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Aging and disease    2019, Vol. 10 Issue (1) : 157-173     DOI: 10.14336/AD.2018.0325
Review |
Prospective Views for Whey Protein and/or Resistance Training Against Age-related Sarcopenia
Yuxiao Liao1,2, Zhao Peng1,2, Liangkai Chen1,2, Yan Zhang1,2, Qian Cheng1,2, Andreas K. Nüssler3, Wei Bao4, Liegang Liu1,2, Wei Yang1,2,*
1Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
2MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
3Department of Traumatology, BG Trauma center, University of Tübingen, Tübingen, Germany.
4Department of Epidemiology, College of Public Health, University of Iowa, IA 52242, USA.
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Skeletal muscle aging is characterized by decline in skeletal muscle mass and function along with growing age, which consequently leads to age-related sarcopenia, if without any preventive timely treatment. Moreover, age-related sarcopenia in elder people would contribute to falls and fractures, disability, poor quality of life, increased use of hospital services and even mortality. Whey protein (WP) and/or resistance training (RT) has shown promise in preventing and treating age-related sarcopenia. It seems that sex hormones could be potential contributors for gender differences in skeletal muscle and age-related sarcopenia. In addition, skeletal muscle and the development of sarcopenia are influenced by gut microbiota, which in turn is affected by WP or RT. Gut microbiota may be a key factor for WP and/or RT against age-related sarcopenia. Therefore, focusing on sex hormones and gut microbiota may do great help for preventing, treating and better understanding age-related sarcopenia.

Keywords age-related sarcopenia      whey protein      resistance training      sex hormones      gender differences      gut microbiota     
Corresponding Authors: Yang Wei   
About author:

These authors contributed equally.

Issue Date: 06 January 2018
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Liao Yuxiao
Peng Zhao
Chen Liangkai
Zhang Yan
Cheng Qian
Nüssler Andreas K.
Bao Wei
Liu Liegang
Yang Wei
Cite this article:   
Liao Yuxiao,Peng Zhao,Chen Liangkai, et al. Prospective Views for Whey Protein and/or Resistance Training Against Age-related Sarcopenia[J]. Aging and disease, 2019, 10(1): 157-173.
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Figure 1.  Gut microbiota and muscle aging. Age-related lifestyles, including decreased physical function, nutrition intake and living status, would induced the changes of gut microbiota. The increased Bifidobacteria, Christensenellaceae, and Akkermansia were identified as aging-core-microbiota. The substantial microbiome change in aging may affect changes in gut physiology such as reduced gut motility, reduced mucus, barrier dysfunction, and dysbiosis, which can further mediate the translocation of bacterial toxins and muscle aging. “+” means increased, “-” means decreased.
Figure 2.  Mechanism of whey protein/resistance training to induce muscle protein synthesis. Amino acids (AAs)/resistance training, together with insulin, promote the muscle protein synthesis (MPS) by affecting the components of the phosphatidylinositol 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling pathway, as described in detail in the text. “?”: whether or not AAs directly promote activation of mTOR remains unknown; ?: phosphorylate; PKB: protein kinase B; GSK3: glycogen synthase kinase 3; 4E-BP1: eIF4E-binding protein 1; p70S6k: 70 kDa ribosomal protein S6 protein kinase; elF2B/4E/4G: eukaryotic initiation factor 2B/4E/4G.
Figure 3.  Schematic diagram of paper structure. Whey protein/resistance training indeed contributed to age-related sarcopenia in elder people. Besides, it seems that sex hormones could be a potential contributor to muscle health based on the discussion of gender differences in skeletal muscle and sarcopenia. Furthermore, we proposed that gut microbiota may be a key factor in the combination of whey protein and resistance training against age-related sarcopenia.
Human (WP combined with RT)
Burd et al.
14 healthy elderly men (72 y)20g WP isolate or 20g micellar CA immediately after unilateral leg RTgreater MPS in WP isolate than micellar CA both at rest and after RT
Mitchell et al. [26]
D’Souza et al. [119]
13 healthy older men (60-75 y)
46 healthy older men (69.0 ± 0.6 y)
30g WP, 30g SP or a noncaloric placebo immediately after a single bout of unaccustomed lower body RTphosphorylation of S6K1↑ in SP only at 2h post exercise but in WP at 2h and 4h post exercise
Luiking et al. [29]20 healthy older persons (> 60 y)20g leucine-enriched WP (3g leucine) or 6g iso-caloric milk protein immediately after unilateral RTgreater postprandial MPS rate in leucine-enriched WP than milk protein after unilateral RT.
West et al.
12 young trained men (24.0 ± 4.0 y)25g WP or iso-caloric placebo at 0h and 10h after an acute bout of RTwhole body net protein balance↑ in WP after RT over 10h and 24h compared to the placebo
Tang et al.
18 healthy young men (22.8 ± 3.9 y)21.4g WP, 21.9g CA, or 22.2g SP at rest and immediately after a bout of unilateral leg RTgreater MPS in WP or SP than CA both at rest and after RT; greater MPS in WP than SP after RT
Bell et al.
49 healthy older men (73.0 ± 1.0 y)WP-based supplement or a control drink twice daily for 20 weeks (Phase 1); twice weekly RT and once weekly HIIT for 12 weeks after 6 weeks of Phase 1.MS↑ and lean mass↑ in WP-based supplement; greater MS after RT
Bukhari et al. [71]16 postmenopausal women (66.0 ± 3.0 y)20g WP or 3g leucine-enriched EAA immediately after a bout of unilateral RTEquivalent muscle anabolism in WP and leucine-rich EAA at rest and after exercise
Weisgarber et al. [72]12 postmenopausal
women (57.0 ± 4.7 y)
WP ((4 × 10g aliquots)) or placebo (maltodextrin) during unilateral RT twice weekly for 10 weeks.muscle mass↑ and strength↑ after high volume RT; WP during RT did not augment this response
Karelis et al. [81]99 healthy elderly subjects (65-88 y)20 g/day cysteine-rich WP isolate or CA for 135 days, with RT 3 times weeklygreater MS in WP isolate than CA after RT
Farnfield et al. [112]16 healthy young (18-25 y) and 15 healthy older men (60-75 y)WP isolate or placebo drink after each session of RT for 12 weeksprotein phosphorylation↑ in WP isolate with RT; WP- and RT-induced protein phosphorylation↓ in older men, but not in younger men
D’Souza et al. [119]46 healthy older men (69.0 ± 0.6 y)10, 20, 30, or 40g of WP or a noncaloric placebo beverage immediately after a single bout of unaccustomed lower body RTmuscle BCAAs↑ during post exercise recovery and larger doses (30 g and 40 g) of WP
Rondanelli et al. [85]130 sarcopenic elderly people (80.3 y)A supplement containing 22g WP, 10.9g EAA (4 g leucine), and vitamin D [2.5 mg (100 IU)] with RT for 12 weeksFFM↑, relative skeletal muscle mass↑, android distribution of fat↑, and handgrip strength↑ after supplement plus RT
Verreijen et al. [87]80 obese older adults (63.0 ± 5.6 y)high whey protein-, leucine-, and vitamin D-enriched supplement (21 g protein; 10×/week) or an isocaloric control with RT 3×/week for 13 weeksgreater appendicular muscle mass in the intervention than control groups
Engelen et al. [88]8 COPD patients (68.1 ± 2.2 y) and
8 healthy subjects (63.1 ± 2.8 y)
29.5g WP or sodium caseinate with a cycle test for 2 dayshigher prandial and whole body protein anabolism in CA than WP in COPD patients
Björkman et al. [89]47 older polymyalgia
rheumatica patients (69.5 y)
The experimental group (whey: CA = 80:20) or control group (whey: CA = 20:80) twice daily after RT for 8 weekslower limb muscle mass↑, walking speed↑ and chair stand test performance↑ after the post-exercise supplementation
Bemben et al. [101]42 male subjects
(48-72 y)
3 days per week for 14 weeks of RT supplemented with 5g creatine and/or 35g WPMS↑ and lean body mass↑ after RT with no additional benefits from supplement
Yang et al. [108]37 elderly men
(71.0 ± 4.0 y)
0, 10, 20 or 40g WP isolate after a bout of unilateral leg-based RT.Greatest MPS in 20g WP at rest; MPS↑ at all protein doses after RT, but greatest MPS in 40g WP.
DeNysschen et al. [109]28 overweight male subjects (38 y)3-day-a-week cycle for 12 weeks with 25.8g/day soy versus 26.6g/day WP supplementationFFM↑, body fat (%)↓, waist/hip↓ and total serum cholesterol↓ in all groups without differences
Reitelseder et al. [125]17 healthy male subjects (27.0 ± 2.0 y)whey, CA (0.3g/kg lean body mass), or a noncaloric control drink immediately after heavy RTMPS↑ at 1-6 h in whey and CA after exercise; phosphorylation of Akt and S6K1↑ after exercise and protein intake; higher 4E-BP1 after whey than CA
Dideriksen et al. [126]24 elderly persons
(68.0 ± 1.0 years)
caseinate intake 30 mins before heavy RT; whey, caseinate or a non-caloric control drink after heavy RTFSR and MPS does not differ with whey and caseinate after RT, and MPS is similar with caseinate before and after RT.
Human (WP only)
Katsanos et al. [25]15 elderly persons
(60-85 y)
15g WP, 6.72g EAA, or 7.57g of nonessential amino acidsgreater MPS in WP ingestion than ingestion of its constituent EAA content.
Zhu et al.
196 postmenopausal women (74.3 ± 2.7 y)30g WP or 2.1g protein (placebo) daily for 2 yearsno influence on muscle mass or physical function
Kramer et al. [78]45 healthy older men (69.0 ± 1.0 y)21g leucine-enriched WP with and without 9g CHO and 3g fat, or an isocaloric mixture containing CHO and fat onlyMPS rates↑ after WP intake rather than CHO and fat
Bauer et al. [84]380 sarcopenic older adults (≥ 65 years)800 IU vitamin D and 20g leucine-enriched WP (3g leucine) supplement or an iso-caloric control product twice daily for 13 weeksmuscle mass↑ and lower-extremity function↑ after vitamin D and leucine-enriched WP supplement
Hector et al. [86]40 healthy adults
(35-65 y)
27g whey, 26g soy, or 25g CHO twice daily for 12 daysgreater MPS in whey than soy or CHO; postprandial MPS↓ less in whey than in soy and CHO
Paddon-Jones et al. [128]15 healthy elderly individuals (65-79 y)15g EAAs or WP isolatenet phenylalanine uptake↑ and FSR↑ in both groups, but greatest increase in EAA group
Human (RT only)
Reeves et al. [100]18 elder persons
(70.7 y)
Leg-extension and leg-press exercises (2 sets of 10 repetitions at 80% of the 5 repetitions maximum) were performed three times weekly for 14 weeksvastus lateralis muscle fascicle force↑ and muscle volume↑ after exercise
Devries et al. [102]30 healthy older men (70.0 ± 1.0 y)14 days step-reduction (SR) (< 1500 steps/day) with 5g citrulline or glycine daily combined with a unilateral low-load RT thrice weeklyFSR↓ in the SR leg; FFM↑ and FSR↑ in the SR + RT leg; no effect of citrulline on muscle
Van Roie et al. [103]56 older adults
(68.0 ± 5.0 y)
3 times weekly for 12 weeks of high- and low-load RT (the bilateral leg press, leg extension and seated row)no effects of high- and low-load RT on muscle volume, MS and functional capacity
Animals (WP combined with RT)
Mosoni et al. [27]healthy male Wistar ratsCA (12%), WP (12%) or WP (18%) with/without polyphenols/antioxidants for 6 monthsslower loss of lean body mass in WP (~18%); protein type and polyphenol/antioxidant supplementation had no effects
Butteiger et al. [74]healthy male Sprague-Dawley rats20% WP, 20% SP isolate, and two blends (Blend 1 and Blend 2) consisting of ratios of 50:25:25 and 25:50:25 for whey: caseinate: soy, respectivelyMPS↑ in all groups; higher FSR peak in Blend 2 than WP at 135 minutes
Kanda et al. [75]male Sprague-Dawley ratsWP, caseinate, milk protein, or SP (2.4 mL/100 g bw, 3.1g protein/kg bw) immediately after swimming for 2 hoursthe fastest initial peak time in MPS after ingestion of WP at different times
Anthony et al. [110]treadmill-acclimated ratsCHO only, CHO plus SP (CS), or CHO plus WP (CW) immediately after RTgreater phosphorylation of S6K1 and mTOR in CW than in CS
Kanda et al. [127]male Sprague-Dawley ratsiso-caloric (1100 kJ/100 ml) CHO, CHO plus an amino acid mixture or CHO plus WP hydrolysates immediately after exercisegreater phosphorylation of mTOR, 4E-BP1and S6K1, and FSR in WP compared with amino acid
Animals (RT only)
Pasini et al. [105]aged (14-16-month-old) male Wistar ratsa treadmill for 3 or 5 days/week for 8 weeks and compared with age-matched sedentary controlsmuscle weight↑, sarcomere volume↑ after 5 days/week treadmill without affecting body weight; substantial impairments in muscle anabolic pathways↓ after exercise
Table 1  Whey protein and/or resistance training promote muscle health.
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