Regular Multicomponent Exercise Increases Physical Fitness and Muscle Protein Anabolism in Frail, Obese, Older Adults

Villareal, Dennis T.; Smith, Gordon I.; Sinacore, David R.; Shah, Krupa; Mittendorfer, Bettina

doi:10.1038/oby.2010.110

Cited by 140Muscle metabolism and nutritionNutrition and Health in AgingCardiovascular and exercise physiology

Regular Multicomponent Exercise Increases Physical Fitness and Muscle Protein Anabolism in Frail, Obese, Older Adults

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Villareal, Dennis T., Smith, Gordon I., Sinacore, David R., Shah, Krupa, Mittendorfer, Bettina·2011·Obesity

DOI 10.1038/oby.2010.110PMC PMC3069710

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Abstract

Aging is associated with a decline in strength, endurance, balance, and mobility. Obesity worsens the age‐related impairment in physical function and often leads to frailty. The American College of Sports Medicine recommends a multicomponent (strength, endurance, flexibility, and balance) exercise program to maintain physical fitness. However, the effect of such an exercise program on physical fitness in frail, obese older adults is not known. We therefore determined the effect of a 3‐month long multicomponent exercise training program, on endurance (peak aerobic capacity (VO 2 peak)), muscle strength, muscle mass, and the rate of muscle protein synthesis (basal rate and anabolic response to feeding) in nine 65‐ to 80‐year‐old, moderately frail, obese older adults. After 3 months of training, fat mass decreased (P < 0.05) whereas fat‐free mass (FFM), appendicular lean body mass, strength, and VO 2 peak increased (all P < 0.05). Regular strength and endurance exercise increased the mixed muscle protein fractional synthesis rate (FSR) but had no effect on the feeding‐induced increase in muscle protein FSR (∼0.02%/h increase from basal values both before and after exercise training; effect of feeding: P = 0.02; effect of training: P = 0.047; no interaction: P = 0.84). We conclude that: (i) a multicomponent exercise training program has beneficial effects on muscle mass and physical function and should therefore be recommended to frail, obese older adults, and (ii) regular multicomponent exercise increases the basal rate of muscle protein synthesis without affecting the magnitude of the muscle protein anabolic response to feeding.

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Aerobic exercise, resistance training and their combination raise muscle protein synthesis in older adults despite age-related declines in anabolic signalling.
“Aerobic exercise101, resistance training102–104 and their combination105 increase muscle protein synthesis in older adults despite age-related decreases in anabolic signalling106–109.”
From Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies (2018) · cites this paper as [105]
Chronic calorie restriction does not seem to reduce muscle protein synthesis, but might increase it.
“chronic calorie restriction does not seem to reduce muscle protein synthesis, but it might increase it105,255”
From Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies (2018) · cites this paper as [105]
The Methods (Experimental protocol; page unavailable) say participants were counseled to maintain a weight-maintaining diet, not to restrict calories. The Results (Muscle protein synthesis rate; page unavailable) report increased synthesis after exercise training. The copy therefore does not address whether chronic calorie restriction reduces or increases muscle protein synthesis; I searched for calorie restriction, energy restriction, and weight loss. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Exercise training reduces frailty in older adults by suppressing muscle inflammation and promoting anabolism, thereby increasing muscle protein synthesis rate.
“Exercise training reduces frailty in older adults by suppressing muscle inflammation and promoting anabolism, thereby increasing muscle protein synthesis rate [148,336,337].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [148]
Colleluori et al. showed that 6-month multicomponent training among obese older adults was more effective than aerobic or PRT alone for improving muscle protein synthesis and myocellular quality, even though mitochondrial biogenesis increased the most in the aerobic exercise group.
“In a well-designed RCT, Colleluori et al. [148,336,337] showed that 6-month multicomponent training among obese older adults was more effective than aerobic or PRT alone for improving muscle protein synthesis and myocellular quality, even though mitochondrial biogenesis increased the most in the aerobic exercise group.”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [148]
6-month multicomponent training among obese older adults was more effective than aerobic or PRT alone for improving muscle protein synthesis and myocellular quality, even though mitochondrial biogenesis increased most in the aerobic exercise group.
“In a well-designed RCT, Colleluori et al. [148,336,337] showed that 6-month multicomponent training among obese older adults was more effective than aerobic or PRT alone for improving muscle protein synthesis and myocellular quality, even though mitochondrial biogenesis increased the most in the aerobic exercise group.”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [148]

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Background
Effects of Aerobic Exercise Training in Community‐Based Subjects Aged 80 and Older: A Pilot Study
Vaitkevicius, P. V., Ebersold, C., Shah, M. S., Gill, N. S., Katz, R. L., Narrett, M. J., Applebaum, G. E., Parrish, S. M., O’Connor, F. C., & Fleg, J. L. (2002) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2002.50613.x · Cited by 65 · cited 1× · see citing works
“There is good evidence that resistance training alone (9–11) increases the rate of muscle protein synthesis and muscle mass and strength whereas endurance training alone improves aerobic capacity (12,13) in nonobese older adults.”
Background
THE MUSCLE STRENGTH AND SIZE RESPONSE TO UPPER ARM,UNILATERAL RESISTANCE TRAINING AMONG ADULTS WHO ARE OVERWEIGHT AND OBESE
Pescatello, L. S., Kelsey, B. K., Price, T. B., Seip, R. L., Angelopoulos, T. J., Clarkson, P. M., Gordon, P. M., Moyna, N. M., Visich, P. S., Zoeller, R. F., et al. (2007) · The Journal of Strength and Conditioning Research · doi:10.1519/r-22236.1 · Cited by 42 · cited 2× · see citing works
“In addition, there is some evidence that the resistant exercise–induced increases in muscle mass and strength are blunted in young, obese compared with young, lean individuals (17,18).”
BackgroundMethod
The Association Between Adiposity and the Response to Resistance Training Among Pre- and Early-Pubertal Boys
Falk, B., Sadres, E., Constantini, N., Zigel, L., Lidor, R., & Eliakim, A. (2002) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2002.15.5.597 · Cited by 41 · cited 2× · see citing works
“In addition, there is some evidence that the resistant exercise–induced increases in muscle mass and strength are blunted in young, obese compared with young, lean individuals (17,18).”
BackgroundMethod
Measurement of human mixed muscle protein fractional synthesis rate depends on the choice of amino acid tracer
Smith, G. I., Villareal, D. T., & Mittendorfer, B. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00185.2007 · Cited by 33 · cited 1× · see citing works
“All gas-chromatography/mass-spectrometry analyses were carried out in conjunction with standards of known isotope enrichment (36,38); the following mass-to-charge ratios were monitored: 200 (M+0), 202 (M+2), and 203 (M+3) for leucine and 259 (M+0) and 262 (M+3) KIC.”
MethodSelf-citation
Keto acids in tissues and biological fluids:O-t-butyldimethylsilyl quinoxalinols as derivatives for sensitive gas chromatographic/mass spectrometric determination
Langenbeck, U., Luthe, H., & Schaper, G. (1985) · Journal of Mass Spectrometry · doi:10.1002/bms.1200120912 · Cited by 32 · see citing works
Timing of the initial muscle biopsy does not affect the measured muscle protein fractional synthesis rate during basal, postabsorptive conditions.
Smith, G. I., Villareal, D., Lambert, C., Reeds, D. N., Mohammed, B., & Mittendorfer, B. (2010) · Journal of applied physiology · doi:10.1152/japplphysiol.00957.2009 · Cited by 27 · cited 3× · see citing works
“, the first and second and the second and third, respectively), Eic is the enrichment of the precursor for protein synthesis and t is the time between biopsies (33).”
BackgroundMethodInfluentialSelf-citation

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[40]Smith GI Villareal DT Lambert CP Reeds DN Mohammed BS Mittendorfer B Timing of the initial muscle biopsy does not affect the measured muscle protein fractional synthesis rate during basal, postabsorptive conditions. J Appl Physiol 2009 PMC2822667 19940095

Sorted by citations

Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies
Batsis, J. A., & Villareal, D. T. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0062-9 · Cited by 1,382 · see citing works
Self-citation
Resistance Training for Older Adults: Position Statement From the National Strength and Conditioning Association
Fragala, M. S., Cadore, E. L., Dorgo, S., Izquierdo, M., Kraemer, W. J., Peterson, M. D., & Ryan, E. D. (2019) · Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000003230 · Cited by 1,290 · see citing works
International exercise recommendations in older adults (ICFSR): Expert consensus guidelines
Izquierdo, M., Merchant, R. A., Morley, J. E., Anker, S. D., Aprahamian, I., Arai, H., Aubertin-Leheudre, M., Bernabei, R., Cadore, E. L., Cesari, M., et al. (2021) · The Journal of nutrition, health and aging · doi:10.1007/s12603-021-1665-8 · Cited by 1,247 · see citing works
Self-citation
Effects of different exercise interventions on risk of falls, gait ability, and balance in physically frail older adults: a systematic review
Cadore, E. L., Rodríguez-Mañas, L., Sinclair, A., & Izquierdo, M. (2013) · Rejuvenation Research · doi:10.1089/rej.2012.1397 · Cited by 954 · see citing works
“15,16,26,28 This statement is supported by the literature, in which positive effects on functional capacity are more often observed when more than one physical-conditioning component ( i.e ., strength, endurance, or balance) comprises the exercise intervention, 15,16,26,28 compared with only one…”
Influential
Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials
de Labra, C., Guimaraes-Pinheiro, C., Maseda, A., Lorenzo, T., & Millán-Calentí, J. C. (2015) · BMC Geriatrics · doi:10.1186/s12877-015-0155-4 · Cited by 714 · see citing works
“overall health status of frail elderly people [13, 39], our search strategy focused on studies with a variety of exercise programs and with a broad range of methods to evaluate the results.”
Background
Multicomponent exercises including muscle power training enhance muscle mass, power output, and functional outcomes in institutionalized frail nonagenarians
Cadore, E. L., Casas-Herrero, A., Zambom-Ferraresi, F., Idoate, F., Millor, N., Gómez, M., Rodriguez-Mañas, L., & Izquierdo, M. (2014) · AGE · doi:10.1007/s11357-013-9586-z · Cited by 526 · see citing works
“Indeed, the benefits of physical exercise in improving the functional capacity of frail older adults have been the focus of considerable recent research (Fiatarone et al. 1994; Hauer et al. 2001; Barnett et al. 2003; Lord et al. 2003; Serra-Rexach et al. 2011; Villareal et al. 2011; Clemson et al. 2012; Freiberger et…”
Background
Low-Load High Volume Resistance Exercise Stimulates Muscle Protein Synthesis More Than High-Load Low Volume Resistance Exercise in Young Men
Burd, N. A., West, D. W. D., Staples, A. W., Atherton, P. J., Baker, J. M., Moore, D. R., Holwerda, A. M., Parise, G., Rennie, M. J., Baker, S. K., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012033 · Cited by 531 · see citing works
Exercise Attenuates the Major Hallmarks of Aging
Garatachea, N., Pareja-Galeano, H., Sanchis-Gomar, F., Santos-Lozano, A., Fiuza-Luces, C., Morán, M., Emanuele, E., Joyner, M. J., & Lucia, A. (2015) · Rejuvenation Research · doi:10.1089/rej.2014.1623 · Cited by 413 · see citing works
“studied the effect of such a multicomponent exercise program on physical fitness in frail, obese older adults during 3 months, finding beneficial effects on muscle mass and physical function.(96) Lord et al.”
Background
Enhanced Amino Acid Sensitivity of Myofibrillar Protein Synthesis Persists for up to 24 h after Resistance Exercise in Young Men1–3
Burd, N. A., West, D. W. D., Moore, D. R., Atherton, P. J., Staples, A. W., Prior, T., Tang, J. E., Rennie, M. J., Baker, S. K., & Phillips, S. M. (2011) · The Journal of Nutrition · doi:10.3945/jn.110.135038 · Cited by 325 · see citing works
Strength and Endurance Training Prescription in Healthy and Frail Elderly
Cadore, E. L. (2014) · Aging and Disease · doi:10.14336/ad.2014.0500183 · Cited by 273 · see citing works
“Endurance training for frail individuals should include walking with changes in pace and direction [4244,46,87], treadmill walking [43,86], step-ups, stair climbing, and stationary cycling [43,46].”
Background
Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR)
Izquierdo, M., de Souto Barreto, P., Arai, H., Bischoff-Ferrari, H. A., Cadore, E. L., Cesari, M., Chen, L.-K., Coen, P. M., Courneya, K. S., Duque, G., et al. (2025) · The Journal of nutrition, health and aging · doi:10.1016/j.jnha.2024.100401 · Cited by 273 · see citing works
Self-citation
Obesity and the Elderly
Mathus-Vliegen, E. M. H. (2012) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e31825692ce · Cited by 222 · see citing works
Role of physical exercise on cognitive function in healthy older adults: A systematic review of randomized clinical trials
Sáez de Asteasu, M. L., Martínez-Velilla, N., Zambom-Ferraresi, F., Casas-Herrero, Á., & Izquierdo, M. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.05.007 · Cited by 215 · see citing works
Health benefits of multicomponent training programmes in seniors: a systematic review
Bouaziz, W., Lang, P. O., Schmitt, E., Kaltenbach, G., Gény, B., & Vogel, T. (2016) · International Journal of Clinical Practice · doi:10.1111/ijcp.12822 · Cited by 213 · see citing works
Prevalence, Pathophysiology, Health Consequences and Treatment Options of Obesity in the Elderly: A Guideline
Mathus-Vliegen, E. M. H., Basdevant, A., Finer, N., Hainer, V., Hauner, H., Micic, D., Maislos, M., Roman, G., Schutz, Y., Tsigos, C., et al. (2012) · Obesity Facts · doi:10.1159/000341193 · Cited by 261 · see citing works
Aging, obesity, sarcopenia and the effect of diet and exercise intervention
Colleluori, G., & Villareal, D. T. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111561 · Cited by 207 · see citing works
Self-citation
Obesity and Physical Frailty in Older Adults: A Scoping Review of Lifestyle Intervention Trials
Starr, K. N. P., McDonald, S. R., & Bales, C. W. (2014) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2013.11.008 · Cited by 189 · see citing works
The Frailty Syndrome: A Comprehensive Review
Heuberger, R. (2011) · Journal of Nutrition in Gerontology and Geriatrics · doi:10.1080/21551197.2011.623931 · Cited by 187 · see citing works
Physical Exercise as Therapy for Frailty
Aguirre, L. E., & Villareal, D. T. (2015) · Nestlé Nutrition Institute Workshop series · doi:10.1159/000382065 · Cited by 174 · see citing works
Self-citation
Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip bone mineral density induced by weight loss despite decline in bone-active hormones
Shah, K., Armamento-Villareal, R., Parimi, N., Chode, S., Sinacore, D. R., Hilton, T. N., Napoli, N., Qualls, C., & Villareal, D. T. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.475 · Cited by 173 · see citing works
“It remains unclear whether the aggregate benefits of weight loss and ET on physical function((4,48)) could lower the risk of falls and fractures despite the decline in hip BMD.”
BackgroundSelf-citation
Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women
Markofski, M., Dickinson, J., Drummond, M., Fry, C., Fujita, S., Gundermann, D., Glynn, E., Jennings, K., Paddon-Jones, D., Reidy, P., et al. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.02.015 · Cited by 155 · see citing works
“While the subjects were obese and lost fat mass with training, that study demonstrates how exercise can affect basal muscle protein synthesis in older adults (Villareal et al., 2011).”
Sarcopenic obesity: molecular clues to a better understanding of its pathogenesis?
Kob, R., Bollheimer, L. C., Bertsch, T., Fellner, C., Djukic, M., Sieber, C. C., & Fischer, B. E. (2015) · Biogerontology · doi:10.1007/s10522-014-9539-7 · Cited by 151 · see citing works
“…et al. 2007), increased mitochondrial function (Lanza and Nair 2009), decreased circulating myostatin (Argiles et al. 2012), upregulated muscle protein synthesis (Villareal et al. 2011) and enhancement of nutrient stimulated vasodilatation and nutrient delivery to muscle (Timmerman et al. 2012).”
Influential
Sarcopenic obesity: how do we treat it?
Bouchonville, M. F., & Villareal, D. T. (2013) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/01.med.0000433071.11466.7f · Cited by 141 · see citing works
Self-citation
Aerobic plus resistance exercise in obese older adults improves muscle protein synthesis and preserves myocellular quality despite weight loss
Colleluori, G., Aguirre, L., Phadnis, U., Fowler, K., Armamento-Villareal, R., Sun, Z., Brunetti, L., Hyoung Park, J., Kaipparettu, B. A., Putluri, N., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.06.008 · Cited by 135 · see citing works
Self-citation
Usefulness of combining intermittent hypoxia and physical exercise in the treatment of obesity
Urdampilleta, A., González‐Muniesa, P., Portillo, M. P., & Martínez, J. A. (2011) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-011-0115-1 · Cited by 123 · see citing works
The Effect of Physiological Stimuli on Sarcopenia; Impact of Notch and Wnt Signaling on Impaired Aged Skeletal Muscle Repair
Arthur, S. T., & Cooley, I. D. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.4262 · Cited by 119 · see citing works
“Protein synthesis/degradation balance: Physiological stimuli consisting of a variety of exercise modes may be a form of treatment that can counteract the protein imbalance in aging skeletal muscle (77, 93, 248-255).”
Background
Multicomponent exercise and the hallmarks of frailty: Considerations on cognitive impairment and acute hospitalization
Cadore, E. L., Sáez de Asteasu, M. L., & Izquierdo, M. (2019) · Experimental Gerontology · doi:10.1016/j.exger.2019.04.007 · Cited by 112 · see citing works
The Molecular Basis for Load-Induced Skeletal Muscle Hypertrophy
Marcotte, G. R., West, D. W. D., & Baar, K. (2014) · Calcified Tissue International · doi:10.1007/s00223-014-9925-9 · Cited by 108 · see citing works
“Despite its wide-ranging benefits [22], resistance training is under-prescribed [23] and regularly practiced only by a small minority of individuals.”
Background
Effect of a multicomponent exercise programme (VIVIFRAIL) on functional capacity in frail community elders with cognitive decline: study protocol for a randomized multicentre control trial
Herrero, Á. C., Antón‐Rodrigo, I., Zambom-Ferraresi, F., de Asteasu, M. L. S., Martínez‐Velilla, N., Elexpuru‐Estomba, J., Marín‐Epelde, I., Ramón‐Espinoza, F., Torregrosa, R. P., Sánchez‐Sánchez, J. L., et al. (2019) · Trials · doi:10.1186/s13063-019-3426-0 · Cited by 111 · see citing works
Functional capacity, muscle fat infiltration, power output, and cognitive impairment in institutionalized frail oldest old
Casas-Herrero, A., Cadore, E. L., Zambom-Ferraresi, F., Idoate, F., Millor, N., Martínez-Ramirez, A., Gómez, M., Rodriguez-Mañas, L., Marcellán, T., de Gordoa, A. R., et al. (2013) · Rejuvenation Research · doi:10.1089/rej.2013.1438 · Cited by 105 · see citing works
Effects of Kinect-based exergaming on frailty status and physical performance in prefrail and frail elderly: A randomized controlled trial
Liao, Y.-Y., Chen, I.-H., & Wang, R. (2019) · Scientific Reports · doi:10.1038/s41598-019-45767-y · Cited by 101 · see citing works
Anabolic sensitivity of postprandial muscle protein synthesis to the ingestion of a protein-dense food is reduced in overweight and obese young adults
Beals, J. W., Sukiennik, R. A., Nallabelli, J., Emmons, R. S., van Vliet, S., Young, J. R., Ulanov, A. V., Li, Z., Paluska, S. A., De Lisio, M., et al. (2016) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.116.130385 · Cited by 99 · see citing works
Effect of Aerobic or Resistance Exercise, or Both, on Intermuscular and Visceral Fat and Physical and Metabolic Function in Older Adults With Obesity While Dieting
Waters, D. L., Aguirre, L., Gurney, B., Sinacore, D. R., Fowler, K., Gregori, G., Armamento-Villareal, R., Qualls, C., & Villareal, D. T. (2022) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glab111 · Cited by 99 · see citing works
“Indeed, we have recently reported that the combination of aerobic and resistance exercise in this study population was superior to either mode independently for improving MPS and myocellular quality, thereby maintaining muscle mass during weight loss therapy, which was accompanied by preservation of myocyte-enhancing…”
BackgroundSelf-citation
Excessive Body Weight in Older Adults
Starr, K. N. P., & Bales, C. W. (2015) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2015.04.001 · Cited by 90 · see citing works
Obesity Alters the Muscle Protein Synthetic Response to Nutrition and Exercise
Beals, J. W., Burd, N. A., Moore, D. R., & van Vliet, S. (2019) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00087 · Cited by 88 · see citing works
“Two reports showed that increased multimodality physical activity (endurance + resistance) over a 3 month period increases basal mixed muscle protein synthesis rates, but the magnitude of postprandial stimulation of muscle protein synthesis rates was not affected (140).”
Background
Western-style diet, sex steroids and metabolism
Varlamov, O. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.05.025 · Cited by 89 · see citing works
Effects of a 12-Week Exercise Training Program on Physical Function in Institutionalized Frail Elderly
Ferreira, C. B., Teixeira, P. D. S., dos Santos, G. A., Maya, Á. T. D., do Brasil, P. A., Souza, V. C., Córdova, C., Ferreira, A. P., Lima, R. M., & Nóbrega, O. D. T. (2018) · Journal of Aging Research · doi:10.1155/2018/7218102 · Cited by 86 · see citing works
. A new frailty syndrome: central obesity and frailty in older adults with the human immunodeficiency virus.
Shah, K., Hilton, T. N., Myers, L., Pinto, J. F., Luque, A. E., & Hall, W. J. (2012) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2011.03819.x · Cited by 77 · see citing works
Self-citation
Multicomponent exercise for physical fitness of community-dwelling elderly women
Kang, S.-H., Hwang, S., Klein, A. B., & Kim, S. H. (2015) · Journal of Physical Therapy Science · doi:10.1589/jpts.27.911 · Cited by 76 · see citing works
Effects of multicomponent exercise on frailty status and physical function in frail older adults: A meta-analysis and systematic review
Yang, X., Li, S., Xu, L., Liu, H., Li, Y., Song, X., Bao, J., Liao, S., Xi, Y., & Guo, G. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112604 · Cited by 66 · see citing works
Validation of a single biopsy approach and bolus protein feeding to determine myofibrillar protein synthesis in stable isotope tracer studies in humans
Burd, N. A., West, D. W. D., Rerecich, T., Prior, T., Baker, S. K., & Phillips, S. M. (2011) · Nutrition & Metabolism · doi:10.1186/1743-7075-8-15 · Cited by 66 · see citing works
“Our laboratory [4,6,8,10] and others [11-17] have a long standing interest in determining the FSR of muscle proteins after different acute exercise and feeding interventions.”
Background
Muscle Protein Synthesis Response to Exercise Training in Obese, Older Men and Women
Smith, G. I., Villareal, D. T., Sinacore, D. R., Shah, K. N., & Mittendorfer, B. (2012) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3182496a41 · Cited by 65 · see citing works
“The net muscle protein anabolic response to a meal is therefore largely determined by the amount of protein ingested and is greater during meal intake/hyperaminoacidemia after exercise than rest (3, 7, 41, 45).”
BackgroundResultSelf-citation
El ejercicio físico en el anciano frágil: una actualización
Herrero, Á. C., Cadore, E. L., Martínez‐Velilla, N., & Izquierdo, M. (2015) · Revista Española de Geriatría y Gerontología · doi:10.1016/j.regg.2014.07.003 · Cited by 63 · see citing works
Training with a balance exercise assist robot is more effective than conventional training for frail older adults
Ozaki, K., Kondo, I., Hirano, S., Kagaya, H., Saitoh, E., Osawa, A., & Fujinori, Y. (2017) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.13009 · Cited by 61 · see citing works
Nutrient-rich, high-quality, protein-containing dairy foods in combination with exercise in aging persons to mitigate sarcopenia
Phillips, S. M., & Martinson, W. (2018) · Nutrition reviews · doi:10.1093/nutrit/nuy062 · Cited by 64 · see citing works
Effects of Mindfulness-Based Tai Chi Chuan on Physical Performance and Cognitive Function among Cognitive Frailty Older Adults: A Six-Month Follow-Up of a Randomized Controlled Trial
Jiayuan, Z., Xiang-Zi, J., Li-Na, M., Jin-Wei, Y., & Xue, Y. (2021) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2021.40 · Cited by 53 · see citing works
Habituation to low or high protein intake does not modulate basal or postprandial muscle protein synthesis rates: a randomized trial
Gorissen, S. H., Horstman, A. M., Franssen, R., Kouw, I. W., Wall, B. T., Burd, N. A., de Groot, L. C., & van Loon, L. J. (2017) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.115.129924 · Cited by 53 · see citing works
Effectiveness of combined exercise training to improve functional fitness in older adults: A randomized controlled trial
Sousa, N., Mendes, R., Abrantes, C. G., Sampaio, J. E., & de Oliveira, J. J. F. (2014) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.12188 · Cited by 51 · see citing works
Effect of weight loss on the rate of muscle protein synthesis during fasted and fed conditions in obese older adults
Villareal, D. T., Smith, G. I., Shah, K., & Mittendorfer, B. (2012) · Obesity · doi:10.1038/oby.2011.280 · Cited by 49 · see citing works
“At 210 min after the start of the leucine tracer infusion, a second muscle biopsy was obtained to determine the basal rate of muscle protein synthesis (as incorporation of [5,5,5-(2)H3]leucine into muscle protein) as previously described (10,11).”
MethodSelf-citation
Effects of concurrent aerobic and resistance exercise in frail and pre-frail older adults
Meng, N., Li, C., Liu, C.-S., Lin, C., Chang, C.-K., Chang, H.-W., Yang, C., Li, T., & Lin, C. (2020) · Medicine · doi:10.1097/md.0000000000021187 · Cited by 41 · see citing works
Effectiveness of the PROMUFRA program in pre-frail, community-dwelling older people: A randomized controlled trial
Barrachina-Igual, J., Martínez‐Arnau, F. M., Pérez‐Ros, P., Flor-Rufino, C., Sanz‐Requena, R., & Pablos, A. (2020) · Geriatric Nursing · doi:10.1016/j.gerinurse.2020.10.014 · Cited by 41 · see citing works
Muscle protein metabolism responds similarly to exogenous amino acids in healthy younger and older adults during NO-induced hyperemia
Dillon, E. L., Casperson, S. L., Durham, W. J., Randolph, K. M., Urban, R. J., Volpi, E., Ahmad, M., Kinsky, M. P., & Sheffield‐Moore, M. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00211.2011 · Cited by 41 · see citing works
“In recent years, considerable scientific attention has focused on the age-associated metabolic responses to a myriad of combinations of exercise and nutrition (7, 9, 19, 21, 34).”
Background
Appendicular lean mass and mortality among prefrail and frail older adults
Brown, J. C., Harhay, M. O., & Harhay, M. O. (2016) · The journal of nutrition health & aging · doi:10.1007/s12603-016-0753-7 · Cited by 39 · see citing works
“and ALM among obese frail older adults (20).”
Background
Physical Exercise Improves Function in Acutely Hospitalized Older Patients: Secondary Analysis of a Randomized Clinical Trial
de Asteasu, M. L. S., Martínez‐Velilla, N., Zambom-Ferraresi, F., Herrero, Á. C., Lucía, A., Galbete, A., & Izquierdo, M. (2019) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2019.04.001 · Cited by 39 · see citing works
Benefits of a multicomponent Falls Unit-based exercise program in older adults with falls in real life
Molina, R. G., Ruiz-Grao, M. C., Noguerón‐García, A., Martínez-Reig, M., Víctor, M. E., Izquierdo, M., & Abizanda, P. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.05.013 · Cited by 39 · see citing works
“Different exercise modalities such as strength, balance, cardiovascular and coordination, have demonstrated functional benefits in frail older adults, although multicomponent exercise programs that specifically include strength and power, endurance and balance training present a better profile (Barnett et al., 2003; L…”
Effect of Training-Detraining Phases of Multicomponent Exercises and BCAA Supplementation on Inflammatory Markers and Albumin Levels in Frail Older Persons
Caldo‐Silva, A., Furtado, G. E., Chupel, M. U., Bachi, A. L. L., Barros, M. P., Neves, R. S., Marzetti, E., Massart, A. G. M., & Teixeira, A. M. (2021) · Nutrients · doi:10.3390/nu13041106 · Cited by 37 · see citing works
“Multicomponent programs combine aerobic and strength exercises, including other physical skills, such as balance and flexibility [54], in order to optimize the functional capacity of frail older persons [72], as well as to maintain their independence to perform basic activities of daily living [73].”
Background
Effects of Combined Balance and Strength Training on Measures of Balance and Muscle Strength in Older Women With a History of Falls
Zouita, S., Zouhal, H., Ferchichi, H., Paillard, T., Dziri, C., Hackney, A. C., Laher, I., Granacher, U., & Zouita, A. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.619016 · Cited by 38 · see citing works
“Our results suggest improvements in static balance allows visual feedback to reduce fall risk in older adults (Villareal et al., 2011).”
Result
Implication of diet and exercise on the management of age‐related sarcopenic obesity in Asians
Kim, Y. J., Moon, S., Yu, J. M., & Chung, H. S. (2022) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.14442 · Cited by 33 · see citing works
Effects of 6-Month Multimodal Physical Exercise Program on Bone Mineral Density, Fall Risk, Balance, and Gait in Patients with Alzheimer’s Disease: A Controlled Clinical Trial
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Basal and Postprandial Myofibrillar Protein Synthesis Rates Do Not Differ between Lean and Obese Middle-Aged Men
Kouw, I. W. K., van Dijk, J., Horstman, A. M. H., Kramer, I. F., Goessens, J. P. B., van Dielen, F. M. H., Verdijk, L. B., & van Loon, L. J. C. (2019) · Journal of Nutrition · doi:10.1093/jn/nxz104 · Cited by 28 · see citing works
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Preventing metabolic syndrome in morbid obesity with resistance training: Reporting interindividual variability
Delgado‐Floody, P., Álvarez, C., Cadore, E. L., Flores‐Opazo, M., Navarrete, F. C., & Izquierdo, M. (2019) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2019.07.002 · Cited by 22 · see citing works
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Predicting physical functioning status in older adults: insights from wrist accelerometer sensors and derived digital biomarkers of physical activity
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“Examples of articles excluded are those in which the intervention was administered from locations such as clinical research units (7), human performance laboratories (9), clinical centers (13), outpatient clinics (2), university medical centers (16,37), biomedical research centers (21), university research centers (24…”
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“Yearlong studies of high-intensity resistance training have shown an increase or maintenance of BMD in postmenopausal women (Villareal et al., 2011).”
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Medical and psychosocial barriers to weight management in older veterans with and without serious mental illness.
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BackgroundResult
Exercise, Exerkines, and Sarcopenia
Chung, H. S., & Choi, K. M. (2026) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2025.0972 · Cited by 12 · see citing works
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Effect of aerobic or resistance exercise, or both on insulin secretion, ciliary neurotrophic factor, and insulin-like growth factor-1 in dieting older adults with obesity
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Self-citation
Short and medium-term effects of a multicomponent physical exercise program with a Mediterranean diet on bone mineral density, gait, balance, and fall risk for patients with Alzheimer disease
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Background
Effects of physical training on functional, clinical, morphological, behavioural and psychosocial outcomes in post-COVID-19 infection: COVID-19 and REhabilitation study (CORE-study)—a study protocol for a randomised controlled clinical trial
Delevatti, R. S., Danielevicz, A., Sirydakis, M. E. D. M., de Melo, P. U. G., Freitas, C. D. L. R., Rech, C. R., Guglielmo, L. G. A., Speretta, G. F. F., Hansen, F., Fonseca, F. R., et al. (2023) · Trials · doi:10.1186/s13063-022-07055-5 · Cited by 11 · see citing works
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“The major findings of this study are as follows: (1) The multicomponent exercise training improved the muscle performance irrespective of age.”
MethodResult
Effects of a Multicomponent Exercise Program, a Detraining Period and Dietary Intake Prediction of Body Composition of Frail and Pre-Frail Older Adults from the EXERNET Elder 3.0 Study
Moradell, A., Navarrete‐Villanueva, D., Fernández‐García, Á. I., Sagarra‐Romero, L., Marín-Puyalto, J., Pérez‐Gómez, J., Gesteiro, E., Ara, I., Casajús, J. A., Gómez‐Cabello, A., et al. (2020) · Sustainability · doi:10.3390/su12239894 · Cited by 7 · see citing works
“Specifically, changes observed with these techniques were in appendicular lean mass [28], cross sectional muscle area and muscle fat-infiltration [30,33].”
Background
「高齢者肥満症診療ガイドライン2018」
日本老年医学会「高齢者の生活習慣病管理ガイドライン」作成ワーキング (2018) · Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics · doi:10.3143/geriatrics.55.464 · Cited by 7 · see citing works
Comparative study of anthropometric and body composition variables, and functionality between elderly that perform regular or irregular physical activity
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“While our analysis did not account for activity type, previous literature suggests that multicomponent physical activity—including strength, endurance, and balance training—may be particularly beneficial for older adults in maintaining physical function and delaying age-related decline 37,38 .”
Resistance Exercise to Mitigate Cancer Cachexia: Molecular Mechanisms and Practical Applications
Lambert, C. P. (2022) · Journal of Cancer Therapy · doi:10.4236/jct.2022.138044 · Cited by 5 · see citing works
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Background
Sarcopenic Obesity
Zamboni, M. M., Macchi, F., Nori, N., & Rossi, A. P. (2021) · doi:10.1002/9781119597896.ch12 · Cited by 5 · see citing works
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A comparison of the aerobic cost and muscle use in aerobic dance to the energy costs and muscle use on treadmill, elliptical trainer and bicycle ergometry
PETROFSKY, J. S., Laymon, M. S., Mcgrew, R., Papa, D. C. R., Hahn, R. L., Kaethler, R., Johnson, M. J., Wernow, B., & Poblete, D. (2013) · Physical therapy rehabilitation science · Cited by 4 · see citing works
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Relationship Between Regular Exercise and Quality of Life Among Middle-Aged and Older Adults in Japan
Yu, D., Shimura, M., & Kawanishi, M. (2025) · Behavioral Sciences · doi:10.3390/bs15070978 · Cited by 3 · see citing works
“This study provides a scientific basis for optimizing the exercise methods and their intensity in the middle-aged and older adults population, highlighting the importance of routine physical exercise in this population (Villareal et al., 2011).”
Exercise Testing and Training Strategies for Healthy and Frail Elderly
Symons, T. B., & Swank, A. M. (2015) · ACSMʼs Health & Fitness Journal · doi:10.1249/fit.0000000000000104 · Cited by 3 · see citing works
“Aerobic exercise in frail older adults should incorporate activities such as walking, with emphasis placed on changes in pace, directional transitions (12,15), treadmill walking (20), step-ups, stair climbing, and stationary cycling (6,20).”
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Can Muscle Mass Be Maintained with A Simple Resistance Intervention in the Older People? A Cluster Randomized Controlled Trial in Thailand
Saengrut, B., Yoda, T., Kimura, Y., Ishimoto, Y., Rattanasathien, R., Saito, T., Chunjai, K., Miyamoto, K., Sirimuengmoon, K., Pudwan, R., et al. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19010140 · Cited by 3 · see citing works
The Impact of Dual-Task Training Versus Single-Task Training on Cognitive and Physical Function in Neurologically Impaired Individuals: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
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“Furthermore, extended periods of physical training induce physiological adaptations, such as increased muscle strength, cardiovascular endurance, and improved metabolic ef ﬁ ciency (Toktarbay et al., 2023; Villareal et al., 2011).”
The physiology of age-related and lifestyle-related decline
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¿En qué personas mayores, dónde y cómo se está aplicando el ejercicio multicomponente para obtener beneficios en su salud? Una revisión sistemática
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Authors: Villareal, D. T., Smith, G. I., Sinacore, D. R., Shah, K., & Mittendorfer, B.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Villareal, Dennis T.
Mittendorfer, Bettina
ORCID: Villareal, Dennis T.
Smith, Gordon I.
Sinacore, David R.
Shah, Krupa
Mittendorfer, Bettina
Venue: Obesity
Publisher: Wiley
Published: 2011-02
Volume: 19
Issue: 2
Pages: 312-318
ISSN: 1930-7381 (ISSN-L)
1930-739X
DOI: 10.1038/oby.2010.110
PMC: PMC3069710
OpenAlex: W2154255635
Cited by: 140
References: 58
Citations by year: 2026: 5 · 2025: 6 · 2024: 11 · 2023: 8 · 2022: 11 · 2021: 15 · 2020: 10 · 2019: 10 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 9 · 2014: 10 · 2013: 8 · 2012: 6
FWCI: 3.22
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 583 d)
Locations: Obesity (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Ellison Medical Foundation
Longer Life Foundation
National Institutes of Health (5p41rr000954-34, UL1TR000448, 7r01ag025501-06, DK56341, RR-00954)
National Institute on Aging (R01-AG025501, K07AG021164, AG 021164, R01AG031176, AG-025501)
National Institute of General Medical Sciences (P41GM103422)
National Institute of Diabetes and Digestive and Kidney Diseases (DK56341, P30DK056341)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR049869, AR 049869)
National Center for Research Resources (P41-RR000954, RR 00954, RR.00036, M01RR000036)
National Center for Advancing Translational Sciences
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords: multicomponent exercise training, frailty, older adults, physical fitness, muscle protein synthesis, muscle protein anabolism, fat-free mass, muscle strength, cardiorespiratory fitness
MeSH terms: Aged, Aged, 80 and over, Aging, Body Composition, Female, Humans, Male, Muscle Proteins, Obesity, Oxygen Consumption, Physical Endurance, Physical Fitness, Exercise, Frail Elderly, Resistance Training

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Regular Multicomponent Exercise Increases Physical Fitness and Muscle Protein Anabolism in Frail, Obese, Older Adults

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