Live strong and prosper: the importance of skeletal muscle strength for healthy ageing

Biogerontology

Volumn 17, Issue 3, 2016, Pages 497-510

  McLeod, Michael ^a   Breen, Leigh ^a   Hamilton, D Lee ^b   Philp, Andrew ^a  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b UNIVERSITY OF STIRLING   (United Kingdom)

Author keywords

Health; Physiology; Protein metabolism; Protein synthesis; Skeletal muscle; Strength

Indexed keywords

AGING; BONE MASS; HUMAN; LIFESPAN; MUSCLE MASS; MUSCLE METABOLISM; MUSCLE STRENGTH; NONHUMAN; OSTEOPENIA; PHYSICAL ACTIVITY; PRIORITY JOURNAL; PROTEIN SYNTHESIS; QUALITY OF LIFE; REVIEW; SARCOPENIA; SKELETAL MUSCLE; AGED; EVIDENCE BASED MEDICINE; EXERCISE; FITNESS; HEALTHY LIFESTYLE; LIFE EXPECTANCY; PHYSIOLOGY; PROCEDURES; RISK REDUCTION; TREATMENT OUTCOME; VERY ELDERLY;

AGED; AGED, 80 AND OVER; AGING; EVIDENCE-BASED MEDICINE; HEALTHY LIFESTYLE; HUMANS; LIFE EXPECTANCY; MUSCLE STRENGTH; MUSCLE, SKELETAL; PHYSICAL CONDITIONING, HUMAN; PHYSICAL FITNESS; QUALITY OF LIFE; RISK REDUCTION BEHAVIOR; TREATMENT OUTCOME;

EID: 84954525088     PISSN: 13895729     EISSN: 15736768     Source Type: Journal    
DOI: 10.1007/s10522-015-9631-7     Document Type: Review

References (156)

1. Abraham RT (1996) Phosphatidylinositol 3-kinase related kinases. Curr Opin Immunol 8:412–418
2. Andersen JL (2003) Muscle fibre type adaptation in the elderly human muscle. Scand J Med Sci Sports 13:40–47
3. Anderson AL et al (2011) Dietary patterns and survival of older adults. J Am Diet Assoc 111:84–91
4. Atherton PJ, Smith K, Etheridge T, Rankin D, Rennie MJ (2010) Distinct anabolic signalling responses to amino acids in C2C12 skeletal muscle cells. Amino Acids 38:1533–1539
5. Avin KG, Law LA (2011) Age-related differences in muscle fatigue vary by contraction type: a meta-analysis. Phys Ther 91:1153–1165. doi:10.2522/ptj.20100333
6. Bauer J et al (2013) Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J Am Med Dir Assoc 14:542–559
7. Baumgartner R (2000) Body composition in healthy aging. Ann N Y Acad Sci 904:437–448
8. Baumgartner RN et al (1998) Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 147:755–763
9. Betik AC, Hepple RT (2008) Determinants of VO2 max decline with aging: an integrated perspective applied physiology, nutrition, and metabolism. Physiol Appl Nutr Metab 33:130–140. doi:10.1139/H07-174
10. Bodine SC et al (2001) Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 3:1014–1019. doi:10.1038/ncb1101-1014
11. Bohé J, Low J, Wolfe RR, Rennie MJ (2001) Rapid report. J Physiol 532:575–579
12. Borst SE (2004) Interventions for sarcopenia and muscle weakness in older people. Age Ageing 33:548–555. doi:10.1093/ageing/afh201
13. Breen L et al (2013) Two weeks of reduced activity decreases leg lean mass and induces “anabolic resistance” of myofibrillar protein synthesis in healthy elderly. J Clin Endocrinol Metab 98:2604–2612
14. Brook MS, Wilkinson DJ, Phillips BE, Perez-Schindler J, Philp A, Smith K, Atherton PJ (2015) Skeletal muscle homeostasis and plasticity in youth and ageing: impact of nutrition and exercise. Acta Physiol. doi:10.1111/apha.12532
15. Brown W (1972) A method for estimating the number of motor units in thenar muscles and the changes in motor unit count with ageing. J Neurol Neurosurg Psychiatry 35:845–852
16. Brunn GJ, Fadden P, Haystead TA, Lawrence JC Jr (1997) The mammalian target of rapamycin phosphorylates sites having a (Ser/Thr)-Pro motif and is activated by antibodies to a region near its COOH terminus. J Biol Chem 272:32547–32550
17. Burd NA et al (2010) Low-load high volume resistance exercise stimulates muscle protein synthesis more than high-load low volume resistance exercise in young men. PloS One 5:e12033
18. Burd NA, Wall BT, van Loon LJ (2012) The curious case of anabolic resistance: old wives’ tales or new fables? J Appl Physiol 112:1233–1235
19. Campbell WW, Trappe TA, Wolfe RR, Evans WJ (2001) The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle The. J Gerontol A Biol Sci Med Sci 56:M373–M380
20. Candow DG, Chilibeck PD, Facci M, Abeysekara S, Zello GA (2006) Protein supplementation before and after resistance training in older men. Eur J Appl Physiol 97:548–556
21. Cassilhas RC, Viana VA, Grassmann V, Santos RT, Santos RF, Tufik S, Mello MT (2007) The impact of resistance exercise on the cognitive function of the elderly. Med Sci Sports Exerc 39:1401
22. Cawood A, Elia M, Stratton R (2012) Systematic review and meta-analysis of the effects of high protein oral nutritional supplements. Ageing Res Rev 11:278–296
23. Cerqueira FM, Kowaltowski AJ (2010) Commonly adopted caloric restriction protocols often involve malnutrition. Ageing Res Rev 9:424–430. doi:10.1016/j.arr.2010.05.002
24. Chesley A, MacDougall J, Tarnopolsky M, Atkinson S, Smith K (1992) Changes in human muscle protein synthesis after resistance exercise. J Appl Physiol 73:1383–1388
25. Clark BC, Fernhall B, Ploutz-Snyder LL (2006) Adaptations in human neuromuscular function following prolonged unweighting: I. Skeletal muscle contractile properties and applied ischemia efficacy. J Appl Physiol 101:256–263
26. Clark BC, Manini TM (2008) Sarcopenia =/= dynapenia. J Gerontol A Biol Sci Med Sci 63:829–834
27. Clark BC, Manini TM (2012) What is dynapenia? Nutrition 28:495–503
28. Covinsky KE, Martin GE, Beyth RJ, Justice AC, Sehgal AR, Landefeld CS (1999) The relationship between clinical assessments of nutritional status and adverse outcomes in older hospitalized medical patients. J Am Geriatr Soc 47:532–538
29. Cruz-Jentoft AJ et al (2010) Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing 39:412–423. doi:10.1093/ageing/afq034
30. Culjkovic B, Topisirovic I, Skrabanek L, Ruiz-Gutierrez M, Borden KL (2005) eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3’UTR. J Cell Biol 169:245–256
31. Cuthbertson D et al (2005) Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J 19:422–424
32. Delmonico MJ et al (2009) Longitudinal study of muscle strength, quality, and adipose tissue infiltration. Am J Clin Nutr 90:1579–1585. doi:10.3945/ajcn.2009.28047
33. Devine A, Dick IM, Islam AF, Dhaliwal SS, Prince RL (2005) Protein consumption is an important predictor of lower limb bone mass in elderly women. Am J Clin Nutr 81:1423–1428
34. Dickinson JM et al (2011) Mammalian target of rapamycin complex 1 activation is required for the stimulation of human skeletal muscle protein synthesis by essential amino acids. J Nutr 141:856–862
35. Drake JC, Peelor FF, Biela LM, Watkins MK, Miller RA, Hamilton KL, Miller BF (2013) Assessment of mitochondrial biogenesis and mTORC1 signaling during chronic rapamycin feeding in male and female mice. J Gerontol A Biol Sci Med Sci 68:1493–1501
36. Drummond MJ et al (2009) Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis. J Physiol 587:1535–1546. doi:10.1113/jphysiol.2008.163816
37. Drummond MJ et al (2012) Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults. Am J Physiol Endocrinol Metab 302:E1113–E1122
38. Einsiedel L, Luff A (1992) Alterations in the contractile properties of motor units within the ageing rat medial gastrocnemius. J Neurol Sci 112:170–177
39. Fenton TR, Eliasziw M, Lyon AW, Tough SC, Hanley DA (2008) Meta-analysis of the quantity of calcium excretion associated with the net acid excretion of the modern diet under the acid-ash diet hypothesis. Am J Clin Nutr 88:1159–1166
40. Fenton TR, Eliasziw M, Tough SC, Lyon AW, Brown JP, Hanley DA (2010) Low urine pH and acid excretion do not predict bone fractures or the loss of bone mineral density: a prospective cohort study. BMC Musculoskelet Disord 11:88. doi:10.1186/1471-2474-11-88
41. Fenton TR, Lyon AW, Eliasziw M, Tough SC, Hanley DA (2009a) Meta-analysis of the effect of the acid-ash hypothesis of osteoporosis on calcium balance. J Bone Mineral Res 24:1835–1840. doi:10.1359/jbmr.090515
42. Fenton TR, Lyon AW, Eliasziw M, Tough SC, Hanley DA (2009b) Phosphate decreases urine calcium and increases calcium balance: a meta-analysis of the osteoporosis acid-ash diet hypothesis. Nutr J 8:41. doi:10.1186/1475-2891-8-41
43. Fiatarone MA et al (1994) Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med 330:1769–1775
44. FIFoA-R (2008) Older Americans 2008: key indicators of well-being. Government Printing Office
45. Fingar DC, Blenis J (2004) Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 23:3151–3171
46. Fingar DC, Salama S, Tsou C, Harlow E, Blenis J (2002) Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev 16:1472–1487
47. Geirsdottir O, Arnarson A, Briem K, Ramel A, Jonsson P, Thorsdottir I (2012a) Effect of 12-week resistance exercise program on body composition, muscle strength, physical function, and glucose metabolism in healthy, insulin-resistant, and diabetic elderly Icelanders. J Gerontol Ser 10:Agls096
48. Geirsdottir OG, Arnarson A, Briem K, Ramel A, Tomasson K, Jonsson P, Thorsdottir I (2012b) Physical function predicts improvement in quality of life in elderly Icelanders after 12 weeks of resistance exercise. J Nutr Health Aging 16:62–66
49. Gelfi C et al (2006) The human muscle proteome in aging. J Proteome Res 5:1344–1353
50. Gingras AC, Raught B, Sonenberg N (2004) mTOR signaling to translation. Curr Top Microbiol Immunol 279:169–197
51. Guertin DA et al (2006) Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell 11:859–871
52. Guevara-Aguirre J et al (2011) Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med 3:70ra13–70ra13
53. Guillet C et al (2004) Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans. FASEB J 18:1586–1587
54. Hakkinen K et al (1998) Changes in muscle morphology, electromyographic activity, and force production characteristics during progressive strength training in young and older men. J Gerontol Ser A, Biol Sci Med Sci 53:B415–B423
55. Hannan KM et al (2003) mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF. Mol Cell Biol 23:8862–8877
56. Hara K et al (2002) Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110:177–189
57. Harber MP, Konopka AR, Douglass MD, Minchev K, Kaminsky LA, Trappe TA, Trappe S (2009) Aerobic exercise training improves whole muscle and single myofiber size and function in older women. Am J Physiol Regul Integr Comp Physiol 297:R1452–1459. doi:10.1152/ajpregu.00354.2009
58. Harrison DE et al (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–395
59. Haskell W et al (2007) Physical Activity and Public Health: Updated Recommendation for Adults from the American College of Sports Medicine and the American Heart Association Medicine and Science in sports and exercise. Circulation 39:1423–1434
60. Holloszy JO, Coyle EF (1984) Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol 56:831–838
61. Holloszy JO, Larsson L (1995) Motor units: remodeling in aged animals The. J Gerontol A Biol Sci Med Sci 50:91–95
62. Janssen I, Heymsfield SB, Ross R (2002) Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J Am Geriatr Soc 50:889–896
63. Janssen I, Heymsfield SB, Wang ZM, Ross R (2000) Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr. J Appl Physiol 89:81–88
64. Jia K, Chen D, Riddle DL (2004) The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development (Cambridge, England) 131:3897–3906. doi:10.1242/dev.01255
65. Josse AR, Atkinson SA, Tarnopolsky MA, Phillips SM (2011) Increased consumption of dairy foods and protein during diet- and exercise-induced weight loss promotes fat mass loss and lean mass gain in overweight and obese premenopausal women. J Nutr 141:1626–1634. doi:10.3945/jn.111.141028
66. Kadi F, Charifi N, Denis C, Lexell J (2004) Satellite cells and myonuclei in young and elderly women and men Muscle & nerve 29:120–127
67. Kaeberlein M et al (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science (New York, NY) 310:1193–1196
68. Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW-L, Thomas EL, Kockel L (2010) With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab 11:453–465
69. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S (2004) Regulation of Lifespan in < i > Drosophila by Modulation of Genes in the TOR Signaling Pathway. Curr Biol 14:885–890
70. Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR (2005) Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids. Am J Clin Nutr 82:1065–1073
71. Kent-Braun JA, Ng AV, Young K (2000) Skeletal muscle contractile and noncontractile components in young and older women and men. J Appl Physiol 88:662–668
72. Kim DH et al (2003) GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell 11:895–904
73. Kim I-Y et al (2015) Quantity of dietary protein intake, but not pattern of intake, affects net protein balance primarily through differences in protein synthesis in older adults. Am J Physiol Endocrinol Metab 308:E21–E28
74. Kortebein P et al (2008) Functional impact of 10 days of bed rest in healthy older adults. J Gerontol Ser A, Biol Sci Med Sci 63:1076–1081
75. Kosek DJ, Kim JS, Petrella JK, Cross JM, Bamman MM (2006) Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults. J Appl Physiol (Bethesda, Md: 1985) 101:531–544
76. Kubica N, Bolster DR, Farrell PA, Kimball SR, Jefferson LS (2005) Resistance exercise increases muscle protein synthesis and translation of eukaryotic initiation factor 2Bepsilon mRNA in a mammalian target of rapamycin-dependent manner. J Biol Chem 280:7570–7580
77. Kuk JL, Saunders TJ, Davidson LE, Ross R (2009) Age-related changes in total and regional fat distribution. Ageing Res Rev 8:339–348. doi:10.1016/j.arr.2009.06.001
78. Kumar V et al (2009) Age-related differences in the dose–response relationship of muscle protein synthesis to resistance exercise in young and old men. J Physiol 587:211–217
79. Lambert CP, Evans WJ (2005) Adaptations to aerobic and resistance exercise in the elderly. Rev Endocr Metab Disord 6:137–143. doi:10.1007/s11154-005-6726-5
80. Landi F et al (2012a) Sarcopenia and mortality among older nursing home residents. J Am Med Dir Assoc 13:121–126. doi:10.1016/j.jamda.2011.07.004
81. Landi F et al (2012b) Sarcopenia as a risk factor for falls in elderly individuals: results from the ilSIRENTE study. Clin Nutr 31:652–658. doi:10.1016/j.clnu.2012.02.007
82. Lang T, Streeper T, Cawthon P, Baldwin K, Taaffe DR, Harris TB (2010) Sarcopenia: etiology, clinical consequences, intervention, and assessment. Osteoporos Int 21:543–559
83. Lee CD, Blair SN, Jackson AS (1999) Cardiorespiratory fitness, body composition, and all-cause and cardiovascular disease mortality in men. Am J Clin Nutr 69:373–380
84. Lee CH, Inoki K, Guan KL (2007) mTOR pathway as a target in tissue hypertrophy. Annu Rev Pharmacol Toxicol 47:443–467
85. Lee DC, Artero EG, Sui X, Blair SN (2010) Mortality trends in the general population: the importance of cardiorespiratory fitness. J Psychopharmacol 24:27–35. doi:10.1177/1359786810382057
86. Lee DC et al (2011) Comparisons of leisure-time physical activity and cardiorespiratory fitness as predictors of all-cause mortality in men and women. Br J Sports Med 45:504–510. doi:10.1136/bjsm.2009.066209
87. Leenders M, Verdijk LB, van der Hoeven L, van Kranenburg J, Nilwik R, van Loon LJ (2013) Elderly men and women benefit equally from prolonged resistance-type exercise training The. J Gerontol A Biol Sci Med Sci 68:769–779
88. Levinger I, Goodman C, Hare DL, Jerums G, Selig S (2009) Functional capacity and quality of life in middle-age men and women with high and low number of metabolic risk factors. Int J Cardiol 133:281–283
89. Lexell J (1995) Human aging, muscle mass, and fiber type composition. J Gerontol Ser A, Biol Sci Med Sci 50(Spec No):11–16
90. Luff AR (1998) Age-associated changes in the innervation of muscle fibers and changes in the mechanical properties of motor units. Ann N Y Acad Sci 854:92–101
91. Ma XM, Yoon SO, Richardson CJ, Julich K, Blenis J (2008) SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs. Cell 133:303–313. doi:10.1016/j.cell.2008.02.031
92. Macaluso A, De Vito G (2004) Muscle strength, power and adaptations to resistance training in older people. Eur J Appl Physiol 91:450–472
93. Manini TM et al (2007) Knee extension strength cutpoints for maintaining mobility. J Am Geriatr Soc 55:451–457
94. Martin B, Ji S, Maudsley S, Mattson MP (2010) “Control” laboratory rodents are metabolically morbid: why it matters. Proc Natl Acad Sci 107:6127–6133
95. McCartney N, Hicks AL, Martin J, Webber CE (1995) Long-term resistance training in the elderly: effects on dynamic strength, exercise capacity, muscle, and bone. J Gerontol Ser A, Biol Sci Med Sci 50:B97–B104
96. Meng X, Zhu K, Devine A, Kerr DA, Binns CW, Prince RL (2009) A 5-year cohort study of the effects of high protein intake on lean mass and BMC in elderly postmenopausal women. J Bone Miner Res 24:1827–1834
97. Mettler S, Mitchell N, Tipton KD (2010) Increased protein intake reduces lean body mass loss during weight loss in athletes. Med Sci Sports Exerc 42:326–337. doi:10.1249/MSS.0b013e3181b2ef8e
98. Mitchell WK, Phillips BE, Williams JP, Rankin D, Lund JN, Smith K, Atherton PJ (2015) A Dose-rather than Delivery Profile-Dependent Mechanism Regulates the “Muscle-Full” Effect in Response to Oral Essential Amino Acid Intake in Young Men. J Nutr 145:207–214
99. Mitchell WK, Phillips BE, Williams JP, Rankin D, Smith K, Lund JN, Atherton PJ (2013) Development of a new Sonovue™ contrast-enhanced ultrasound approach reveals temporal and age-related features of muscle microvascular responses to feeding. Physiol Rep 1:e00119
100. Mitchell WK, Williams J, Atherton P, Larvin M, Lund J, Narici M (2012) Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative. Rev Front Physiol 3:260
101. Montero-Fernandez N, Serra-Rexach JA (2013) Role of exercise on sarcopenia in the elderly. Eur J Phys Rehabil Med 49:131–143
102. Moore DR, Churchward-Venne TA, Witard O, Breen L, Burd NA, Tipton KD, Phillips SM (2015) Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men. J Gerontol Ser A, Biol Sci Med Sci 70:57–62. doi:10.1093/gerona/glu103
103. Morley JE et al (2010) Nutritional recommendations for the management of sarcopenia. J Am Med Dir Assoc 11:391–396
104. Murton AJ, Marimuthu K, Mallinson JE, Selby AL, Smith K, Rennie MJ, Greenhaff PL (2015) Obesity appears to be associated with altered muscle protein synthetic and breakdown responses to increased nutrient delivery in older men, but not reduced muscle mass or contractile function. Diabetes 26: db150021
105. Narici MV et al (1996) Human quadriceps cross-sectional area, torque and neural activation during 6 months strength training. Acta Physiol Scand 157:175–186
106. Narici MV, Maganaris CN, Reeves ND, Capodaglio P (2003) Effect of aging on human muscle architecture. J Appl Physiol (Bethesda, Md: 1985) 95: 2229–2234 doi: 10.1152/japplphysiol.00433.2003
107. Newman AB et al (2006) Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J Gerontol A Biol Sci Med Sci 61:72–77
108. Nilsson MI et al (2013) Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity. FASEB J 27:3905–3916
109. Onder G, Della Vedova C, Landi F (2009) Validated treatments and therapeutics prospectives regarding pharmacological products for sarcopenia. JNHA: J Nutr Health Aging 13:746–756
110. Orr R, Raymond J, Singh MF (2008) Efficacy of progressive resistance training on balance performance in older adults. Sports Med 38:317–343
111. Paddon-Jones D et al (2004) Amino acid ingestion improves muscle protein synthesis in the young and elderly. Am J Physiol-Endocrinol Metab 286:E321–E328
112. Panel on Prevention of Falls in Older Persons AGS, British Geriatrics S (2011) Summary of the Updated American Geriatrics Society/British Geriatrics Society clinical practice guideline for prevention of falls in older persons. J Am Geriatr Soc 59:148–157. doi:10.1111/j.1532-5415.2010.03234.x
113. Pearce LR et al (2007) Identification of Protor as a novel Rictor-binding component of mTOR complex-2. Biochem J 405:513–522
114. Pennings B, Koopman R, Beelen M, Senden JM, Saris WH, van Loon LJ (2011) Exercising before protein intake allows for greater use of dietary protein–derived amino acids for de novo muscle protein synthesis in both young and elderly men. Am J Clin Nutr 93:322–331
115. Phillips SM (2014) A brief review of higher dietary protein diets in weight loss: a focus on athletes. Sports Med 44(Suppl 2):S149–S153. doi:10.1007/s40279-014-0254-y
116. Pichard C, Kyle UG, Morabia A, Perrier A, Vermeulen B, Unger P (2004) Nutritional assessment: lean body mass depletion at hospital admission is associated with an increased length of stay. Am J Clin Nutr 79:613–618
117. Rosenberg IH (1989) Summary comments. Am J Clin Nutr 50:1231–1233
118. Rubenstein LZ, Josephson KR, Trueblood PR, Loy S, Harker JO, Pietruszka FM, Robbins AS (2000) Effects of a group exercise program on strength, mobility, and falls among fall-prone elderly men. J Gerontol Ser A, Biol Sci Med Sci 55:M317–M321
119. Ruiz JR et al (2009) Muscular strength and adiposity as predictors of adulthood cancer mortality in men Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive. Oncology 18:1468–1476. doi:10.1158/1055-9965.EPI-08-1075
120. Ruiz JR, Sui X, Lobelo F, Morrow JR Jr, Jackson AW, Sjostrom M, Blair SN (2008) Association between muscular strength and mortality in men: prospective cohort study. Bmj 337:a439. doi:10.1136/bmj.a439
121. Sarbassov DD et al (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14:1296–1302
122. Schalm SS, Blenis J (2002) Identification of a conserved motif required for mTOR signaling. Curr Biol 12:632–639
123. Schalm SS, Fingar DC, Sabatini DM, Blenis J (2003) TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Curr Biol 13:797–806
124. Schrager MA, Metter EJ, Simonsick E, Ble A, Bandinelli S, Lauretani F, Ferrucci L (2007) Sarcopenic obesity and inflammation in the InCHIANTI study. J Appl Physiol 102:919–925
125. Schurch M-A, Rizzoli R, Slosman D, Vadas L, Vergnaud P, Bonjour J-P (1998) Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 128:801–809
126. Selman C et al (2009) Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326:140–144
127. Sharp ZD, Richardson A (2011) Aging and cancer: can mTOR inhibitors kill two birds with one drug? Targ Oncol 6:41–51
128. Sharples AP, Hughes DC, Deane CS, Saini A, Selman C, Stewart CE (2015) Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake. Aging cell 14: 511–523
129. Shevah O, Laron Z (2007) Patients with congenital deficiency of IGF-I seem protected from the development of malignancies: a preliminary report. Growth Hormon IGF Res 17:54–57
130. Short KR, Nair KS (2000) The effect of age on protein metabolism. Curr Opin Clin Nutr Metab Care 3:39–44
131. Sitnick M, Bodine SC, Rutledge JC (2009) Chronic high fat feeding attenuates load-induced hypertrophy in mice. J Physiol 587:5753–5765
132. Stenholm S, Harris TB, Rantanen T, Visser M, Kritchevsky SB, Ferrucci L (2008) Sarcopenic obesity: definition, cause and consequences. Curr Opin Clin Nutr Metab Care 11:693–700. doi:10.1097/MCO.0b013e328312c37d
133. Stephens FB, Chee C, Wall BT, Murton AJ, Shannon CE, van Loon LJ, Tsintzas K (2015) Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men. Diabetes 64:1615–1620
134. Studenski S et al (2011) Gait speed and survival in older adults. Jama 305:50–58
135. Takata Y et al (2012) Physical fitness and 6.5-year mortality in an 85-year-old community-dwelling population. Arch Gerontol Geriatr 54:28–33
136. Taylor BJ, Johnson BD (2010) The pulmonary circulation and exercise responses in the elderly. In: Seminars in respiratory and critical care medicine, vol 5. NIH Public Access, p 528
137. Tieland M, Borgonjen-Van den Berg KJ, van Loon LJ, de Groot LC (2012) Dietary protein intake in community-dwelling, frail, and institutionalized elderly people: scope for improvement. Eur J Nutr 51:173–179
138. Tipton KD, Ferrando AA, Phillips SM, Doyle D, Wolfe RR (1999) Postexercise net protein synthesis in human muscle from orally administered amino acids. Am J Physiol Endocrinol Metab 276:E628–E634
139. Tomlinson B, Irving D (1977) The numbers of limb motor neurons in the human lumbosacral cord throughout life. J Neurol Sci 34:213–219
140. Topinkova E (2008) Aging, disability and frailty Annals of nutrition & metabolism 52 Suppl 1:6-11 doi: 10.1159/000115340
141. Topisirovic I, Culjkovic B, Cohen N, Perez JM, Skrabanek L, Borden KL (2003) The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth. EMBO J 22:689–703
142. Topisirovic I, Ruiz-Gutierrez M, Borden KL (2004) Phosphorylation of the eukaryotic translation initiation factor eIF4E contributes to its transformation and mRNA transport activities. Cancer Res 64:8639–8642
143. Trappe T, Burd N, Louis E, Lee G, Trappe S (2007) Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women. Acta Physiol 191:147–159
144. Visser M et al (2005) Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons The. J Gerontol A Biol Sci Med Sci 60:324–333
145. Vitale G et al (2012) Low circulating IGF-I bioactivity is associated with human longevity: findings in centenarians’ offspring. Aging (Albany NY) 4:580
146. Volpi E, Mittendorfer B, Rasmussen BB, Wolfe RR (2000) The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly 1. J Clin Endocrinol Metab 85:4481–4490
147. Volpi E, Mittendorfer B, Wolf SE, Wolfe RR (1999) Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction. Am J Physiol-Endocrinol Metab 277:E513–E520
148. Walker DK et al (2011) Exercise, amino acids, and aging in the control of human muscle protein synthesis. Med Sci Sports Exerc 43:2249–2258. doi:10.1249/MSS.0b013e318223b037
149. Wellen KE, Hotamisligil GS (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Investig 112:1785
150. Wilkinson D et al (2013) Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism. J Physiol 591:2911–2923
151. Wilkinson DJ et al (2014) A validation of the application of D(2)O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans. Am J Physiol Endocrinol Metab 306: E571–579 doi: 10.1152/ajpendo.00650.2013
152. Williams MA et al (2007) Resistance exercise in individuals with and without cardiovascular disease: 2007 update a scientific statement from the american heart association council on clinical cardiology and council on nutrition, physical activity, and metabolism. Circulation 116:572–584
153. Wolfe RR (2006) The underappreciated role of muscle in health and disease. Am J Clin Nutr 84:475–482
154. Woo SY et al (2007) PRR5, a novel component of mTOR complex 2, regulates platelet-derived growth factor receptor beta expression and signaling. J Biol Chem 282:25604–25612
155. Yang Q, Inoki K, Ikenoue T, Guan KL (2006) Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes Dev 20:2820–2832
156. Zoncu R, Efeyan A, Sabatini DM (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12:21–35