Improving Strength, Power, Muscle Aerobic Capacity, and Glucose Tolerance through Short-term Progressive Strength Training Among Elderly People
Summary
The effect of short-term resistance training on elderly people was investigated through the simultaneous use of several methods. Compared to a control group, many improvements were seen, including on muscle aerobic capacity, glucose tolerance, strength, power, and muscle quality (i.e., protein involved in cell signaling and muscle fiber type composition).
Abstract
This protocol describes the simultaneous use of a broad span of methods to examine muscle aerobic capacity, glucose tolerance, strength, and power in elderly people performing short-term resistance training (RET). Supervised progressive resistance training for 1 h three times a week over 8 weeks was performed by RET participants (71±1 years, range 65-80). Compared to a control group without training, the RET showed improvements on the measures used to indicate strength, power, glucose tolerance, and several parameters of muscle aerobic capacity. Strength training was performed in a gym with only robust fitness equipment. An isokinetic dynamometer for knee extensor strength permitted the measurement of concentric, eccentric, and static strength, which increased for the RET group (8-12% post- versus pre-test). The power (rate of force development, RFD) at the initial 0-30 ms also showed an increase for the RET group (52%). A glucose tolerance test with frequent blood glucose measurements showed improvements only for the RET group in terms of blood glucose values after 2 h (14%) and the area under the curve (21%). The blood lipid profile also improved (8%). From muscle biopsy samples prepared using histochemistry, the amount of fiber type IIa increased, and a trend towards a decrease in IIx in the RET group reflected a change to a more oxidative profile in terms of fiber composition. Western blot (to determine the protein content related to the signaling for muscle protein synthesis) showed a rise of 69% in both Akt and mTOR in the RET group; this also showed an increase in mitochondrial proteins for OXPHOS complex II and citrate synthase (both ~30%) and for complex IV (90%), in only the RET group. We demonstrate that this type of progressive resistance training offers various improvements (e.g., strength, power, aerobic capacity, glucose tolerance, and plasma lipid profile).
Introduction
Aging is associated with a loss of muscle mass (sarcopenia), strength, and power. Reduced strength, and probably even more importantly, power, results in immobility, an increased risk of injury, and a reduced quality of life. Resistance training is a well-known strategy to counteract sarcopenia and deteriorating muscle function. A rough estimate of muscle strength can be obtained from the load or number of achieved repetitions. However, this study obtained more detailed and accurate information on muscle function using an isokinetic dynamometer to gather information on the torque during isometric, concentric and eccentric contraction, as well as on the kinetics of force development.
Aerobic capacity, both at the whole-body level (VO2max) and in skeletal muscle, is reduced in elderly people. The decline in heart rate with age explains a large part of the decrease in VO2max1, but reduced muscle oxidative capacity, largely related to reduced physical activity2, does contribute. Impaired mitochondrial function may also be involved in the development of sarcopenia and insulin resistance3. The muscle aerobic capacity was assessed in muscle biopsies through biochemical analyses of the contents of mitochondrial enzymes and protein complexes located both in the matrix (i.e., citrate synthase) and the inner mitochondrial membrane. In addition, histochemical techniques were used to measure the effect of resistance training on muscle morphology (i.e., fiber type composition, fiber cross-sectional area, and capillary density). An alternative method to assess muscle aerobic capacity would be to use magnetic resonance spectroscopy to measure the rate of creatine phosphate resynthesis after exercise-induced depletion4. This method provides an estimate of the in vivo muscle aerobic capacity but cannot discriminate between mitochondrial dysfunction and circulatory disorders. Furthermore, the high costs of equipment limit the use of this technique in most laboratories. Aerobic capacity (VO2max and mitochondrial density) can be improved by endurance exercise in both young and old people5,6. However, the effect of resistance training on these parameters has been less investigated, especially in elderly subjects, and the results are conflicting7,8,9,10.
Type 2 diabetes is a widespread disease in the elderly population. Physical inactivity and obesity are major lifestyle-related factors explaining the increased incidence of type 2 diabetes. Low-intensity aerobic exercise is often recommended to subjects with reduced glucose tolerance. However, it is unclear how strength training in the elderly affects glucose tolerance/insulin sensitivity11,12. The most accurate way to measure insulin sensitivity is to use the glucose clamp technique, where the blood glucose is maintained constant by glucose infusion during conditions of elevated insulin13. The disadvantages with this technique are that it is time consuming and invasive (arterial catheterization) and requires special laboratory facilities. In this study, the oral glucose tolerance test, which is common in healthcare units, was used. This method is suitable when several subjects are to be investigated for a limited period of time.
The testing and timeline of the experimental procedure can be summarized as follows. Use three separate days for testing before and after an eight-week period, with the same arrangement and approximate time schedules (≥24 h between each day, Figure 1). On the first test day, measure: anthropometric data, such as height, body mass, fat-free mass (FFM), and upper leg circumference (i.e., 15 cm above the apex patellae in a relaxed supine position); submaximal cycling ability; and knee muscle strength, as described in steps 4 and 5. Take a muscle biopsy from the thigh on the second test day. For further descriptions, see step 6.1. Test oral glucose tolerance (OGTT) on the last testing day. For further descriptions, see step 7.1. Ask all participants to avoid vigorous physical activity for 24 h and to fast overnight prior to each test day. However, ask them to avoid strenuous physical activity for 48 h before the OGTT test day. Ask them to follow their normal everyday physical activity and diet habits. Note that pre- and post-intervention, both groups' self-reported food intake and type of foods were unchanged.
Figure 1: Experimental protocol. Schematic diagram. The timing between the three pre- and post-tests was similar for each subject and was at least 24 h. Further details are given in the text. This figure has been modified from Frank et al. Scand. J. Med. Sci. Sports. 2016: 26, 764-73.28 Please click here to view a larger version of this figure.
This study sought to investigate the effect of short-term resistance training in elderly people on muscle oxidative capacity and glucose tolerance. The second aim was to examine the effect on strength, power, and muscle qualitative improvements (i.e., proteins involved in cell signaling and muscle fiber type composition).
Protocol
Representative Results
Discussion
In this study, a number of techniques have been used to investigate the effects of short-term progressive resistance training on elderly subjects' muscle function/morphology, aerobic capacity, and glucose tolerance. The main finding was that, compared to a control group, many improvements occurred in muscle aerobic capacity, glucose tolerance, strength, power, and muscle quality (i.e., protein involved in cell signaling and muscle fiber composition). An increase was, for example, seen for: static, eccentric,…
Divulgations
The authors have nothing to disclose.
Acknowledgements
The authors are grateful to Andrée Nienkerk, Dennis Peyron, and Sebastian Skjöld for supervising the training sessions and several tests; to the subjects participating; to Tim Crosfield for language revision; and to the economic support from The Swedish School of Sport and Health Sciences.
Materials
| Western blot | |||
| Pierce 660nm Protein Assay Kit | Thermo Scientific, Rockford, IL, USA | 22662 | |
| SuperSignal West Femto Maximum Sensitivity Substrate | Thermo Scientific | 34096 | |
| Halt Protease Inhibitor Cocktail (100X) | Thermo Scientific | 78429 | |
| Restore PLUS Western Blot Stripping Buffer | Thermo Scientific | 46430 | |
| Pierce Reversible Protein Stain Kit for PVDF Membranes | Thermo Scientific | 24585 | |
| 10 st – 4–20% Criterion TGX Gel, 18 well, 30 µl | Bio-Rad Laboratories, Richmond, CA, USA | 567-1094 | |
| Immun-Blot PVDF Membrane | Bio-Rad | 162-0177 | |
| Precision Plus Protein Dual Color Standards | Bio-Rad | 161-0374 | |
| 2x Laemmli Sample Buffer | Bio-Rad | 161-0737 | |
| 10x Tris/Glycine | Bio-Rad | 161-0771 | |
| 2-Mercaptoethanol | Bio-Rad | 161-0710 | |
| Tween 20 | Bio-Rad | P1379-250ML | |
| Band analysis with Quantity One version 4.6.3.software | Bio-Rad | ||
| 1% phosphatase inhibitor coctail | Sigma-Aldrich, Saint Louis, Missouri, USA | ||
| Name | Company | Catalog Number | Comments |
| Antibodies | |||
| mTOR (1:1000) | Cell Signaling, Danvers, Massachusetts, USA | 2983 | |
| Akt (1:1000) | Cell Signaling, Danvers | 9272 | |
| Secondary anti-rabbit and anti-mouse HRP-linked (1:10000) | Cell Signaling, Danvers | ||
| Citrate synthase (CS) (1:1000) | Gene tex, San Antonio, California, USA | ||
| OXPHOS (1:1000) | Abcam, Cambridge, UK | ||
| Name | Company | Catalog Number | Comments |
| Equipment – Analysis of muscle samples | |||
| Bullet Blender 1.5 for homogenizing | Next Advance, New York, USA | ||
| Plate reader | Tecan infinite F200 pro, Männedorf, Switzerland | ||
| Name | Company | Catalog Number | Comments |
| Histochemistry | |||
| Mayer hematoxylin | HistoLab, Västra Frölunda, Sweden | 1820 | |
| Oil Red o | Sigma-Aldrich, Saint Louis, Missouri, USA | 00625-25y | |
| NaCl | Sigma-Aldrich | 793566-2.5 kg | |
| Cobalt Chloride | Sigma-Aldrich | 60818-50G | |
| Amylase | Sigma-Aldrich | A6255-25MG | |
| ATP | Sigma-Aldrich | A2383-5G | |
| Glycine | VWR-chemicals / VWR-international, Spånga, Sweden | 101196X | |
| Calcium Chloride | VWR-chemicals / VWR-international | 22328.262 | |
| Iso-pentane | VWR-chemicals / VWR-international | 24872.298 | |
| Etanol 96% | VWR-chemicals / VWR-international | 20905.296 | |
| NaOH | MERCK, Stockholm, Sweden | 1.06498.1000 | |
| Na acetate | MERCK | 1.06268.1000 | |
| KCl | MERCK | 1.04936.1000 | |
| Ammonium Sulphide | MERCK | U1507042828 | |
| Acetic acid 100% | MERCK | 1.00063.2511 | |
| Schiffs´ Reagent | MERCK | 1.09033.0500 | |
| Periodic acid | MERCK | 1.00524.0025 | |
| Chloroform | MERCK | 1.02445.1000 | |
| pH-meter LANGE | HACH LANGE GMBH, Dusseldorf, Germany | ||
| Light microscope | Olympus BH-2, Olympus, Tokyo, Japan | ||
| Cryostat Leica CM1950 | Leica Microsystems, Wetzlar, Germany | ||
| Leica software Leica Qwin V3 | Leica Microsystems | ||
| Gel Doc 2000 – Bio-Rad, camera setup | Bio-Rad Laboratories AB, Solna, Sweden | ||
| Software program Quantift One – 4.6 (version 4.6.3; Bio Rad) | Bio-Rad Laboratories AB, Solna, Sweden | ||
| Name | Company | Catalog Number | Comments |
| Oral glucos tolerance test, OGTT | |||
| Glukos APL 75 g | APL, Stockholm, Sweden | 323,188 | |
| Automated analyser Biosen 5140 | EKF Diagnostics, Barleben, Germany | ||
| Insulin and C-peptide in plasma kit ELISA | Mercodia AB, Uppsala Sweden | 10-1132-01, 10-1134-01 | |
| Plate reader | Tecan infinite F200 pro, Männedorf, Switzerland | ||
| Name | Company | Catalog Number | Comments |
| Further equipment | |||
| Measures of fat-free-mass | FFM-Tanita T5896, Tanita, Tokyo, Japan | ||
| Strength training equipment for all training exercises | Cybex International Inc., Medway, Massachusetts, USA | ||
| Cycle ergometer | Monark Ergometer 893E, Monark Exercises, Varberg, Sweden | ||
| Heart rate monitor RS800, Polar | Polar Electro OY, Kampele, Finland | ||
| Oxycin-Pro – automatic ergo-spirometric device | Erich Jaeger GmbH, Hoechberg, Germany | ||
| Isokinetic dynamometer, Isomed 2000, knee muscle strength | D&R Ferstl GmbH, Henau, Germany | ||
| CED 1401 data acquisition system and Signal software | Cambridge Electronic Design, Cambridge, UK | ||
| Software for muscle strength analysis, Spike 2, version 7 | Signal Hound, LA Center, WA, USA | ||
| Statistica software for statistical analyses | Statistica, Stat soft. inc, Tulsa, Oklahoma, USA | ||
| Name | Company | Catalog Number | Comments |
| Muscle biopsy equipment | |||
| Weil Blakesley conchotome | Wisex, Mölndal, Sweden | ||
| Local anesthesia | Carbocain, 20 mL, 20 mg/mL; Astra Zeneca, Södertälje, Sweden | 169,367 | |
| Surgical Blade | Feather Safety Razor CO, LTD, Osaka, Japan | 11048030 |
References
- Carrick-Ranson, G., et al. The effect of age-related differences in body size and composition on cardiovascular determinants of VO2max. J. Gerontol. A Biol. Sci. Med. Sci. 68 (5), 608-616 (2013).
- Peterson, C. M., Johannsen, D. L., Ravussin, E. Skeletal muscle mitochondria and aging: a review. J. Aging. 2012, 194821 (2012).
- Russell, A. P., Foletta, V. C., Snow, R. J., Wadley, G. D. Skeletal muscle mitochondria: a major player in exercise, health and disease. Biochim. Biophys. Acta. 1840 (4), 1276-1284 (2014).
- Conley, K. E., Jubrias, S. A., Esselman, P. C. Oxidative capacity and ageing in human muscle. J. Physiol. 526 (Pt 1), 203-210 (2000).
- Holloszy, J. O. Adaptation of skeletal muscle to endurance exercise. Med. Sci. Sports. 7 (3), 155-164 (1975).
- Menshikova, E. V., Ritov, V. B., Fairfull, L., Ferrell, R. E., Kelley, D. E., Goodpaster, B. H. Effects of exercise on mitochondrial content and function in aging human skeletal muscle. J. Gerontol. A Biol. Sci. Med. Sci. 61 (6), 534-540 (2006).
- Balakrishnan, V. S., et al. Resistance training increases muscle mitochondrial biogenesis in patients with chronic kidney disease. Clin. J. Am. Soc. Nephrol. 5 (6), 996-1002 (2010).
- Ferrara, C. M., Goldberg, A. P., Ortmeyer, H. K., Ryan, A. S. Effects of aerobic and resistive exercise training on glucose disposal and skeletal muscle metabolism in older men. J. Gerontol. A Biol. Sci. Med. Sci. 61 (5), 480-487 (2006).
- Frontera, W. R., Meredith, C. N., O’Reilly, K. P., Evans, W. J. Strength training and determinants of VO2max in older men. J. Appl. Physiol. (1985). 68 (1), 329-333 (1990).
- Toth, M. J., Miller, M. S., Ward, K. A., Ades, P. A. Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training. J. Appl. Physiol. (1985). 112 (11), 1864-1874 (2012).
- Zachwieja, J. J., Toffolo, G., Cobelli, C., Bier, D. M., Yarasheski, K. E. Resistance exercise and growth hormone administration in older men: effects on insulin sensitivity and secretion during a stable-label intravenous glucose tolerance test. Metabolism. 45 (2), 254-260 (1996).
- Davidson, L. E., et al. Effects of exercise modality on insulin resistance and functional limitation in older adults: a randomized controlled trial. Arch. Intern. Med. 169 (2), 122-131 (2009).
- DeFronzo, R. A., Tobin, J. D., Andres, R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am. J. Physiol. 237 (3), E214-E223 (1979).
- Åstrand, P. O., Ryhming, I. A nomogram for calculation of aerobic capacity (physical fitness) from pulse rate during sub-maximal work. J. Appl. Physiol. 7 (2), 218-221 (1954).
- Björkman, F., Ekblom-Bak, E., Ekblom, &. #. 2. 1. 4. ;., Ekblom, B. Validity of the revised Ekblom Bak cycle ergometer test in adults. Eur. J. Appl. Physiol. 116 (9), 1627-1638 (2016).
- Seger, J. H., Westing, S. H., Hanson, M., Karlson, E., Ekblom, B. A new dynamometer measuring eccentric and eccentric muscle strength in accelerated, decelerated and isokinetic movements: validity and reproducibility. Eur. J. Appl. Physiol. 57 (5), 526-530 (1988).
- Westing, S. H., Seger, J. Y., Karlson, E., Ekblom, B. Eccentric and concentric torque-velocity characteristics of the quadriceps femoris in man. Eur. J. Appl. Physiol. 58 (1-2), 100-104 (1988).
- Aagaard, P., Simonsen, E. B., Andersen, J. L., Magnusson, P., Dyhre-Poulsen, P. Increased rate of force development and neural drive of human skeletal muscle following resistance training. J. Appl. Physiol. 93 (4), 1318-1326 (2002).
- Andersen, L. L., Aagaard, P. Influence of maximal muscle strength and intrinsic muscle contractile properties on contractile rate of force development. Eur. J. Appl. Physiol. 96 (1), 46-52 (2006).
- Henriksson, K. G. “Semi-open” muscle biopsy technique. A simple outpatient procedure. Acta Neurol. Scand. 59 (6), 317-323 (1979).
- Matsuda, M., DeFronzo, R. A. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 22 (9), 1462-1470 (1999).
- American Diabetes, Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 28, S37-S42 (2005).
- Moberg, M., Apró, W., Ekblom, B., van Hall, G., Holmberg, H. C., Blomstrand, E. Activation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise. Am. J. Physiol. Cell Physiol. 310 (11), C874-C884 (2016).
- Antharavally, B. S., Carter, B., Bell, P. A., Krishna Mallia, ., A, A high-affinity reversible protein stain for Western blots. Anal. Biochem. 329 (2), 276-280 (2004).
- Brooke, M. H., Kaiser KK, . Muscle fiber types: how many and what kind?. Arch. Neurol. 23 (4), 369-379 (1970).
- Brooke, M. H., Kaiser, K. K. Three "myosin adenosine triphosphatase" systems: the nature of their pH lability and sulfhydryl dependence. J. Histochem. Cytochem. 18 (9), 670-672 (1970).
- Andersen, P. Capillary density in skeletal muscle of man. Acta Physiol. Scand. 95 (2), 203-205 (1975).
- Frank, P., Andersson, E., Pontén, M., Ekblom, B., Ekblom, M., Sahlin, K. Strength training improves muscle aerobic capacity and glucose tolerance in elderly. Scand. J. Med. Sci. Sports. 26 (7), 764-773 (2016).
- Blomstrand, E., Celsing, F., Fridén, J., Ekblom, B. How to calculate human muscle fibre areas in biopsy samples–methodological considerations. Acta Physiol. Scand. 122 (4), 545-551 (1984).
- Cuthbertson, D., et al. Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J. 19 (3), 422-424 (2005).
- Vincent, K. R., Braith, R. W., Feldman, R. A., Kallas, H. E., Lowenthal, D. T. Improved cardiorespiratory endurance following 6 months of resistance exercise in elderly men and women. Arch. Intern. Med. 162 (6), 673-678 (2002).
- Cadore, E. L., et al. Effects of strength, endurance, and concurrent training on aerobic power and dynamic neuromuscular economy in elderly men. J. Strength Cond. Res. 25 (3), 758-766 (2011).
- Jubrias, S. A., Esselman, P. C., Price, L. B., Cress, M. E., Conley, K. E. Large energetic adaptations of elderly muscle to resistance and endurance training. J. Appl. Physiol. (1985). 90 (5), 1663-1670 (1985).
- Benton, C. R., Wright, D. C., Bonen, A. PGC-1alpha-mediated regulation of gene expression and metabolism: implications for nutrition and exercise prescriptions. Appl. Physiol. Nutr. Metab. 33 (5), 843-862 (2008).
