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Physical activity and exercise as countermeasures to physical frailty and sarcopenia


The identification of cost-effective interventions that improve the health status and prevent disability in old age is one of the most important public health challenges. Regular physical activity is the only intervention that has consistently been shown to improve functional health and energy balance and to reduce the risk of cardiovascular disease, stroke, diabetes, several cancers, depression and falls. In advanced age, physical activity is also effective at mitigating sarcopenia, restoring robustness, and preventing/delaying the development of disability. On the other hand, physical inactivity is recognized as one of the leading causes of several chronic degenerative diseases and is also a major contributing factor to sarcopenia and functional disability. This compelling evidence has prompted the World Health Organization to recommend engaging in regular physical activity throughout one’s life course. The present review summarizes the available evidence in support of physical activity as a remedy against physical frailty and sarcopenia. The relevant pathways through which the benefits of physical activity are conveyed are also discussed.

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  1. 1.

    Landi F, Marzetti E, Martone AM, Bernabei R, Onder G (2014) Exercise as a remedy for sarcopenia. Curr Opin Clin Nutr Metab Care 17:25–31. doi:10.1097/MCO.0000000000000018

    PubMed  Google Scholar 

  2. 2.

    Thornell LE (2011) Sarcopenic obesity: satellite cells in the aging muscle. Curr Opin Clin Nutr Metab Care 14:22–27. doi:10.1097/MCO.0b013e3283412260

    Article  PubMed  Google Scholar 

  3. 3.

    Kang JS, Krauss RS (2010) Muscle stem cells in developmental and regenerative myogenesis. Curr Opin Clin Nutr Metab Care 13:243–248. doi:10.1097/MCO.0b013e328336ea98

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Calvani R, Joseph AM, Adhihetty PJ, Miccheli A, Bossola M, Leeuwenburgh C, Bernabei R, Marzetti E (2013) Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy. Biol Chem 394:393–414. doi:10.1515/hsz-2012-0247

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Marzetti E, Lawler JM, Hiona A, Manini T, Seo AY, Leeuwenburgh C (2008) Modulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle. Free Radic Biol Med 44:160–168. doi:10.1016/j.freeradbiomed.2007.05.028

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Rowe GC, Safdar A, Arany Z (2014) Running forward: new frontiers in endurance exercise biology. Circulation 129:798–810. doi:10.1161/CIRCULATIONAHA.113.001590

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Fielding RA, LeBrasseur NK, Cuoco A, Bean J, Mizer K, Fiatarone Singh MA (2002) High-velocity resistance training increases skeletal muscle peak power in older women. J Am Geriatr Soc 50:655–662. doi:10.1046/j.1532-5415.2002.50159.x

    Article  PubMed  Google Scholar 

  8. 8.

    Paillard T, Lafont C, Soulat JM, Costes-Salon MC, Mario B, Montoya R, Dupui P (2004) Neuromuscular effects of three training methods in ageing women. J Sports Med Phys Fitness 44:87–91

    CAS  PubMed  Google Scholar 

  9. 9.

    Suetta C, Andersen JL, Dalgas U, Berget J, Koskinen S, Aagaard P, Magnusson SP, Kjaer M (2008) Resistance training induces qualitative changes in muscle morphology, muscle architecture, and muscle function in elderly postoperative patients. J Appl Physiol (1985) 105:180–186. doi:10.1152/japplphysiol.01354.2007

    Article  Google Scholar 

  10. 10.

    Beyer I, Mets T, Bautmans I (2012) Chronic low-grade inflammation and age-related sarcopenia. Curr Opin Clin Nutr Metab Care 15:12–22. doi:10.1097/MCO.0b013e32834dd297

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Marzetti E, Groban L, Wohlgemuth SE, Lees HA, Lin M, Jobe H, Giovannini S, Leeuwenburgh C, Carter CS (2008) Effects of short-term GH supplementation and treadmill exercise training on physical performance and skeletal muscle apoptosis in old rats. Am J Physiol Regul Integr Comp Physiol 294:R558–R567. doi:10.1152/ajpregu.00620.2007

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Marzetti E, Privitera G, Simili V, Wohlgemuth SE, Aulisa L, Pahor M, Leeuwenburgh C (2010) Multiple pathways to the same end: mechanisms of myonuclear apoptosis in sarcopenia of aging. Sci World J 10:340–349. doi:10.1100/tsw.2010.27

    CAS  Article  Google Scholar 

  13. 13.

    Wohlgemuth SE, Lees HA, Marzetti E, Manini TM, Aranda JM, Daniels MJ, Pahor M, Perri MG, Leeuwenburgh C, Anton SD (2011) An exploratory analysis of the effects of a weight loss plus exercise program on cellular quality control mechanisms in older overweight women. Rejuvenation Res 14:315–324. doi:10.1089/rej.2010.1132

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Marzetti E, Calvani R, Bernabei R, Leeuwenburgh C (2012) Apoptosis in skeletal myocytes: a potential target for interventions against sarcopenia and physical frailty—a mini-review. Gerontology 58:99–106. doi:10.1159/000330064

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Binder EF, Yarasheski KE, Steger-May K, Sinacore DR, Brown M, Schechtman KB, Holloszy JO (2005) Effects of progressive resistance training on body composition in frail older adults: results of a randomized, controlled trial. J Gerontol A Biol Sci Med Sci 60:1425–1431. doi:10.1093/gerona/60.11.1425

    Article  PubMed  Google Scholar 

  16. 16.

    Bonnefoy M, Cornu C, Normand S, Boutitie F, Bugnard F, Rahmani A, Lacour JR, Laville M (2003) The effects of exercise and protein-energy supplements on body composition and muscle function in frail elderly individuals: a long-term controlled randomised study. Br J Nutr 89:731–739. doi:10.1079/BJN2003836

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Bunout D, Barrera G, de la Maza P, Avendano M, Gattas V, Petermann M, Hirsch S (2001) The impact of nutritional supplementation and resistance training on the health functioning of free-living Chilean elders: results of 18 months of follow-up. J Nutr 131:2441 S–2446 S

    CAS  Google Scholar 

  18. 18.

    Goodpaster BH, Chomentowski P, Ward BK, Rossi A, Glynn NW, Delmonico MJ, Kritchevsky SB, Pahor M, Newman AB (2008) Effects of physical activity on strength and skeletal muscle fat infiltration in older adults: a randomized controlled trial. J Appl Physiol (1985) 105:1498–1503. doi:10.1152/japplphysiol.90425.2008

    Article  Google Scholar 

  19. 19.

    Kemmler W, von SS, Engelke K, Haberle L, Mayhew JL, Kalender WA (2010) Exercise, body composition, and functional ability: a randomized controlled trial. Am J Prev Med 38:279–287. doi:10.1016/j.amepre.2009.10.042

    Article  PubMed  Google Scholar 

  20. 20.

    Rydwik E, Lammes E, Frandin K, Akner G (2008) Effects of a physical and nutritional intervention program for frail elderly people over age 75. A randomized controlled pilot treatment trial. Aging Clin Exp Res 20:159–170. doi:10.1007/BF03324763

    Article  PubMed  Google Scholar 

  21. 21.

    Campbell WW, Trappe TA, Jozsi AC, Kruskall LJ, Wolfe RR, Evans WJ (2002) Dietary protein adequacy and lower body versus whole body resistive training in older humans. J Physiol 542:631–642. doi:10.1113/jphysiol.2002.020685

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Marques EA, Mota J, Machado L, Sousa F, Coelho M, Moreira P, Carvalho J (2011) Multicomponent training program with weight-bearing exercises elicits favorable bone density, muscle strength, and balance adaptations in older women. Calcif Tissue Int 88:117–129. doi:10.1007/s00223-010-9437-1

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Booth FW, Roberts CK, Laye MJ (2012) Lack of exercise is a major cause of chronic diseases. Compr Physiol 2:1143–1211. doi:10.1002/cphy.c110025

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Landi F, Abbatecola AM, Provinciali M, Corsonello A, Bustacchini S, Manigrasso L, Cherubini A, Bernabei R, Lattanzio F (2010) Moving against frailty: does physical activity matter? Biogerontology 11:537–545. doi:10.1007/s10522-010-9296-1

    Article  PubMed  Google Scholar 

  25. 25.

    Landi F, Russo A, Cesari M, Pahor M, Liperoti R, Danese P, Bernabei R, Onder G (2008) Walking one hour or more per day prevented mortality among older persons: results from ilSIRENTE study. Prev Med 47:422–426. doi:10.1016/j.ypmed.2008.06.020

    Article  PubMed  Google Scholar 

  26. 26.

    Grassi C, Landi F, Delogu G (2014) Lifestyles and ageing: targeting key mechanisms to shift the balance from unhealthy to healthy ageing. Stud Health Technol Inform 203:99–111. doi:10.3233/978-1-61499-425-1-99

    PubMed  Google Scholar 

  27. 27.

    Vetrano DL, Martone AM, Mastropaolo S, Tosato M, Colloca G, Marzetti E, Onder G, Bernabei R, Landi F (2013) Prevalence of the seven cardiovascular health metrics in a Mediterranean country: results from a cross-sectional study. Eur J Public Health 23:858–862. doi:10.1093/eurpub/ckt130

    Article  PubMed  Google Scholar 

  28. 28.

    Pahor M, Guralnik JM, Ambrosius WT, Blair S, Bonds DE, Church TS, Espeland MA, Fielding RA, Gill TM, Groessl EJ, King AC, Kritchevsky SB, Manini TM, McDermott MM, Miller ME, Newman AB, Rejeski WJ, Sink KM, Williamson JD (2014) Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial. JAMA 311:2387–2396. doi:10.1001/jama.2014.5616

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Pahor M, Blair SN, Espeland M, Fielding R, Gill TM, Guralnik JM, Hadley EC, King AC, Kritchevsky SB, Maraldi C, Miller ME, Newman AB, Rejeski WJ, Romashkan S, Studenski S (2006) Effects of a physical activity intervention on measures of physical performance: results of the lifestyle interventions and independence for Elders Pilot (LIFE-P) study. J Gerontol A Biol Sci Med Sci 61:1157–1165

    Article  PubMed  Google Scholar 

  30. 30.

    Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB (1994) A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 49:M85–M94. doi:10.1093/geronj/49.2.M85

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Liu CK, Leng X, Hsu FC, Kritchevsky SB, Ding J, Earnest CP, Ferrucci L, Goodpaster BH, Guralnik JM, Lenchik L, Pahor M, Fielding RA (2014) The impact of sarcopenia on a physical activity intervention: the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). J Nutr Health Aging 18:59–64. doi:10.1007/s12603-013-0369-0

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Cesari M, Vellas B, Hsu FC, Newman AB, Doss H, King AC, Manini TM, Church T, Gill TM, Miller ME, Pahor M (2015) A physical activity intervention to treat the frailty syndrome in older persons-results from the LIFE-P study. J Gerontol A Biol Sci Med Sci 70:216–222. doi:10.1093/gerona/glu099

    Article  PubMed  Google Scholar 

  33. 33.

    Marzetti E, Calvani R, Landi F, Hoogendijk EO, Fougere B, Vellas B, Pahor M, Bernabei R, Cesari M (2015) Innovative Medicines Initiative: the SPRINTT Project. J Frailty Aging 4:207–208

    CAS  PubMed Central  Google Scholar 

  34. 34.

    Fielding RA, Rejeski WJ, Blair S, Church T, Espeland MA, Gill TM, Guralnik JM, Hsu FC, Katula J, King AC, Kritchevsky SB, McDermott MM, Miller ME, Nayfield S, Newman AB, Williamson JD, Bonds D, Romashkan S, Hadley E, Pahor M (2011) The lifestyle interventions and independence for elders study: design and methods. J Gerontol A Biol Sci Med Sci 66:1226–1237. doi:10.1093/gerona/glr123

    Article  PubMed  Google Scholar 

  35. 35.

    Cruz-Jentoft AJ, Landi F, Schneider SM, Zuniga C, Arai H, Boirie Y, Chen LK, Fielding RA, Martin FC, Michel JP, Sieber C, Stout JR, Studenski SA, Vellas B, Woo J, Zamboni M, Cederholm T (2014) Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing 43:748–759. doi:10.1093/ageing/afu115

    Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Martone AM, Lattanzio F, Abbatecola AM, Carpia DL, Tosato M, Marzetti E, Calvani R, Onder G, Landi F (2015) Treating sarcopenia in older and oldest old. Curr Pharm Des 21:1715–1722. doi:10.2174/1381612821666150130122032#sthash.xBO96OL5.dpuf

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Calvani R, Miccheli A, Landi F, Bossola M, Cesari M, Leeuwenburgh C, Sieber CC, Bernabei R, Marzetti E (2013) Current nutritional recommendations and novel dietary strategies to manage sarcopenia. J Frailty Aging 2:38–53

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Landi F, Calvani R, Cesari M, Tosato M, Martone AM, Bernabei R, Onder G, Marzetti E (2015) Sarcopenia as the biological substrate of physical frailty. Clin Geriatr Med 31:367–374. doi:10.1016/j.cger.2015.04.005

    Article  PubMed  Google Scholar 

  39. 39.

    Bernabei R, Martone AM, Vetrano DL, Calvani R, Landi F, Marzetti E (2014) Frailty, physical frailty, sarcopenia: a new conceptual model. Stud Health Technol Inform 203:78–84. doi:10.3233/978-1-61499-425-1-78

    PubMed  Google Scholar 

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The present work was funded by a grant from the Innovative Medicines Initiative—Joint Undertaking (IMI-JU 115621). The work was also partly supported by the “Centro Studi Achille e Linda Lorenzon” (E.M., R.C.), Fondazione Roma (NCDs Call for Proposals 2013; E.M., R.C.), and intramural research grants from the Catholic University of the Sacred Heart (D3.2 2013 and D3.2 2015; E.M., F.L., M.T., R.C.).

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Correspondence to Emanuele Marzetti or Francesco Landi.

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Conflict of interest

All of the authors are partners of the SPRINTT consortium, which is partly funded by the European Federation of Pharmaceutical Industries and Associations (EFPIA). E.M. served as a consultant for Huron Consulting Group, Genactis, and Novartis. M.C. served as a consultant for and/or received honoraria for scientific presentations from Nestlé.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Marzetti, E., Calvani, R., Tosato, M. et al. Physical activity and exercise as countermeasures to physical frailty and sarcopenia. Aging Clin Exp Res 29, 35–42 (2017).

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  • Skeletal muscle
  • Physical performance
  • Exercise
  • Resistance training
  • Endurance training