© 2013 John Wiley & Sons A/S.

Scand J Med Sci Sports 2014: 24: e1–e10 doi: 10.1111/sms.12123

Published by John Wiley & Sons Ltd

Review

Responsiveness of muscle size and strength to physical training in very elderly people: A systematic review V. H. Stewart1, D. H. Saunders2, C. A. Greig1 1

Department of Clinical and Surgical Sciences (Surgery), School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh, UK, 2Institute for Sport, PE & Health Science, University of Edinburgh, Edinburgh, UK Corresponding author: Carolyn Greig, PhD, Department of Clinical and Surgical Sciences (Geriatric Medicine), University of Edinburgh, Room S1642, Royal Infirmary Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK. Tel: +44 131 242 6940/6481, Fax: +44 131 242 6370, E-mail: [email protected] Accepted for publication 13 August 2013

The purpose of this review was to determine whether very elderly muscle (>75 years) hypertrophies in response to physical training. The databases MEDLINE; EMBASE; CINAHL Plus and SPORTDiscus were systematically literature searched with reference lists of all included studies and relevant reviews. Controlled trials (inactive elderly control group) involving healthy elderly participants over 75 years participating in an intervention complying with an established definition of physical training were included. Data extraction and quality assessment were performed using the PEDro scale. Data analysis was performed on muscle size and strength using RevMan (software version 5.1). Four studies were included of

which four of four measured changes in gross muscle size. Training induced increases in muscle size from 1.5%– 15.6% were reported in three of four studies, and one of four studies reported a decrease in muscle size (3%). The greatest gain in muscle mass was observed in a study of whole body vibration training. Meta-analysis of three studies found an increase of thigh muscle cross-sectional area (mean difference 2.31 cm2 or 0.2%, 95% confidence interval (CI): 0.62 to 4.00; P = 0.008) and muscle strength (standardized mean difference 1.04, 95% CI: 0.65 to 1.43; P < 0.001). Physical training when delivered as resistance training has the ability to elicit hypertrophy and increase muscle strength in very elderly muscle.

Sarcopenia is the loss of muscle mass and strength that occurs with advancing age (Cruz-Jentoft et al., 2010; Rosenberg, 2011). Furthermore, these age-related losses contribute significantly to the deterioration of functional ability and subsequent reduction of physical independence that is frequently seen in elderly individuals. Previous research within elderly populations has demonstrated associations between sarcopenia and functional impairment and disability, as well as a high incidence of accidental falls and other medical conditions including arthritis and insulin resistance (Wickham et al., 1989; Janssen et al., 2002; Deschenes, 2004). Progressive resistance training (PRT) is currently the most effective method of increasing muscle size and strength in adult muscle. For example, a recent study demonstrated that an increase in young (20 ± 2 year) muscle quadriceps size at a rate of 0.2% per day could be achieved over the first 20 days of a 5-week program of PRT (Seynnes et al., 2007). Older adults (median age 81) can also increase their muscle strength and power in response to physical training, with the potential to restore strength levels to the highest they had been for an average of 8–12 years prior (Skelton & McLaughlin, 1996). However, it is unclear whether physical training can increase muscle size (vitally important for storage, homeostatic and

metabolic activities; Daniel et al., 1977) and strength in people aged over 75 years, i.e., those in which functional decline accelerates (Svanborg, 1988). This ambiguity is due to the lack of relevant intervention studies in this very elderly age group in particular those reporting controlled comparisons. In addition, there are currently no systematic reviews or meta-analyses of these effects. The aim of this systematic review, conforming to the PRISMA statement (Moher et al., 2009) was to determine whether physical training interventions can increase (a) muscle size and (b) muscle strength in very elderly people (> 75 years) when compared with a nonexercising control group. Materials and methods Search methods for identification of articles The following electronic bibliographic databases were searched on February 6, 2012: MEDLINE (1946 to February 2012) in Ovid (Appendix); EMBASE Classic + EMBASE (1947 to February 2012) in Ovid; CINAHL Plus (1937 to February 2012) in EBSCO; SPORTDiscus (1949 to February 2012) in EBSCO. The MEDLINE search strategy (Appendix) was developed which comprised both controlled vocabulary and free text terms designed to identify (a) the target participants (age > 75 years), (b) the specific intervention (physical training) and (c) the desired outcomes (muscle mass, size,

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Stewart et al. strength, power, muscle fiber size, area). These three domains, each incorporating any synonyms, were combined using the following Boolean logic; “elderly” AND “training” AND (“muscle size OR muscle strength). The MEDLINE search strategy (Appendix) was modified in order to accommodate the searches in the other databases.

analysis was performed using RevMan (2011, software version 5.1).

Results Figure 1 summarizes the process of inclusion of the articles for review and analysis.

Inclusion and exclusion criteria The titles of all citations identified by the electronic searches were screened by one investigator (VS) and any obviously irrelevant reports discarded. Abstracts of potentially eligible articles were retrieved, screened and discarded if the abstract indicated the article did not meet the criteria. Full versions of the remaining results were retrieved and assessed (by VS and CAG or DS) to determine whether the prespecified inclusion criteria were satisfied. Requirements for eligible studies were (a) a randomized or non-randomized controlled trial design comparing a PRT group with a no-exercise control group; (b) inclusion of adults aged 75 years or older or mean age of the intervention/control participant group aged 75 years or older and considered healthy; (c) inclusion of an intervention complying with the definition of training, i.e., “planned, structured, and repetitive and purposive in the sense that the improvement or maintenance of one or more components of physical fitness is the objective” (USDHHS, 2008) and (d) measures of muscle strength and/or measures of muscle and muscle fiber size or cross sectional area. Exclusion criteria were (a) inclusion of adults aged younger than 75 years or an intervention/ control participant group younger than 75 years; (b) noncompliance of the intervention with the definition of training; (c) animal studies. No studies were excluded based on publication status or language.

Data extraction Data were extracted from eligible articles using a standardized form. Data extracted from the papers included participant number and characteristics; descriptions of the intervention and control; statistical analysis techniques; measurement tool or method, unit of measurement and length of follow-up and number of followup measurements for each relevant outcome; the absolute and percentage change of each prespecified outcome. Authors were contacted where necessary for additional information or any clarification.

Quality assessment All articles meeting inclusion criteria were independently rated for quality using the PEDro scale (PEDro, 1999). A score of ≥6/10 on the PEDro scale is indicative of a trial that is of moderate to high quality.

Data synthesis Fixed effect meta-analyses were used to compare included outcomes in training and control groups. Data were included in metaanalyses only if the trial reported a randomized design. For continuous data the pooled mean differences (MD) with 95% confidence interval (CI) were reported. If different scales were employed by the different trials for the assessment of the same outcome (i.e. muscle strength), the standardized mean differences (SMD) with 95% CI were reported. A fixed-effect model was used to pool treatment effects when trials used similar outcome measures on similar populations. When meta-analyses were included, tests of homogeneity were performed (Chi-square and I-square statistic) between comparable trials in order to assess whether consistent findings occurred among pooled studies. All statistical

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Excluded articles The search strategy and additional searching resulted in a list of 25 955 potentially relevant articles. After exclusion of articles at both title and abstract screening, a total 41 full-text articles were assessed for eligibility. Thirtyfour articles did not meet the inclusion/exclusion criteria and were excluded from the review. Excluded studies were due to failure to meet criterion for age (19), uncontrolled or inadequately controlled (14), or no relevant outcome measures (1). Included articles Four articles met the eligibility criteria and therefore were eligible for analysis. An additional two articles retrieved by the search involved either a participant subgroup or the same participant group reported in a previously published included article. Fiatarone et al. (1999) included a subgroup of the Fiatarone et al. (1994) participants, which reported muscle cross-sectional area (CSA); the 1999 article, however, reported a different but relevant outcome measure (muscle fiber size). Sipilä et al. (1997) included the same participants as Sipilä and Suominen (1995) which reported muscle CSA. However, the 1997 article reported muscle fiber characteristics including fiber size, also relevant to this review. The additional outcome data reported in Fiatarone et al. (1999) and Sipilä et al. (1997) were reported in this review, Fiatarone et al. (1994) and Fiatarone et al. (1999) were referred to as one study, as were Sipilä and Suominen (1995) and Sipilä et al. (1997). Methodological quality Only one trial (Fiatarone et al., 1994) was considered of moderate to high quality scoring 7 on the PEDro scale, while the remaining three trials scored below 6 out of 10, (scores were from 3 to 5). Study participants A summary of the included studies is provided (Table 1) containing participant characteristics, details of the intervention and control, outcome measures and results and PEDro score. The total number of participants in the included studies was 143, and all were aged 75 years or over with a mean age range between 76.2 and 89.2 years. The mean percentage of female participants in the

Hypertrophic ability of older muscle Records identified through database searching (n = 25906)

Additional records identified through other sources (n = 49)

Records after duplicates removed (n = 25461)

Records screened (n = 25461) Titles excluded (n = 25216) Total abstracts screened (n = 245) Abstracts excluded (n = 204) Full-text articles assessed for eligibility (n = 41) Full text articles excluded, with reasons (n = 35) Articles included in qualitative synthesis (n = 6)

Studies included in quantitative synthesis (metaanalysis) (n = 4)

Articles excluded from meta-analysis due to studies reported by more than one article (n = 2)

Fig. 1. Study flow chart. Flow diagram depicting the number of articles present at each stage of selection including identification, screening, eligibility and inclusion. Adapted from Moher et al. (2009).

intervention groups was 85% compared with 89% of the control groups. Participants were defined as healthy on the basis of evidence of meeting predefined health inclusion/exclusion criteria.

ity was the intervention implemented in the remaining study although walking was the main mode of activity; aerobic, strength, flexibility and balance training were also included (Goodpaster et al., 2008).

Intervention

Outcome measures

The physical training intervention varied considerably between studies: The intervention group studied by Fiatarone et al. (1994) participated in high intensity [80% of one-repetition maximum (1-RM)] PRT of the hip and knee extensors 3 days per week for 10 weeks and in the study by Sipilä and Suominen (1995), the intervention groups trained for 16 weeks at either high intensity (60–75% of 1-RM) PRT of the quadriceps femoris, hamstrings and calf muscles or endurance training which included track walking twice a week and step aerobics once a week. In Machado et al. (2010), the intervention group participated in 10 weeks of lower body training using a vibration platform. This consisted of static and dynamic exercises including half squat (knee angle between 120° and 130°), deep squat (knee angle 90°) and wide stance squat and calves. The intervention was described as progressive in two of four studies (Sipilä & Suominen, 1995; Machado et al., 2010), most commonly by increasing the 1-RM during exercise. Physical activ-

Four of four studies reported change (three positive and one negative) in CSA of either the total thigh or quadriceps (knee extensor) muscles (Fiatarone et al., 1994; Sipilä & Suominen, 1995; Goodpaster et al., 2008; Machado et al., 2010) and three of four of these studies also measured changes in muscle strength (Fiatarone et al., 1994; Goodpaster et al., 2008; Machado et al., 2010). In addition two studies also included measurement of CSA of type I and II muscle fibers (Fiatarone et al., 1999; Sipilä et al. 1997). Fiatarone et al. (1999) measured changes in lower body strength and muscle fiber (type I and II) CSA. Sipilä et al. (1997) measured only changes in muscle fiber (type I and II) CSA. Findings of the review The absolute and relative (percentage) changes in muscle size and muscle strength outcomes reported by the included studies are summarized in Table 2.

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26

22

20 13

13 12

12

Control

Training

Control Training

Control Training

Control

54% 77%

70% 100% 100% 100%

89.2 ± 0.8

76.7 ± 1.0

77.4 ± 1.0 79.3 ± 7.3

76.2 ± 8.4 Range 76 to 78 years

100%

64%

86.2 ± 1 (72–95)

Range 76 to 78 years

Female

Mean Age (range) years

Instructed to continue daily routines

High-intensity (80% 1-RM) PRT of hip and knee extensors 3 × 8 sets of 8 reps (2-min rest) 45 min per session, 3 day/week. Total duration 10 weeks Allowed aerobic/ flexibility exercises and board games, crafts, group discussion for 10 weeks Aerobic, strength, flex & balance training – walking main mode of activity. Total duration 1 year. Weeks 1–8 = 3 × 40–60 min center-based sessions/week Weeks 9–24 = 2 × center- and home-based sessions/week Weeks 25-end = min 5 × home-based sessions/week Health education 1 session/ week during weeks 1–26 then 1 session/ month WBV using vibration platform. Training volume increased by increasing session duration, no. of series of one exercise or no. of different exercises. Training intensity increased by increasing amplitude or frequency of vibration. Total duration 10 weeks Participants requested not to change lifestyle or engage in any activity Strength: leg press, leg extension curl, leg flexion curl and calf raise. Three to four sets of 8–10 reps with 30 s rest between sets. Intensity = 60% 1-RM week 1, = 70% 1-RM week 2–12 and = 75% 1-RM week 13–16 Endurance: track walking 2 × week, step aerobics 1 × week. Total duration 16 weeks

Exposure

Endurance 89% –

– Strength 65%

70% 94.8%

A = 66% T = 69% M = 56%

100%

90%

Adherence

Gross CSA Fiber CSA

Gross CSA

Gross CSA Fiber CSA

Gross CSA Fiber CSA

Outcome measure

4/10

5/10

5/10

7/10

PEDro score

n, number of participants; PRT, progressive resistance training; 1-RM, 1 repetition maximum; CSA, cross-sectional area; MVC, maximal voluntary contraction; WBV, whole body vibration; VM, vastus medialis; VL, vastus lateralis; BF, biceps femoris; MVIC, maximal voluntary isometric contraction; sEMG, surface electromyographic activity; PRT, progressive resistance training. a; n = 55 enrolled but n = 4 did not complete study. b; n = 29 enrolled but n = 3 did not complete. c; n = 31 enrolled but n = 7 did not complete. – represents a measurement not reported by the study; Fiatarone et al. (1994) includes Fiatarone et al. (1999). Sipilä and Suominen (1995) include Sipilä et al. (1997).

Sipilä & Suominen, 1995, Sipilä et al. 1997 n = 24c

Machado et al. 2010 n = 26b

Goodpaster et al. 2008 n = 42

25

Training

Fiatarone et al. 1994, 1999 n = 51a

n

Participants

Group

Study

Table 1. Summary of the included studies

Stewart et al.

Hypertrophic ability of older muscle Table 2. Absolute and relative (percentage) changes in muscle size and muscle strength outcomes

Study

Outcome

Measurement tool and unit

Intervention

Control

Absolute change Fiatarone et al. 1994 (Including Fiatarone et al., 1999) Goodpaster et al. 2008

Thigh muscle area Muscle strength (R knee) Type I Fiber CSA Type II Fiber CSA Thigh muscle CSA Quadriceps muscle mass Isokinetic strength

Machado et al. 2010

Muscle CSA MVIC

Sipilä & Suominen, 1995 (Including Sipilä et al., 1997)

Total thigh lean CSA

VL VM BF

CT cm2 Dynamometry 1-RM – kg Biopsy μm2 CT cm2 CT Dynamometry N·m−1

CT mm2 Leg press machine – N cm2

% Change

CT cm2

Lean Tissue CSA

Type I Fiber Area Type IIa Fiber Area

Q H K L Q H K L

Biopsy μm2

% Change

0.9 ± 1.7

2.0 ± 2.5

−0.4 ± 1.9

−0.9 ± 2.9

4.9 ± 0.6

156.1 ± 29.3

0.1 ± 0.6

18.3 ± 29.1

133 −241 −2.92

4.06 −9.55 −3.0 ± 1.0

−867 −296 −3.78

−18.02 −15.95 −4.0 ± 1.0

–

−3.0 ± 1.0 −1.5

– −17.25

−1.0 ± 1.0 −21.6 ± 1.0

28.2 12.0 23.0 10.0

5.0 0.4 3.3 0.013

−6.25 60°/s 120°/s 180°/s 44.0 59.3 113.5 350.0

– – –

1.5

2.0 0.3 −0.5 2.6 2.3 0.6 0.4 2.9 1146 142

47 45 44 8.8 2.3 15.6 38.8 ± 18.3 1.5

Strength Muscle CSA

Absolute change

−2.4

Endurance 4.5 1.1 −0.9 4.9 5.8 2.8 0.9 5.8 34.2 7.3

0.9 0.4 −1.1 1.5 0.6 0.4 −0.9 1.3 206 18

−2.6

Control 2.0 1.5 −1.9 2.8 1.5 1.8 −1.9 2.7 5.4 0.8

0.1 0.7 −0.6 0.8 −0.1 0.8 −0.5 0.8 −596 −452

0.2 2.9 −1.1 1.6 −0.3 3.9 −1.1 1.7 −16.6 −17.1

– represents a measurement not reported by the study; CSA, cross-sectional area; VL, vastus lateralis; VM, vastus medialis; BF, biceps femoris; MVIC, maximal voluntary isometric contraction; Q, quadriceps; H, hamstrings; K, knee extensor compartment; L, lower leg muscles.

Muscle size Muscle size increased in three of four studies (Fiatarone et al., 1994; Sipilä & Suominen, 1995; Machado et al., 2010), from 1.5% to 15.6%. In the remaining study, muscle size decreased by 3% and 4% in the control and intervention groups, respectively (Goodpaster et al., 2008). Thigh muscle CSA increased by 2% compared with −0.9% in the control group of one study (Fiatarone et al., 1994). In the study by Sipilä and Suominen (1995), total thigh lean CSA increased by 1.5% in the intervention group compared with the control groups 2.6% decrease (Sipilä & Suominen, 1995). The intervention group also demonstrated increases in muscle CSA of the quadriceps (4.5%), hamstrings (1.1%) and lower leg muscles (4.9%) but a loss of 0.9% of the knee extensor compartment. The control group demonstrated changes in the respective muscle of 0.2%, 2.9%, 1.6% and −1.1%. In the remaining study (Machado et al., 2010), vastus lateralis and biceps femoris CSA increased significantly by 8.8% and 15.6%

in the intervention and 5.0% and 3.3% in the control groups, respectively while the vastus medialis increased, but not significantly, by 2.3% in the intervention group compared with 0.4% in the control group. Data from three out of four studies reporting changes in thigh muscle CSA could be pooled in a meta-analysis (Fiatarone et al., 1994; Sipilä & Suominen 1995; Goodpaster et al., 2008). Analysis demonstrated that very elderly people participating in physical training (n = 59) compared with those in control groups participating in no physical training (n = 57) achieved a MD (fixed) of 2.31 cm2 (95% CI 0.62 to 4.00; P = 0.008) (Fig. 2). This corresponded with a mean percentage increase of thigh muscle CSA of 0.2%. Since the study by Goodpaster et al. (2008) differed markedly from the others in terms of both protocol and results, a secondary meta-analysis was conducted omitting this study. As expected, heterogeneity was reduced and the MD (fixed) increased to 3.34 cm2 (95% CI 1.04 to 5.65; P = 0.005) equating to a mean percentage increase of 1.75% (Fig. 3).

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Stewart et al.

Fig. 2. Thigh muscle cross sectional area. Forest plot illustrating the mean difference (MD) in thigh muscle cross-sectional area between the intervention and control group of the three appropriate studies. The forest plot illustrates the MD of each individual study, shown as filled square symbols centered on the MD with extending horizontal lines indicating the 95% confidence intervals (CI). The different sized boxes represent the weight given to the study based on its standard deviations and number of participants. The overall MD is presented as a filled diamond whose extremities show the 95% CI.

Fig. 3. Thigh muscle cross sectional area. Forest plot illustrating the mean difference in thigh muscle cross-sectional area between the intervention and control group of the two studies.

Fig. 4. Muscle strength. Forest plot illustrating the standardized mean difference in muscle strength between the intervention and control group of the three appropriate studies.

Muscle strength There was wide variability in the methods and techniques used to measure muscle strength, including a concentric 1-RM, maximal voluntary isometric contraction and maximal isokinetic strength testing. Two of the studies reported a statistically significant strength increase after physical training and another reported a decrease of 1.5% in the intervention group in comparison with a 21.6% decrease in the control group (Goodpaster et al., 2008). Strength increases in the intervention groups of the two studies were 156.1% and 38.8%, respectively in comparison with the 18.3% and 0% increases in the control groups (Fiatarone et al., 1994; Machado et al., 2010). Three studies reporting changes in muscle strength in response to physical training had sufficient data to be

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pooled for meta-analysis (Fiatarone et al., 1994; Goodpaster et al., 2008; Machado et al., 2010). Analysis demonstrated that very elderly people participating in physical training (n = 60) compared with the control group participating in no physical training (n = 59) achieved a SMD (fixed) of 1.04 (95% CI: 0.65 to 1.43; P < 0.00001) (Fig. 4). A SMD of 1.04 is suggestive of a large and positive effect on muscle strength (Higgins & Green, 2008).

Muscle fiber CSA Muscle fiber CSA was included as an outcome measure in two of four studies. The intervention groups reported increases in type I fiber CSA of 4% and 34.2%, respectively (Sipilä et al. 1997; Fiatarone et al., 1999), while

Hypertrophic ability of older muscle the control groups reported decreases in CSA of 18.02% and 16.6%. Type II fiber CSA decreased by 9.55% and 15.95% in the intervention and control groups of one study (Fiatarone et al., 1999), and increased by 7.3% in the intervention group in comparison with a 17.1% decrease reported in the control group (Sipilä et al., 1997). Discussion The aim of this review was to assess whether a physical training intervention has the ability to elicit a significant hypertrophic response in the muscle of very elderly (> 75 years) men and women. This review revealed a surprising dearth of information relating to the hypertrophic ability of very elderly human muscle. Only four controlled studies including only 185 older adults were found reporting changes in gross muscle of muscle fiber CSA. A PEDro score of > 6 was demonstrated in only one study (Fiatarone et al., 1994). Three studies reported a significant effect of physical training on muscle size, from 1.5% to 15.6%; although with the exception of Machado et al. 2010 all differences were below 4.9%. The intervention implemented by Machado et al. (2010) utilized whole body vibration (WBV) training and thus differed from the more conventional training programs reported in the other studies. The WBV intervention elicited the greatest increase in muscle size, in which the cross sectional area of the biceps femoris increased by 15.6%. This heightened hypertrophic response could, in part, be a result of the eccentric component employed by the WBV training as the vibration acts to oppose the exercise movement. Training programs in younger and older adults incorporating eccentric exercises have been shown to greater responsiveness in terms of size and strength compared with more traditional regimes (Hortobágyi & DeVita, 2000; LaStayo et al., 2003; Norrbrand et al., 2008), suggesting that the provision of eccentric overload can act as a potent enhancer of the hypertrophic response generated by resistance training and (along with a greater isometric load employed in the study protocol) may explain the increased hypertrophy in older participants reported by Machado et al. (2010). One study (Goodpaster et al., 2008) actually reported a negative effect of physical training on muscle size (and strength), and these atypical results may have been a consequence of the low (< 70%) adherence rates and the training intervention implemented in the study, which involved 12 months of a combination of primarily walking exercise complemented by strength, stretching and balance exercises. Given the inevitable age related decline in muscle function, the study duration may have been a confounding factor, although the outcome for muscle strength for the intervention group was more favorable compared with the controls. Meta-analysis

demonstrated that for the randomized studies measuring the change in total thigh CSA (Fiatarone et al., 1994; Sipilä & Suominen, 1995; Goodpaster et al., 2008) the intervention group experienced an MD of 2.31 cm2 or 0.2% increase in muscle size in comparison with controls. Exclusion of the Goodpaster et al. (2008) results from the meta-analysis resulted in a mean increase in muscle size of 3.34 cm2 or 1.75%. However, this magnitude of change is still less than the coefficient of variation of measurements of muscle CSA using magnetic resonance imaging (MRI)/computed tomography (CT) (MacDonald et al., 2011). The two of four studies including muscle fiber CSA as an outcome measure were not in complete agreement. Generally, in younger adults, PRT elicits greater increases in the size of type II fibers compared with type I fibers (Andersen & Aagaard, 2000). However, studies of very elderly adults report disparate results as to which muscle fibers hypertrophy in response to training, and others report no change in fiber area (Slivka et al., 2008). In this review, type I fibers hypertrophied in response to physical training in both studies (Fiatarone et al., 1999; Sipilä et al. 1997) by 4.06% and 34.2%, respectively while type II fiber area increased in one study (Sipilä et al. 1997) by 7.3% and decreased by 9.55% in the other study (Fiatarone et al., 1999). Therefore, type I fibers appear to hypertrophy more than type II fibers as the mean increase in type I fiber area was 19.13% in comparison with the 1.13% decrease in type II fiber area. This finding should be interpreted with caution however, due to the relative lack of data. The three of four studies reporting an increase in muscle size after training also reported a significant increase in muscle strength which, as in younger adults, exceeded the increases in muscle size. The intervention groups demonstrated increases in muscle strength from 38.8% to 156%, equivalent to a SMD of 1.04. However, two of three of the studies measuring muscle strength did so by measuring the 1-RM (Fiatarone et al., 1994; Goodpaster et al., 2008) rather than muscle force generating capacity directly (Machado et al., 2010). Nevertheless, an improvement of 38.8% is indicative that physical training can increase muscle strength in very elderly people and in the absence of appreciable hypertrophy. Although this review was not designed to compare the responsiveness of old with young muscle in response to physical training, the search found two studies (Raue et al. 2009; Greig et al. 2011) which showed a “blunting” of the adaptive response experienced by very elderly women, (i.e., very small non-significant increases in muscle size and strength compared with larger and statistically significant increases in younger women) in response to physical training. Consistent with this, another study has shown that older men show an attenuated recovery of muscle fiber area and rapid force generating capacity (but not maximal isometric or dynamic strength) after a period of immobilization; Hvid et al.

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Stewart et al. 2010). These data support the theory that increasing age is associated with a reduction of skeletal muscle plasticity although this review has shown that very elderly muscle retains the capacity to respond to a hypertrophic stimulus. Perspective Physical training in the form of resistance training has the ability to elicit hypertrophy in very elderly people although the magnitude is very small, i.e., 1.75% increase from baseline (in those positive studies included in the meta analysis), which is arguably within the measurement error of MRI/CT. Physical training also has the ability to

significantly increase muscle strength in very elderly participants with a moderate effect size. These positive effects could have significant implications for the management of sarcopenia. In particular WBV training has been suggested to have important therapeutic potential as it could be implemented with elderly people unable to perform standard exercise regimes yet still elicit improvements in muscular performance. The disparity between the increases in size and strength would suggest that, as in younger adults, muscle hypertrophy is not necessary to elicit functional gains in response to training. Key words: progressive resistance training, sarcopenia, muscle size.

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statement. BMJ 2009: 339: 332–336. doi: 10.1136/bmj.b2535. Norrbrand L, Fluckey JD, Pozzo M, Tesch PA. Resistance training using eccentric overload induces early adaptations in skeletal muscle size. Eur J Appl Physiol 2008: 102: 271–281. PEDro. 1999). PEDro Scale. URL: http://www.pedro.org.au/english/ downloads/pedro-scale/. [Accessed March 2012]. RevMan. Review Manager (RevMan) [Computer program]. Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011. Rosenberg IH. Sarcopenia: origins and clinical relevance. Clin Geriatr Med 2011: 27 (3): 337–339. Seynnes OR, Boer M, Narici MV. Early skeletal muscle hypertrophy and architectural changes in response to high-intensity resistance training. J Appl Physiol 2007: 102: 368–373. Sipilä S, Elorinne M, Alen M, Suominen H, Kovanen V. Effects of strength and endurance training on muscle fibre characteristics in elderly women. Clin Physiol 1997: 17: 459–474. Sipilä S, Suominen H. Effects of strength and endurance training on thigh and leg muscle mass and composition in elderly women. J Appl Physiol 1995: 78: 334–340. Skelton DA, McLaughlin AW. Training functional ability in old age. Physiotherapy 1996: 82: 159–167. Slivka D, Raue U, Hollon C, Minchev K, Trappe S. Single muscle fiber adaptations to resistance training in old (>80 yr) men: evidence for limited skeletal muscle plasticity. Am J Physiol Regul Integr Comp Physiol 2008: 295: 273–280. Svanborg A. The health of the elderly population: results from longitudinal

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References to studies excluded from the review (with main reason for exclusion) Cancela JM, Varela S, Ayán A. Effects of high intensity training on elderly women: a pilot study. Phys Occup Ther Geriatr 2008: 27: 160–169. (did not meet age criterion; uncontrolled). Cannon J, Kay D, Tarpenning KM, Marino FE. Comparative effects of resistance training on peak isometric torque, muscle hypertrophy, voluntary activation and surface EMG between young and elderly women. Clin Physiol Funct 2007: 27: 91–100. (did not meet age criterion). Cress ME, Conley KE, Balding SL, Hansen-Smith F, Konczak J. Functional training: muscle structure, function, and performance in older women. J Orthop Sports Phys Ther 1996: 24: 4–10. (did not meet age criterion). Evans WJ. High-velocity resistance training for increasing peak muscle power in elderly women. Clin J Sport Med 2003: 13: 66. (did not meet age criterion). Fiatarone MA, Marks EC, Ryan ND, Meredith CN, Lipsitz LA, Evans WJ. High-intensity strength training in nonagenarians. Effects on skeletal muscle. JAMA 1990: 263: 3029–3034. (uncontrolled). Fiatarone MA, O’Neill EF, Doyle N, Clements KM, Roberts SB, Kehayias JJ, Lipsitz LA, Evans WJ. The Boston FICSIT study: the effects of resistance training and nutritional supplementation on physical frailty in the oldest old. J Am Geriatr Soc 1993: 41: 333–337. (protocol only). Frontera WR, Hughes VA, Krivickas LS, Kim SK, Foldvari M, Roubenoff R. Strength training in older women: early and late changes in whole muscle and single cells. Muscle Nerve 2003: 28: 601–608. (did not meet age criterion). Greig CA, Gray C, Rankin D, Young A, Mann V, Noble B, Atherton PJ. Blunting of adaptive responses to resistance exercise training in women over 75y. Exp Gerontol 2011: 46: 884–890. (inadequately controlled according to criterion specified in our review). Grimby G, Aniansson A, Hedberg M, Henning GB, Grangård U, Kvist H. Training can improve muscle strength and endurance in 78- to 84-yr-old men. J Appl Physiol 1992: 73: 2517–2523. (uncontrolled).

Harridge SD, Kryger A, Stensgaard A. Knee extensor strength, activation, and size in very elderly people following strength training. Muscle Nerve 1999: 22: 831–839. (uncontrolled). Hasten DL, Pak-Loduca J, Obert KA, Yarasheski KE. Resistance exercise acutely increases MHC and mixed muscle protein synthesis rates in 78-84 and 23-32 yr olds. Am J Physiol Endocrinol Metab 2000: 278: 620–626. (no measure of change of muscle size). Kryger AI, Andersen JL. Resistance training in the oldest old: consequences for muscle strength, fibre types, fibre size and MHC isoforms. Scand J Med Sci Sports 2007: 17: 422–430. (inadequately controlled according to criterion specified in our review). Kubo K, Ishida Y, Suzuki S, Komuro T, Shirasawa H, Ishiguro N, Shukutani Y, Tsunoda N, Kanehisa H, Fukunaga T. Effects of 6 months of walking training on lower limb muscle and tendon in elderly. Scand J Med Sci Sports 2008: 18: 31–39. (did not meet age criterion). LaStayo P, McDonagh P, Lipovic D, Napoles P, Bartholomew A, Esser K, Lindstedt S. Elderly patients and high force resistance exercise – a descriptive report: can an anabolic, muscle growth response occur without muscle damage or inflammation? J Geriatr Phys Ther 2007: 30: 128–134. (uncontrolled). Lexell J, Downham DY, Larsson Y, Bruhn E, Morsing B. Heavy-resistance training in older Scandinavian men and women: short- and long-term effects on arm and leg muscles. Scand J Med Sci Sports 1995: 5: 329–341. (did not meet age criterion). Lexell J, Robertsson E, Stenström E. Effects of strength training in elderly women. JAMA 1992: 40: 190–191. (did not meet age criterion; uncontrolled). Lovell DI, Cuneo R, Gass GC. Can aerobic training improve muscle strength and power in older men? J Aging Phys Activ 2010: 18: 14–26. (did not meet age criterion). McCartney N, Hicks AL, Martin J, Webber CE. Long-term resistance training in the elderly: effects on dynamic strength, exercise capacity, muscle, and bone. J Gerontol A Biol Sci Med Sci 1995: 50: B97–104. (did not meet age criterion).

Melov S, Tarnopolsky MA, Beckman K, Felkey K, Hubbard A. Resistance exercise reverses aging in human skeletal muscle. PLoS ONE 2007: 2 (5): e465. (did not meet age criterion). Moritani T, deVries HA. Potential for gross muscle hypertrophy in older men. J Gerontol 1980: 35: 672–682. (did not meet age criterion). Morse CI, Thom JM, Mian OS, Muirhead A, Birch KM, Narici MV. Muscle strength, volume and activation following 12-month resistance training in 70-year-old males. Eur J Appl Physiol 2005: 95: 197–204. (did not meet age criterion). Ogawa K, Sanada K, Machida S, Okutsu M, Suzuki K. Resistance exercise training-induced muscle hypertrophy was associated with reduction of inflammatory markers in elderly women. Mediators Inflamm 2010: 2010: 171023. doi: 10.1155/2010/ 171023. (uncontrolled). Parente V, D’Antona G, Adami R, Miotti D, Capodaglio P, De Vito G, Bottinelli R. Long-term resistance training improves force and unloaded shortening velocity of single muscle fibres of elderly women. Eur J Appl Physiol 2008: 104: 885–893. (uncontrolled). Raue U, Slivka D, Minchev K, Trappe S. Improvements in whole muscle and myocellular function are limited with high-intensity resistance training in octogenarian women. J Appl Physiol 2009: 106: 1611–1617. (inadequately controlled according to criterion specified in review). Sipilä S, Suominen H. Knee extension strength and walking speed in relation to quadriceps muscle composition and training in elderly women. Clin Physiol 1994: 14: 433–442. (did not meet age criterion). Slivka D, Raue U, Hollon C, Minchev K, Trappe S. Single muscle fiber adaptations to resistance training in old (>80 yr) men: evidence for limited skeletal muscle plasticity. Am J Physiol Regul Integr Comp Physiol 2008: 295: 273–280. (uncontrolled). Sullivan DH, Roberson PK, Smith ES, Price JA, Bopp MM. Effects of muscle strength training and megestrol acetate on strength, muscle mass, and function in frail older people. JAMA 2007: 55:

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Stewart et al. 20–28. (inadequately controlled according to criterion specified in review). Taaffe DR, Pruitt L, Pyka G, Guido D, Marcus R. Comparative effects of highand low-intensity resistance training on thigh muscle strength, fiber area, and tissue composition in elderly women. Clin Physiol 1996: 16: 381–392. (did not meet age criterion). Takano Y, Haneda Y, Maeda T, Sakai Y, Matsuse H, Kawaguchi T, Tagawa Y, Shiba N. Increasing muscle strength and mass of thigh in elderly people with the hybrid-training method of electrical stimulation and volitional contraction. Tohoku J Exp Med 2010: 221: 77–85. (did not meet age criterion). Tanton LC, Cappaert TA, Gordon PM, Zoeller RF, Angelopoulos TJ, Price TB, Thompson PD, Moyna NM, Seip

RL, Pescatello LS, Devaney JM, Gordish-Dressman H, Hoffman EP, Visich PS. Strength, size, and muscle quality in the upper arm following unilateral training in younger and older males and females. Clin Med Insights Arthritis Musculoskelet Disord 2009: 2: 9–18. (did not meet age criterion). Tsourlou T, Benik A, Dipla K, Zafeiridis A, Kellis S. The effects of a twenty-four-week aquatic training program on muscular strength performance in healthy elderly women. J Strength Cond Res 2006: 20: 811–818. (did not meet age criterion). Verschueren SM, Bogaerts A, Delecluse C, Claessens AL, Haentjens P, Vanderschueren D, Boonen S. The effects of whole-body vibration training and vitamin D supplementation on muscle strength, muscle mass, and

Appendix MEDLINE Search Strategy MEDLINE (Ovid) search strategy 1 2 3 4 5 6 7 8 9 10 11 12 13 14

15

16 17 18

19 20 21

exp exercise/ Exercise Test/ Physical Fitness/ exp exercise therapy/ exercise movement techniques/ or dance therapy/ or tai ji/ or yoga/ isometric contraction/ isotonic contraction/ “physical education and training”/ Resistance training/ exp sports/ Locomotion/ Sports equipment/ Walking/ (physical adj3 (exercise* or exertion* or endurance* or therap* or activit* or conditioning or fitness or train*)).tw. (exercise adj3 (train* or intervention* or protocol* or program* or therap* or regim* or activit* or chronic)).tw. (fitness adj3 (train* or intervention* or protocol* or program* or therap* or activit* or regim*)).tw. ((training or conditioning) adj3 (intervention* protocol* or program* or activit* or regim*)).tw. ((endurance or aerobic or cardio*) adj3 (fitness or train* or intervention* or protocol* or program* or therap* or activit* or regim*)).tw. (muscle strengthening or progressive resist*).tw. ((weight or strength* or resistance) adj3 (train* or condition* or exercise* or lift*)).tw. ((isometric or isotonic or dynamic or eccentric or concentric or pleiometric or myometric) adj (action* or contraction* or exercise*)).tw.

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bone density in institutionalized elderly women: a 6-month randomized, controlled trial. J Bone Miner Res 2011: 26: 42–49. (inadequately controlled according to criterion specified in review). Villareal DT, Holloszy JO. DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. Am J Physiol Endocrinol Metab 2006: 291: 1003–1008. (did not meet age criterion). Yarasheski KE, Pak-Loduca J, Hasten DL, Obert KA, Brown MB, Sinacore DR. Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men >/=76 yr old. Am J Physiol 1999: 277: 118–125. (inadequately controlled according to criterion specified in review).

22 (sport* or recreation* or leisure or bowling or cycling or bicycl* or rowing or treadmill* or running or circuit training or swim* or walk* or dance* or dancing or tai ji or tai chi or yoga).tw. 23 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 24 Muscles/ph 25 Muscle, Skeletal/ph 26 Deltoid Muscle/ph 27 Neck Muscles/ph 28 Pectoralis Muscles/ph 29 Psoas Muscles/ph 30 Quadriceps Muscles/ph 31 muscle strength/ or hand strength/ or pinch strength/ 32 Hypertrophy/ 33 exp Skeletal Muscle/ 34 32 and 33 35 (muscle* adj2 (mass or size or strength or thick* or power or growth or enlarge* or area or volume or hypertrophy)).tw. 36 (muscle fibre adj2 (size* or area* or hypertrophy)).tw. 37 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 34 or 35 or 36 38 aged/ or “aged, 80 and over”/ or frail elderly/ 39 aging/ or longevity/ 40 (old* adj (adult* or age* or people or person* or population*)).tw. 41 (elderly or old* or?enarian or aged or ag?ing or senior* or geriatric* or frail).mp. or “old age”.tw. 42 38 or 39 or 40 or 41 43 23 and 37 and 42 44 limit 43 to humans