intake and the amont of of proteine in the diet. For the protein requirement The minimum to be just in equilibrium…
  • Ce qui nous améne au paradoxe que plus on est fragile, plus on est a risque de fracture, plus on peut bénéficié du traitement et moins on a accés au traitement
  • Ce qui nous améne au paradoxe que plus on est fragile, plus on est a risque de fracture, plus on peut bénéficié du traitement et moins on a accés au traitement
  • Ce qui nous améne au paradoxe que plus on est fragile, plus on est a risque de fracture, plus on peut bénéficié du traitement et moins on a accés au traitement
  • Nutrition In elderly population, intentional or not intentional weight loss in normal, overweight or obese elderly results in loss of muscle mass and increased rate of death [223]. Weight loss should be avoided probably over the seventh decade of life [224, 225]. It is particularly true if there is a reduction of the BMI and no reduction of the waist circumference because waist circumference is related first to cardiovascular disease while BMI is related to total body mass and lean mass. In malnourished elderly, poor protein intake is probably a barrier to obtain muscle tissue and strength gain from intervention such as resistance training. Greater protein intake in elderly and especially in frail elderly (higher than the recommended 0.8g/kg body weight per day) may minimize the sarcopenic process [226]. However, it is not clear whether protein supplementation in elderly without malnourishment can enhance muscle mass and muscle strength. Yet, protein supplementation alone or in association with physical training has currently been unsuccessful (see [115] for references). However, new approaches, based on more specific nutriment, including essential amino acid and especially leucine [227] suggested an anabolic effect of essential amino acids. It has been recently reported that essential amino acids stimulate protein anabolism in elderly whereas nonessential amino acids add no effect in association to the essential amino acids [183]. In supraphysiologic concentration, leucine stimulates the muscle protein synthesis [227]. This may be related to a direct effect of leucine on the initiation of mRNA translation. Recent reports have suggested, that amino acids are inefficient on muscle protein synthesis if there do not contain enough leucine [228]. These studies suggest that both quantity and quality of the amino acids are important factors for protein synthesis. Schedule of the protein supplementation may also be relevant to improved muscle protein synthesis. In human, it has been demonstrated that a large amount of amino acid supplementation in one meal a day was more efficient than spread protein feeding to increased the anabolic effect [229]. These reports suggest that an anabolic effect of protein supplementation may be maximize if perform with a large amount of a highly efficient nutritional supplement (such as essential amino acid and especially leucine) one time a day. However, no randomized clinical trial actually supports the benefit of this specific approach on muscle mass synthesis. In association to strength training, the moment of the protein supplementation may also impact on the muscle tissue anabolism. Compared to protein supplement taken between the resistance training sessions, protein supplementation taken immediately after the resistance training may produced a 25% increase in quadriceps muscle cross-sectional area. No increase was reported if the supplementation was taken at a distance time of the training [230]. Prevention of sarcopenia should be engaged all life long and not only in elders. The persisting influence of specifics exposures at critical period of the development of organs such as the muscle tissue, so called the phenomenon of programming, may have a major impact on the risk of sarcopenia. It has been shown that poor infant growth was associated with an increase risk of falls mediate partly through sarcopenia [231]. Birth weight is also associated with sarcopenia [163]. Evidence suggests that early life nutrition have a dramatic impact in adulthood muscle mass. Effective intervention may be considered across the whole life course.
  • Relation between Protein intake and Total Energy Intake
  • Relation between Protein intake and Total Energy Intake
  • contrindication
  • contrindication
  • 1 rolland

    1. 1. Physical activity and the musculo-skeletal system and the prevention of falls Yves Rolland 4th International Seminar on Preventive Geriatrics & 1st International Seminar on Geriatric Rehabilitation
    2. 2. OUTLINE I- Introduction II- Sarcopenia is a risk factor for falls III- Inactivity IV- Resistance training V - Conclusion
    3. 3. OUTLINE I- Introduction II- Sarcopenia is a risk factor for falls III- Inactivity IV- Resistance training V - Conclusion
    4. 4. 75 Age (years) Muscle Mass (kg) Influence of Age on Skeletal Muscle Mass Janssen et al., J Appl Physiol 89:81-88, 2000 15 25 35 45 55 65 85 0 10 20 30 40 50 Introduction Men Women
    5. 5. Age (years) Muscle Mass (kg) 75 15 25 35 45 55 65 85 0 10 20 30 40 50 Influence of Age on Skeletal Muscle Mass Introduction Men Women
    6. 6. Age (years) Muscle Mass (kg) Janssen et al., J Appl Physiol 89:81-88, 2000 75 15 25 35 45 55 65 85 0 10 20 30 40 50 Physical activity Influence of Age on Skeletal Muscle Mass Introduction Men Women
    7. 7. Age (years) Muscle Mass (kg) Janssen et al., J Appl Physiol 89:81-88, 2000 75 15 25 35 45 55 65 85 0 10 20 30 40 50 Physical activity « Peak muscle mass » Influence of Age on Skeletal Muscle Mass Introduction Men Women
    8. 8. OUTLINE I- Introduction II- Sarcopenia is a risk factor for falls III- Inactivity IV- Resistance training V - Conclusion
    9. 9. Physical activity, falls and fractures Frail elderly Falls Reduce physical activity Loss of muscle mass and strength Fear of falling Fractures
    10. 10. Physical activity, falls and fractures INCIDENCE OF FRACTURES OSTEOPOROSIS FALLS 75 ys 85 ys 65 ys Women Men 75 ys
    11. 11. number of FALLS (per person year) Number of FRACTURE (per person year) BONE MINERAL DENSITY Sambrook PN et al. Osteoporos Int (2007) 18:603–610 Physical activity, falls and fractures
    12. 12. Physical activity, falls and fractures <ul><li>At least 2 difficulties : Climbing stairs, walk 5’ outside, rising from a chair, … </li></ul>Risk of falls and hip fracture <ul><li>Having poor physical performances </li></ul><ul><li>Standing chair test, handgrip strength </li></ul><ul><li>Timed up & go test > 20 secondes </li></ul><ul><li>Walking speed < 1ms -1 , </li></ul><ul><li>One leg balance < 5 secondes </li></ul><ul><li>Being inactive </li></ul>Stel et al. Osteoporos Int (2004) 15: 742–750
    13. 13. <ul><li>Lower extremity weakness </li></ul><ul><li>OR = 1.76 [1.31-2.37] for any fall </li></ul><ul><li>OR = 3.06 [186-5.04] for recurrents falls </li></ul>J Am Geriatr Soc (2004)
    14. 14. Physical activity, falls and fractures J Am Geriatr Soc (2004) “ Although muscle weakness appears to be an independent risk factor for falls, there is not strong evidence supporting strength training in preventive programs.” Effectiveness of strengthening exercises for preventing falls ?
    15. 15. The most effective intervention was a multifactorial falls risk assessment and management programme.
    16. 16. The most effective intervention was a multifactorial falls risk assessment and management programme.
    17. 17. Physical activity, falls and fractures Rantanen et al J Am Geriatr Soc (2001) 49 : 21-27 COIMPAIRMENT+++
    18. 18. OUTLINE I- Introduction II- Sarcopenia is a risk factor for falls III- Inactivity IV- Resistance training V - Conclusion
    19. 19. <ul><li>Hormonal modifications </li></ul>HPA axis dysregulation Motoneuron denervation Inflammation Oxidative stress Apoptosis Reduced protein synthesis Anemia / tissue oxygenation Protein diet deficiency Disuse / physical inactivity Etiology of SARCOPENIA
    20. 20. % of subjects engaged in sedentary leisures activities Insee 2005 France % of subjects engaged in moderate to high intensity physical activities age % %
    21. 21. Inactivity Effect of 10 days of bed rest in older adults % % Kortebein et al. JAMA 2007 10 days of bed rest = -1.5 kg of LM and -15% leg Muscle Strength
    22. 22. Age (years) Muscle Mass (kg) Influence of Age on Skeletal Muscle Mass Janssen et al., J Appl Physiol 89:81-88, 2000 25 year old man 65 year old man
    23. 23. Janssen et al., J Appl Physiol 89:81-88, 2000 - 1.5 kg per 10 bed-rest - 2 kg per decade in men - 1 kg per decade in women Influence of Age on Skeletal Muscle Mass Age (years) Muscle Mass (kg) Muscle Mass (kg) 0 10 20 30 40 50 15 25 35 45 55 65 75 85 Women Men
    24. 24. Changes in volume and muscle strength after 30 days of bed-rest or 28 day of spatial flight Convertino 1991 - - - - - 25 - 20 - 15 - 10 - 5 0 % Skylab 28 days Bed rest 30 days Weight Strength extension Strength Flexion Mean ± SD Leg volume
    25. 25. Changes in volume and muscle strength after 30 days of bed-rest or 28 day of spatial flight Convertino 1991 - - - - - 25 - 20 - 15 - 10 - 5 0 % Skylab 28 days Bed rest 30 days Weight Strength extension Strength Flexion Mean ± SD Leg volume Bed rest 10 days In elderly subject
    26. 26. OUTLINE I- Introduction II- Sarcopenia is a risk factor for falls III- Inactivity IV- Resistance training V - Conclusion
    27. 27. How Sarcopenia should be addressed ? <ul><li>Optimize muscle mass adaptation to progressive resistance training in older people with evidence-based training techniques </li></ul>Resistance training
    28. 28. Resistance Rapid type of mysosin Glycolytic metabolism Low mitochondria density Endurance Slow type of myosin Oxidative metabolism High mitochondria density Nature of the mechanical constraints Nervous stimulation Hormonal response Nutrition Genetic (25 – 50%)
    29. 29. Can habitual physical activity prevent sarcopenia ? Loss of leg muscle mass Klitgaard, Acta Physiol Scandi 1990
    30. 30. Clarence Bass 15 years 60 years 45 years 30 years 72 years
    31. 31. Anabolic resistance of muscle to exercise in older men MJ Rennie Biochem Soc Trans 2007
    32. 32. Resistance training and muscle strength in elderly Mean age Type of training Resist. duration (week) Mean increase Aniansson 71 Dyn + Stat low 12 9-22% Larsson 22-65 Dynam low 15 3-7% Moritani 22-70 Dynam high 8 23-30% Kauffman 23-69 Statique high 6 72-95% Frontera 60-72 Dynam high 12 107-227% Hagberg 70-79 Dynam moderate 26 9-18% Fiatarone 90 Dynam high 8 174% Nichols 67 Dynam high 6 5-65% Judje 80 Dynam high 13 13% Judje 82 Dynam high 12 25-32%
    33. 33. Resistance training in frail elderly subjects Fiatarone et al., JAMA, 1990 8 weeks J0 30 25 20 15 10 5 0 Muscle Strength kg ( Leg ) 7,6 kg 19,3 kg P < 0,0001 Increase : 174%
    34. 34. Once-weekly resistance exercise improves muscle strength and neuromuscular performance in older adults Taaffe et al. JAGS 1999 Knee extension strength (kg)
    35. 35. Increase in muscle mass Hypertrophy (muscle fibers area) Hyperplasia (number of fibers) Resistance training Stretching Mechanical overload and skeletal muscle fiber hyperplasia: a meta-analysis George Kelley J Appl Physiol 81: 1584-1588, 1996
    36. 36. Results of strength training Time 8 – 12 weeks Strength Muscle mass Nerve Improvement
    37. 37. What is the best resistance training program to treat sarcopenia ?
    38. 38. Guidelines and statement on resistance training Circulation. 2007; 116:572-584
    39. 39. OUTLINE I- Introduction II- Sarcopenia is a risk factor for falls III- Inactivity IV- Resistance training V- Conclusion
    40. 40. THM <ul><li>Sarcopenia is a risk factor for falls </li></ul><ul><li>Prevention of falls rely on multidimentional intervention </li></ul><ul><li>Avoid disuse, inactivity, bedrest </li></ul><ul><li>No pharmacological or behavioral intervention has proven to be as efficacious as resistance training </li></ul><ul><li>Resistance can be performed by frail elderly </li></ul><ul><li>Anabolic resistance of muscle to exercise in elderly </li></ul><ul><li>Discontinuation of resistance training results in a rapid detraining </li></ul>
    41. 44. <ul><li>Organizing resistance training may be challenging in frail elderly </li></ul><ul><li>Maintaining an active life (walking) may help to prevent sarcopenia </li></ul><ul><li>Benefits of hormones in addition to RT is actually not proven </li></ul><ul><li>Optimal RT program in not well-known </li></ul><ul><li>Eat soon after exercise (EAA) </li></ul><ul><li>Maintain proteino-energetic ratio at a upper level </li></ul><ul><li>Fulfill energy requirement </li></ul>THM
    42. 45. Physical activity, falls and fractures Frail elderly Falls Reduce physical activity Loss of muscle mass and strength Fear of falling Fractures
    43. 46. Physical activity, falls and fractures INCIDENCE OF FRACTURES OSTEOPOROSIS FALLS 75 ys 85 ys 65 ys Women Men 75 ys
    44. 47. number of FALLS (per person year) Number of FRACTURE (per person year) BONE MINERAL DENSITY Sambrook PN et al. Osteoporos Int (2007) 18:603–610 Physical activity, falls and fractures
    45. 48. Physical activity, falls and fractures <ul><li>At least 2 difficulties : Climbing stairs, walk 5’ outside, rising from a chair, … </li></ul>Risk of hip fracture <ul><li>Having poor physical performances </li></ul><ul><li>Standing from a chair, handgrip strength </li></ul><ul><li>Timed up & go test > 20 secondes </li></ul><ul><li>Walking speed < 1ms -1 , One leg balance < 5 secondes </li></ul><ul><li>Being inactive </li></ul>Stel et al. Osteoporos Int (2004) 15: 742–750
    46. 49. <ul><li>Lower extremity weakness </li></ul><ul><li>OR = 1.76 [1.31-2.37] for any fall </li></ul><ul><li>OR = 3.06 [186-5.04] for recurrents falls </li></ul>J Am Geriatr Soc (2004)
    47. 50. Physical activity, falls and fractures J Am Geriatr Soc (2004) “ Although muscle weakness appears to be an independent risk factor for falls, there is not strong evidence supporting strength training in preventive programs.” Effectiveness of strengthening exercises for preventing falls ?
    48. 51. Physical activity, falls and fractures Rantanen et al J Am Geriatr Soc (2001) 49 : 21-27
    49. 52. The most effective intervention was a multifactorial falls risk assessment and management programme.
    50. 53. Clinical syndrome of Vitamin D deficiency include Muscle weakness Muscle pain Waddling gait Schott GD, Wills MR: Muscle weakness in osteomalacia. Lancet. 1976 Treatments Vitamin D
    51. 54. Treatments 2 to 12 months of 800 IU vitamin D3 result to 4 to 11% gain in lower extremity strength 28% improvement in body sway Pfeifer M et al. Osteoporos Int, 2009 800 UI Vitamin D3
    52. 55. PHYSICAL ACTIVITY YES What we know YES Introduction
    53. 56. What we do not know ??? PHYSICAL ACTIVITY Introduction
    54. 57. Immobilization induces anabolic resistance in muscle synthesis with low or high dose aa infusion Glover EI et al. J Phys 2008
    55. 58. Signaling pathways that control Atrogin-1 expression and protein turn-over during Atrophy and Hypertrophy PHYSICAL ACTIVITY INACTIVITY ATROPHY HYPERTROPHY
    56. 59. Anabolic resistance of muscle to exercise in older men MJ Rennie Biochem Soc Trans 2007
    57. 60. Resistance Training <ul><li>Robust evidences indicate that resistance training </li></ul><ul><li>increases myofibrillar muscle protein synthesis </li></ul><ul><li>Yarasheski, K.E., J.J. Zachwieja, and D.M. Bier, Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women. Am J Physiol, 1993. 265(2 Pt 1): p. E210-4. </li></ul><ul><li>Hasten, D.L., et al., Resistance exercise acutely increases MHC and mixed muscle protein synthesis rates in 78-84 and 23-32 yr olds. Am J Physiol Endocrinol Metab, 2000. 278(4): p. E620-6. </li></ul><ul><li>increases muscle mass and strength even in the frail elderly. </li></ul><ul><li>Jozsi, A.C., et al., Changes in power with resistance training in older and younger men and women. J Gerontol A Biol Sci Med Sci, 1999. 54(11): p. M591-6. </li></ul><ul><li>Welle, S., C. Thornton, and M. Statt, Myofibrillar protein synthesis in young and old human subjects after three months of resistance training. Am J Physiol, 1995. 268(3 Pt 1): p. E422-7. </li></ul><ul><li>Fiatarone, M.A., et al., Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med, 1994. 330(25): p. 1769-75. </li></ul><ul><li>Yarasheski, K.E., et al., Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men >/=76 yr old. Am J Physiol, 1999. 277(1 Pt 1): p. E118-25. </li></ul><ul><li>Ivey, F.M., et al., Effects of age, gender, and myostatin genotype on the hypertrophic response to heavy resistance strength training. J Gerontol A Biol Sci Med Sci, 2000. 55(11): p. M641-8. </li></ul><ul><li>Cress, M.E., et al., Exercise: effects on physical functional performance in independent older adults. J Gerontol A Biol Sci Med Sci, 1999. 54(5): p. M242-8. </li></ul><ul><li>Hikida, R.S., et al., Effects of high-intensity resistance training on untrained older men. II. Muscle fiber characteristics and nucleo-cytoplasmic relationships. J Gerontol A Biol Sci Med Sci, 2000. 55(7): p. B347-54. </li></ul><ul><li>Hagerman, F.C., et al., Effects of high-intensity resistance training on untrained older men. I. Strength, cardiovascular, and metabolic responses. J Gerontol A Biol Sci Med Sci, 2000. 55(7): p. B336-46. </li></ul>
    58. 61. Carson and Wei J Appl Physio 2000   protein RhoA transcription FAK Integrins  p160 Rock paxillin PIP2 Ca 2+ calcineurin Transcription factor NFAT3 GATA4 Adhesion calcineurin transcription factor Transcription factor Integrins Mechanical constraint on cell membrane
    59. 62. Metabolic factors ↑ AMP/ATP Activation of AMPK PROTEINS SYNTHESIS - During Physical activity
    60. 63. PROTEINS SYNTHESIS During recuperation ↓ AMP/ATP Deactivation of AMPK + Metabolic factors Metabolic factors ↑ AMP/ATP Activation of AMPK PROTEINS SYNTHESIS - During Physical activity
    61. 64. [AMPK] = SENSOR of the energetic status in the fiber = regulator of the BIODISPONIBILITY of the AA in the fiber PROTEINS SYNTHESIS - + Metabolic factors
    62. 65. HYPOXEMIA ↑ Hypoxic Inductible Factor (HIP) ↑ Vascular Endothelial Growth Factor (VEGF) PROTEINS SYNTHESIS + Metabolic factors
    63. 66. neuromuscular synapse Nerve ↑ Calcium Myogenin Family Ratio of MyoD, MRF4, Myogenin, Myf5 Synthesis and type of Heavy Myosin chain Muscle fiber Sui et al. J Appl Physio 2000 Neurological factors
    64. 67. Nerve Hormones Thyroids Typology of the fiber : Type I, II neuromuscular synapse Nerve ↑ Calcium Myogenin Family Ratio of MyoD, MRF4, Myogenin, Myf5 Synthesis and type of Heavy Myosin chain Muscle fiber Sui et al. J Appl Physio 2000 Neurological factors
    65. 68. Effect of stretching TITIN
    66. 69. Decreased cortical excitability Decreased spinal excitability Decreased maximal motor unit discharge rate slowed nerve conduction 5 Alterations in muscle architecture 6 & 7 Decreased muscle mass; Increased myocellular lipid content E-C uncoupling Potential sites and physiological mechanisms that regulate strength Journal of Gerontology: Medical sciences 2008, vol 63A, n°8, 829-834
    67. 70. Decreased cortical excitability Decreased spinal excitability Decreased maximal motor unit discharge rate slowed nerve conduction 5 Alterations in muscle architecture 6 & 7 Decreased muscle mass; Increased myocellular lipid content E-C uncoupling Potential sites and physiological mechanisms that regulate strength Journal of Gerontology: Medical sciences 2008, vol 63A, n°8, 829-834 Resistance training ?
    68. 71. <ul><li>« To determine the most appropriate design of the exercise program for functional improvement or prevention of loss of function, more high-quality trials are needed … » </li></ul>
    69. 72. Toigo and Bouteiller 2006 Eur J Appl Physiol
    70. 73. Toigo and Bouteiller 2006 Eur J Appl Physiol
    71. 74. Endurance training and sarcopenia <ul><li>Aerobic exercise does not contribute as much to muscle hypertrophy as resistance exercises, but they stimulate muscle protein synthesis </li></ul><ul><li>Sheffield-Moore, M., et al., Postexercise protein metabolism in older and younger men following moderate-intensity aerobic exercise. Am J Physiol Endocrinol Metab, 2004. 287(3): p. E513-22. </li></ul><ul><li>Aerobic exercise stimulates satellite cell activation and increases muscle fibers area. </li></ul><ul><li>Coggan, A.R., et al., Skeletal muscle adaptations to endurance training in 60- to 70-yr-old men and women. J Appl Physiol, 1992. 72(5): p. 1780-6. </li></ul><ul><li>Charifi, N., et al., Effects of endurance training on satellite cell frequency in skeletal muscle of old men. Muscle Nerve, 2003. 28(1): p. 87-92. [68, 69]. </li></ul>
    72. 75. Muscle substrate utilization : Effect of endurance training O 2 ml/min Kiens et al. J Physiol
    73. 76. Fried and Walston, 1998
    74. 77. Fried and Walston, 1998
    75. 78. Obesity, physical activity and sarcopenia <ul><li>Loss of </li></ul><ul><li>muscle mass </li></ul>lower physical activity Obesity Catabolism > Anabolism
    76. 79. OUTLINE I- Background II- Inactivity III- Resistance Training IV - Endur ance V- Hormones VI- Nutrition VII- Conclusion
    77. 80. Physical activity, sarcopenia and hormones ↑ MUSCLE MASS STEROÏDES SOMATOTROPE AXIS INSULINE ↑ DIFFERENCIATION ↑ PROLIFERATION Gharge et Rudnicki, Physio Rev 2004; Adamo and Farrar, Ageing Res Rev2006
    78. 81. Physical activity, sarcopenia and hormones PHYSICAL ACTIVITY ↑ MUSCLE MASS STEROÏDES SOMATOTROPE AXIS INSULINE ↑ DIFFERENCIATION ↑ PROLIFERATION Gharge et Rudnicki, Physio Rev 2004; Adamo and Farrar, Ageing Res Rev2006
    79. 82. AGE NUTRITION TYPE OF EXERCISE RECUPERATION PHYSICAL ACTIVITY ↑ MUSCLE MASS STEROÏDES SOMATOTROPE AXIS INSULINE ↑ DIFFERENCIATION ↑ PROLIFERATION Gharge et Rudnicki, Physio Rev 2004; Adamo and Farrar, Ageing Res Rev2006
    80. 83. Physical activity, nutrition and sarcopenia Effect of dietary supplementation on lean mass with resistance exercise : A meta-analysis Nissen SL et al. J Appl Physiol 2003 HMB; Beta-hydroxy-beta-methylbutyrate; DHEA; Dihydroepiandrosterone
    81. 84. Effect of dietary supplementation on strength gains with resistance exercise : A meta-analysis Nissen SL et al. J Appl Physiol 2003 Physical activity, nutrition and sarcopenia HMB; Beta-hydroxy-beta-methylbutyrate; DHEA; Dihydroepiandrosterone
    82. 85. <ul><li>Benefit of hormones in addition to RT is not demonstrated in elderly people </li></ul>VALIDATED TREATMENTS AND THERAPEUTIC PERSPECTIVES REGARDING PHYSICAL ACTIVITIES THM 4
    83. 86. OUTLINE I- Background II- Inactivity III- Resistance Training IV - Endur ance V- Hormones VI- Nutrition VII- Conclusion
    84. 87. Effect of progressive resistance training (PRT) on muscle fibers area in frail nursing home residents Fiatarone, AJP Ficsit study 1999 Type 1 fiber area Type 2 fiber area % change
    85. 88. Proposed mechanism of adaptation within skeletal muscle From Maria A. Fiatarone Singh, V e Nestlé Symposium Lausanne 2008
    86. 89. Nutritional factors Tarnopolsky et al. J Appl Phys 1988 Protein Intake Protein Excretion NITROGEN BALANCE Minimum Protein Intake 0.8 g/kg/j adult 1.2 g/kg/j resistance training 1.6 g/kg/j endurance
    87. 90. Increases in muscle fibre area and muscle cross sectional area after resistance training with immediate feeding and delayed feeding by 2 hours Esmark et al. 2001
    88. 91. <ul><li>Eat soon after exercise (EAA) </li></ul><ul><li>Maintain proteino-energetic ratio at a upper level </li></ul><ul><li>Fulfill energy requirement </li></ul>VALIDATED TREATMENTS AND THERAPEUTIC PERSPECTIVES REGARDING PHYSICAL ACTIVITIES THM 5
    89. 92. Activité physique, performances fonctionnelles, chutes <ul><li>Déclarer au moins 2 difficultés </li></ul><ul><li>pour monter les escaliers, marcher 5 minutes dehors, se lever d’une chaise, s’habiller, utiliser les transport en commun </li></ul>Risque de fracture de hanche <ul><li>Avoir de mauvaises performances fonctionnelles </li></ul><ul><li>Test de levée de chaise, handgrip strength </li></ul><ul><li>Timed up & go test > 20 secondes </li></ul><ul><li>Vitesse de marche < 1ms -1 , Station unipodale < 5 secondes </li></ul><ul><li>Etre inactif </li></ul>Stel et al. Osteoporos Int (2004) 15: 742–750
    90. 93. Equilibre Taux d’incapacité sévère à la marche pour 100 pers. année Rantanen et al J Am Geriatr Soc (2001) 49 : 21-27 Force quadricipitale Activité physique, performances fonctionnelles, chutes
    91. 94. Equilibre Taux d’incapacité sévère à la marche pour 100 pers. année Rantanen et al J Am Geriatr Soc (2001) 49 : 21-27 Force quadricipitale Activité physique, performances fonctionnelles, chutes
    92. 95. Sujet adulte Sujet âgé Sarcopénie Diminution de la masse et de la force
    93. 97. Nutrition <ul><li>In malnourished elderly, poor protein intake is probably a barrier to obtain muscle tissue and strength gain </li></ul><ul><li>It is not clear whether protein supplementation in elderly without malnourishment can enhance muscle mass and muscle strength. </li></ul><ul><li>More specific nutriment, including essential amino acid and especially leucine stimulate protein synthesis. </li></ul><ul><li>The schedule of the protein supplementation may also impact on the muscle tissue anabolism. </li></ul><ul><li>Early life nutrition have a dramatic impact in adulthood muscle mass </li></ul>Therapeutic approaches
    94. 98. Conclusion <ul><li>Understanding and treating sarcopenia could have a dramatic impact on the elderly disability process. However, research is still needed to adopt a definitive operational clinical definition of sarcopenia in practice and clinical research. Sarcopenia is a multifactorial condition that requires a multi-modal therapeutic approach. Prevention of the loss of muscle mass and muscle strength will be relevant if it prevents the loss of physical performances and disability. Defining target elderly populations for specific treatment in clinical trial is yet an important issue. Endpoint should be the prevention of mobility disability and not only the prevention of muscle mass, muscle strength or muscle quality. </li></ul><ul><li>Actually, strength training is the only efficient therapeutic to prevent sarcopenia. So far, there are no pharmacological approaches that have proven definitive evidence to prevent decline in physical function and sarcopenia. However, on-going and future pharmacological clinical trials may radically change our therapeutic approach of mobility disability in elderly. </li></ul>
    95. 99. Training and intensity
    96. 100. Signaling pathways that control Atrogin-1 expression and protein turn-over during Atrophy and Hypertrophy
    97. 101. Signaling pathways that control Atrophy and Hypertrophy
    98. 102. Signaling pathways that control Atrophy and Hypertrophy
    99. 103. RESISTANCE TRAINING <ul><li>Duration </li></ul><ul><ul><li>8 to 12 weeks </li></ul></ul><ul><li>Frequency </li></ul><ul><ul><li>1 to 7 times a week </li></ul></ul><ul><li>Number of series </li></ul><ul><ul><li>3 to 6 </li></ul></ul><ul><li>Number of repetition </li></ul><ul><ul><li>Mean of 8 </li></ul></ul><ul><li>Level of charge </li></ul><ul><ul><li>80% RM </li></ul></ul>MAcaluso and De Vito., Eur J Appl Physiol 89:81-88, 2004
    100. 104. SEDENTARY Needs in Protein Intake ↑ when Total Energy Intake ↓ PHYSICAL ACTIVITY Needs in Protein Intake ↑ when Total Energy Intake ↓ Nutritional factors Protein Intake Protein Excretion NITROGEN BALANCE Tarnopolsky et al. J Appl Phys 1988
    101. 105. ↑ Glucose intake = ↑ Insulin = Anabolism During exercise, low glucose intake result in a negative protein balance Nutritional factors Protein Intake Protein Excretion NITROGEN BALANCE
    102. 106. Nitrogen balance and resistance training Campbell, Am J Clin Nutr 1999 Positive nitrogen balance induced by PRT even on protein intake of 0.8 g/kg/j in older adults
    103. 107. Prescription of Resistance training Contre-indication Circulation. 2007; 116:572-584
    104. 108. Recommandations for the initial prescription of Resistance training Circulation. 2007; 116:572-584
    105. 109. Change in thigh muscle with exercise and weight loss in older adults Deibert et al. Int J Obesity
    106. 110. Disuse / physical inactivity The Truth on Exercise <ul><li>4 in 10 women are engaged in the recommended levels of activity. </li></ul><ul><li>Activity decreases with age, and is less common among women than in men and among those with lower income and less education. </li></ul>Source: CDC. Behavioral Risk Factor Surveillance System, 2000

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