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A Novel Low-Mass, High-Repetition Approach to Improve Function in Older Adults


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Medicine & Science in Sports & Exercise: May 2018 - Volume 50 - Issue 5 - p 1005-1014
doi: 10.1249/MSS.0000000000001518


The proportion of people worldwide older than 65 yr is estimated to grow from 8% in 2010 to 16% by 2050 (1). Although it is clear people are living longer, the quality of life during those extra years is not evident (2). Enabling older individuals to lead long and healthy lives may actually reduce health care costs and encourage continued productivity and societal contributions (3).

In older adults, low levels of physical activity are associated with slower gait speeds (4), poorer activities of daily living function (5), and more reported “unhealthy days” (6). However, prospective cohort studies suggest that engaging in physical activity may reduce the risks of incurring functional limitations and disability (7–9). Similarly, the risk of losing independence is 30% and 50% lower for moderately and highly fit older individuals, respectively, when compared with a low-fit group (10).

A V˙O2peak of between 15 and 22 mL·kg−1·min−1 is associated with an independent lifestyle (11–13), with a steep drop in the probability of remaining “functionally independent” in those below this range (11). When considering maintained independence, these low-fit individuals (<20 mL·kg−1·min−1) may also produce best return on investment from an exercise intervention. Currently, however, the optimal amounts, types, and dosages of physical activity and/or exercise required are unclear. A systematic review of prospective aerobic training (AT) studies suggests moderate- to vigorous-intensity (11.6–14.7 mL·kg−1·min−1) activities may be required to increase cardiorespiratory fitness (8), but for most individuals at risk for losing functional independence, this intensity of physical activity is beyond their capabilities. Similarly, despite data that resistance training (RT) increases in physical performance, there is limited evidence (excluding clinical populations) regarding a reduction in the risk of functional limitations (8,14). Again higher-intensity progressive training may be most effective (15) but difficult to perform for many individuals.

The LIFE study (7) (n = 1635) consisted of a 2.6-yr moderate-intensity physical activity program focused predominantly on walking (but complimented by lower body strengthening, balance, and flexibility exercises) versus an education only program. The exercise intervention demonstrated that 30.1% rate of incident major lower extremity mobility disability (defined as an inability to walk 400 m) significantly reduced from 35.5% in the education only program. However, the number that needed treatment with exercise to prevent an additional negative outcome was 18.5 (7). In addition, although the intervention increased lower body physical performance (assessed by the three test Short Physical Performance Battery) (16), no differences were observed in handgrip strength and no data were collected on upper body functional outcomes.

Unfortunately, current guidelines for older individuals (17) provide little insight into how to optimally incorporate the principles of specificity, overload, and progression into an exercise regimen to maximize functional benefits. The guidelines recommend a well-rounded, whole-body training program and implementation typically starts with low- to moderate-intensity AT, with a gradual increase in time and intensity with RT added later in the program. This fails to address the discrepancies between the need for higher-intensity workloads for greater functional gains and the difficulty in tolerating this intensity for those at risk of losing independence.

As outlined in the Baltimore Longitudinal Aging Study, the accelerated decline in V˙O2peak after the age of 65 yr is primarily due to peripheral tissue mechanisms (18). Consequently, we designed the Peripheral Remodeling through Intermittent Muscular Exercise (PRIME) training study. PRIME targets functional groups of peripheral muscle tissues, with a low-mass, high-repetition/duration modality (AT + RT) that induces relatively low central cardiovascular strain and can be tolerated by older individuals at risk for losing functional independence.

The objective of this study was to compare the effectiveness of an initial 4 wk of PRIME training compared with initial AT training, when followed by 8 wk AT + RT (as recommended by the American College of Sports Medicine/American Heart Association guidelines) (17) on measures of physical fitness (V˙O2peak, 1 repetition maximal [1RM] strength) and physical function (Senior Fitness Test [SFT] scores) in older individuals at risk for losing functional independence.


Study design

A complete description of the “PRIME” design and methods have been published (the intervention was initially named “RSTS”) (19). In brief, the study was a two-arm, prospective randomized clinical trial with participants randomized, in a 1:1 ratio, to 4 wk of either standard AT or PRIME training (phase 1, detailed below). This was followed by 8 wk of a progressive whole-body AT + RT assigned to all participants (phase 2). Our study procedures are outlined in a CONSORT schematic in Figure 1. The research protocol was reviewed and approved annually by the Duke University Medical Center (Durham, NC) and Pennington Biomedical Research Center (PBRC, Baton Rouge, LA) Institutional Review Boards. Informed consent was obtained from all participants before any assessments.

CONSORT schematic of the PRIME Study. Thirty-eight subjects in each treatment arm had complete data sets and were included in the final analysis. *Spousal randomizations were when couples wished to be enrolled in the study together and desired to be guaranteed in the same intervention group. In these cases, to adhere to the randomization schedule, we only included the data from the primary subject, who was determined at random. This “allocation” was unknown to the study staff and the participants.

To ensure the fidelity of approach between sites, we generated standard operating procedures manuals for all testing and training protocols. The individuals that were primarily responsible for patient training and testing spent time observing at the “sister” institution to ensure accurate duplication of protocol implementation. We also scheduled regular study conference calls to allow standardization of responses to any other issues that arose.

Participants and enrollment process

Our goal was to enroll participants older than 70 yr at risk for losing functional independence based on a peak cardiorespiratory capacity (V˙O2peak) of 15–20 mL·kg−1·min−1. This range was selected based on previous work by Cress and Meyer (11), who found it was associated with a threshold physical function score believed to accurately predict the risk for losing independence. The recruitment process involved phone screen interviews to determine participant eligibility. Qualifying participants then attended an orientation visit, including an explanation of study procedures, signing an informed consent, a review of medical history, and a 6-min walk test. Using previous data from the Louisiana Healthy Aging Study (n = 286, unpublished), which measured both V˙O2peak and 6-min walk distance, we determined that subjects who could walk between 200 and 450 m in a standard 6-min walk test should have a V˙O2peak of approximately 15–20 mL·kg−1·min−1 and could proceed to the baseline testing visits.

Exclusion criteria included recent (3 months) changes in medications, current smoking, oxygen dependency, usage of fixed rate pacemakers or defibrillator, uncontrolled hypertension or diabetes, history of unstable angina, American Heart Association Class D, or New York Heart Association Class III or IV heart failure, and positive ECG changes or angina during the maximal-graded cardiopulmonary exercise test (CPET). If a volunteer met inclusion/exclusion, they initiated baseline testing followed by the randomized assignment to one of the pretreatment (phase 1) conditions.

Baseline testing assessments (TA0) consisted of a repeat medical history, CPET (Parvo Medics, Sandy, UT) with 12-lead ECG and V˙O2peak assessment, 1RM strength testing, and SFT assessments (19). Participants were randomized in phase 1 to (a) an initial 4 wk of AT or (b) an initial 4 wk of PRIME (described below) using a randomized block design with separate computer-generated blocks for white women, white men, minority women, and minority men for each of the two study sites. After the completion of phase 1, participants completed an intermediate testing assessment (TA1), and then all participants entered phase 2, which consisted of 8 wk of a “traditional” combined program consisting of both AT and RT performed by all participants based on the American College of Sports Medicine (ACSM)/American Heart Association 2007 physical activity recommendations for older adults (17) and also consistent with the 2008 U.S. Department of Health and Human Services Physical Activity Guidelines (20). After the 8 wk of phase 2 training, participants completed a final follow-up visit (TA2). TA1 and TA2 were performed within 5 d of the final phase 1 and phase 2 training sessions, respectively, and to minimize any detraining effects, the time between transition between phases was less than 7 d.

Exercise interventions

Details of the exercise training regimens are published in detail (19). All exercise-training sessions lasted 45–60 min, including warm-up, training, and cooldown, and were conducted three times per week for a total of 12 wk. Participants were supervised by trained exercise physiologists, and all exercise sessions were supervised in the Duke University Medical Center and PBRC training facilities. Heart rates were continually monitored via Polar heart rate monitors (RS 400; Polar, Kampele, Finland) programmed with individualized heart rate ranges determined from the baseline CPET. After each session, heart rate data were analyzed for time spent in the prescribed training range and average heart rate achieved during each session. In addition, heart rate and exercise intensity were documented on paper every 5 min and adjusted if needed. Total aerobic exercise dose was estimated using published metabolic equations (21). Body weight was assessed weekly. Participants were required to complete at least 10 exercise sessions during the first 4 wk of AT or PRIME (phase 1) and at least 20 sessions during the after 8 wk of AT + RT (phase 2) (>80% adherence for both phases) to be included in the data analysis.

Participants assigned to AT during phase 1 performed whole-body aerobic exercise at >50% of heart rate reserve (HRR) on an Airdyne cycle ergometer (Nautilus, Inc., Vancouver, WA) using both arms and legs for 20 min (including a 5-min warm-up) and then walked on a treadmill for 25 min (including a 5-min cooldown). Participants exercised until the prescribed duration was achieved on each modality or until fatigue, at which point either the intensity of the exercise was reduced, or the exercise was paused until they recovered and were able to resume the training session. Participants that were initially unable to meet the training requirements were slowly progressed over subsequent sessions and encouraged to increase their workout intensity to the required range.

The phase 1 PRIME protocol was designed to focus on specific peripheral muscle groups without imposing a significant cardiorespiratory strain. Eight exercises were performed to target all major muscle groups and enable the routine to be completed within 60 min: warm-up, rest periods, stretching between exercises, and cooldown activities (see Table 1). Each exercise involved contractions with a moderate load, defined as 40%–50% of their maximal voluntary capacity, for a duration of up to 6 min. The lifting cadence was controlled by metronome at one contraction every 4 s, with at least 1 s of this time in an unloaded state. During each exercise, subjects were allowed to take rest breaks as needed, but it was prespecified that each break must be for a minimum of 30 s. Subject progression initially occurred by decreasing the number of required rest periods during each exercise. When the subject completed the whole duration of the exercise without rest, the load was increased by 10%. The volume for each exercise was calculated by multiplying the weight lifted by the number of repetitions completed and calculated as volume per exercise and total volume lifted per exercise session (sum of all exercises).

PRIME exercise protocol.

Phase 2 consisted of 8 wk of AT and RT as recommended by the ACSM and the U.S. Department of Health and Human Services (22). Each session included a 5-min warm-up, 30 min of AT, 20 min of traditional RT, and 5 min of cooldown. Participants started on an Airdyne cycle using both arms and legs for 20 min (including a 5-min warm-up) and then walked on a treadmill for 20 min (including a 5-min cooldown). To ensure an adequate progression during phase 2, participants were encouraged to work at an intensity corresponding to 60%–85% of HRR based on the baseline CPET test data during weeks 5–8 and 65%–85% of HRR during weeks 9–12. After AT, participants performed one set of 10–15 repetitions for eight exercises targeting all major muscle groups (19). The participants began with a load at which they were able to perform 10 repetitions using the correct technique and then increased the number of repetitions until they could perform 15 continuously. At that point, the weight was increased by 10%. Static stretches targeting the involved muscle groups (e.g., quadriceps stretch after leg press) were performed after each exercise was completed.

Testing protocols

Peak cardiorespiratory fitness was assessed on a treadmill using a Modified Naughton protocol. During the CPET, respiratory gases were collected to determine whether peak oxygen uptake (V˙O2peak) and heart rate were assessed using a standard 12-lead electrocardiogram. Blood pressure and rating of perceived exertion were obtained at the end of each minute throughout the test. Peak workload and time to exhaustion during the CPET were recorded as surrogate measure for changes in exercise tolerance (23).

The combined weight total from 1RM isotonic testing on the seated row, chest press, leg press, and the isometric handgrip test (strongest hand) was used as the measure of muscular strength. To achieve a standardized 1RM on each exercise and between visits, participants were allowed five attempts at different weights, with appropriate rest periods between each lift, and were guided by a qualified exercise physiologist (24).

Physical function was assessed using the Fullerton SFT. The SFT is a validated battery of six physical tasks of daily living and is used to assess strength, flexibility, and endurance to detect and predict future limitations in functional capacity (25,26). The test is designed to evaluate physical fitness domains, including upper-body strength (arm curl repetitions over 30 s), lower-body strength (chair sit–stand repetitions over 30 s), upper and lower body flexibility (back scratch and chair sit and reach), balance and coordination (8-foot up-and-go), and aerobic endurance (6-min walk). This test is simple to administer, time effective, and safe and has been validated through tests of over 7000 men and women between the ages of 60 and 94 yr (25).

Statistical analysis

This study was originally undertaken to derive effect sizes for a larger study. We aimed to provide ideal conditions and ideal compliance and not to generalize to the hypothetical results anticipated when expanded to a larger population (where a range of compliance could be anticipated). Thus, a per-protocol criterion was applied developing the analysis data set. Detailed design and statistical considerations have been published previously (19). The primary end points were changed in cardiorespiratory and muscular fitness (V˙O2peak, 1RM) and physical function (SFT scores). To address the main hypothesis, the change scores from baseline (TA0) to 12 wk (TA2) for the primary end points were analyzed. Under the per-protocol criterion, only data from the 76 participants who met the required number of exercise sessions and training guidelines and had complete data sets for all three primary outcomes were included in the final analysis. The data resulting from this design were analyzed by a repeated-measures mixed model, assessing the change in the two phases (0–4 and 5–12 wk), controlling for the baseline of the outcome under study. Each model first assessed a group–time interaction, and, if nonsignificant, a main effects only model (group–time) was assessed. Analysis of change in these periods allowed for easy interpretation. Analytically, the intercept effect was of interest, indicating if the average change, across group and time, was 0. Rejection of this hypothesis indicated that the intervention was associated with improvement—across group and time. The time effect, thus, tested if the change was different between the two periods, the arm effect measured if the change differed across the two periods, and the arm–time effect assessed if the arm effect differed between times. Chi-square analysis was used to detect differences in the distribution of individual training responses to each of the primary outcome variables with the mean response used at the cut point. Data are reported as both mean ± SD of the change scores of the observed group data and as the adjusted change scores. P < 0.05 (two-tailed) was used as the criterion to declare statistical significance.


Participant characteristics

Of the 107 randomized subjects (54 AT and 53 PRIME), 76 (32 DUKE and 44 PBRC) completed the 3 months of training, complied to the protocol and had 100% complete data sets for each of the three major outcome measures of cardiorespiratory and muscular fitness (V˙O2peak and 1RM) and physical function (SFT scores), and were included in the final per-protocol analysis (Fig. 1). Table 2 and Table S1 (see Table, Supplemental Digital Content 1, baseline physiological variables, present the baseline characteristics of our 76 completing study participants and their baseline physiological TA0 results. There were no differences in baseline characteristics or fitness and function variables between subjects that completed the study (n = 76) and those that did not (n = 31).

Baseline characteristics.

Overall, the participants were 70% female, 88% Caucasian, ranging from 70 to 91 yr old and presented with a body mass index ranging from 19.8 to 45.9 kg·m−2. All participants were on standard medical therapy as directed by their primary care physician: 65% used antihypertensive medications, 34% used lipid medications, and 18% used diabetic medications.

Training data

Table 3 shows details of the weekly exercise training loads for PRIME and AT for phase 1 and phase 2 (AT + RT) included in the final analysis. Adherence rates for phase 1 were 96.8% and 98.3% for PRIME and AT, respectively. For phase 2, these rates were 90.0% and 88.7%, respectively.

Exercise training data.

Because it is intermittent in nature and can be recorded as a volume of weight lifted, for comparison purposes, PRIME is quantified as RT in Table 3. It is impractical to compare the volumes of work performed during phase 1 of the protocol between groups; however, we compared relative central cardiovascular intensity of the workload via the time spent at or above 50% HRR between the groups. The PRIME group spent an average of 13.2 + 12.5 min per session in or above the 50% HRR target zone compared with 30.6 + 9.8 min for the AT group (67% less time, P < 0.01, Table 3). Individual subject data show that 72% of the PRIME subjects spent less than 20 min in the HRR target zone compared with only 11% of the AT subjects (P < 0.01, Fig. 2).

The average time spent in the target heart rate range during each exercise session for phase 1 (A) and phase 2 (B) of the intervention protocol. Data are presented as mean ± SD, and statistical significance is denoted as *P < 0.01 for PRIME vs AT treatment conditions.

During phase 2, depending on individual physiological responses and personal preferences, subjects were performing the same AT + RT protocol with various intensities. There were no significant differences in the average energy expenditure during AT (382.8 vs 375.9 MET·min·wk−1, P = 0.69), total weight lifted in RT (5687.6 vs 5945.6 kg·wk−1, P = 0.52), or time at or above target HRR per session (28.4 vs 26.7 min, P = 0.16) between the groups.

Primary outcomes

Figure 3 (left panels) shows the data for the major outcome variables adjusted for baseline. Cardiorespiratory and muscular fitness (V˙O2peak, 1RM) and physical function (SFT) scores all increased significantly after 4 wk (TA1) and 12 wk (TA2) of intervention for each treatment group (both, P < 0.05). However, participants randomized to the PRIME group demonstrated a significantly greater increase than the AT group in V˙O2peak (2.37 + 1.83 vs 1.50 + 1.82 mL·kg−1·min−1, P < 0.05), combined maximal voluntary contraction (48.52 + 27.03 vs 28.01 + 26.15 kg, P < 0.01), and SFT score (22.50 + 9.98 vs 18.66 + 9.60 percentile, P < 0.05) after 12 wk (TA2), respectively. In addition, participants randomized to the PRIME group had a greater individual chance of a larger-magnitude improvement across the trial (Fig. 3 right panels). Specifically, 58% of PRIME versus 34% of the AT participants demonstrated an improvement in V˙O2peak greater than the overall sample mean change at 12 wk of 1.93 mL·kg−1·min−1 (P < 0.05). The percentage of participants with improvements in overall strength and SFT above the sample mean was 60% and 63% of PRIME compared with 18% and 18% for AT participants (both <0.05).

Group mean data adjusted for baseline values at the initial testing visit before randomization (left column) and waterfall graphs of individual training response to PRIME and AT treatment (right column). Top panels (A and B) represent peak cardiorespiratory capacity (V˙O2 mL·kg−1·min−1); middle panels (C and D) represent the combined maximal voluntary contraction of respective strength assessments (kg); and bottom panels (E and F) represent the percentile ranking for the Senior Fitness Assessment (%). Data are presented as mean ± 95% CI, and statistical significance is denoted as *P < 0.05, †P < 0.01, for PRIME versus AT from group mean increase at 12 wk in comparison with baseline.


The primary finding from this prospective, randomized, clinical exercise trial in individuals over the age of 70 yr at risk of losing functional independence is that 4 wk of PRIME training compared with initial AT training, followed by 8 wk of ACSM/AHA recommended (AT + RT) training, results in greater increases in physical fitness and physical function measures. As hypothesized, both exercise interventions also significantly increased fitness and functional parameters after 12 wk of training. When the changes in physical fitness and function are examined on an individual level (Fig. 3), 58%–63% of those randomized to the PRIME intervention increased fitness/function above the mean increase value for the whole 76 subjects compared with 34% of those in the AT group.

Results from the literature differ in estimates of the rates of physical and functional decline with normal aging. For aerobic fitness in those 70 yr and older, studies suggest a 2.6- to 6.3-mL·kg−1·min−1 (∼1 to 2 METs) loss in aerobic capacity per decade of further life (18,27). Given that an increase of just 2 mL·kg−1·min−1 in V˙O2peak may provide up to a 30% reduction in relative risk morbidity, mortality, and loss of independence (10,12), the reversal of the decline observed in this study (2.4 and 1.5 mL·kg−1·min−1 gains in the PRIME and AT groups) is an important and significant indicator of improved cardiorespiratory fitness and health status. It is noteworthy that despite significantly less time spent in an HRR training range than the AT group who were doing moderate to vigorous aerobic activity throughout, a significantly greater improvement in cardiorespiratory fitness was achieved at the end of the trial for those who initially undertook PRIME training.

The largest difference in performance gains between the two interventions was in muscular strength. After 12 wk of training, the PRIME participants increased their combined 1RM by 110 kg—78% more than the AT participants (Fig. 3C). This was not totally unexpected given the greater volume of work and practice used in phase 1. Recent data suggest that muscular strength (upper, lower, and trunk), ranked in age- and sex-specific tertiles, has the largest independent association with functional disability. At a 5-yr follow-up in 3658 men and women, those in the highest strength tertile had 50% less risk of becoming functionally disabled than the lowest tertile (28). In the same study, aerobic capacity independently reduced risk by a further 10%. This is particularly significant for the current trial population, where an avoidance of crossing the threshold to functional dependence is a major clinical goal.

Current exercise guidelines for the elderly lack clarity with regard to specific minimal or optimal doses of training for functional health outcomes. There is a lack of specificity with respect to optimally addressing the needs of individuals most at risk for losing functional independence (17). Older individuals may be unable to perform whole-body aerobic exercise at a sufficient intensity to elicit central and local vascular and skeletal tissue adaptations. Similarly, current RT guidelines may improve strength in the elderly, but not be of sufficient frequency and duration to provide other beneficial aerobic peripheral tissue adaptations. In fact, the 2008 Physical Activity Guidelines Advisory Committee report indicated a need to determine whether more innovative strategies are needed to prevent or postpone functional decline in older adults (20).

This study provides important information and an alternative approach to exercise interventions for elderly subjects at risk for losing functional independence. By initially focusing on peripheral muscle tissue beds with low-mass–high-repetition training, participants seem to be able to tolerate a greater volume of work at each muscle group during each exercise modality than would be possible when performing whole-body exercise modalities. The manner by which PRIME triggers the whole-body changes in such a relatively short period is presently unknown. Data from single limb studies using a similar approach were associated with rapid improvements in localized strength gains and vasodilatory reserve in younger populations (29), older populations (30), and populations with health conditions (31), suggesting that greater peripheral remodeling may be involved.

These peripheral adaptations combined with the low heart rate responses make PRIME training a feasible and potentially important initial approach to exercise and rehabilitation for a variety of low-functioning and centrally cardiopulmonary compromised populations. It appears to serve as a primer to allow peripheral tissues to increase both aerobic and strength adaptations to exercise simultaneously and optimize whole-body responses to training that follow, leading to greater gains in cardiorespiratory, muscular fitness and physical function.

Study limitations

This study had a per-protocol design, and exit data were not collected on participants who dropped out of the study or were excluded due to nonadherence. It is possible that different types of people (e.g., responders vs nonresponders) could be nonadherent or more likely to drop out of the two interventions. Given that dropout rates between baseline testing and week 12 were similar between PRIME (15%) and AT (11%), we suspect that this influence would be distributed equally between the interventions. This does not preclude that the findings would be unchanged if missing data were included in the analysis.

We have only examined responses to supervised training; we do not know how the findings might have differed in a home-based or community-based setting. The PRIME regimen in particular may be difficult for individuals to perform without assistance while practicing proper technique. Also, it is unknown if the benefits obtained during the course of the 3-month training period can be maintained long term. The results of this study may, however, be of value to the growing number of exercise and fitness professionals offering high-quality programs in several community-based settings and have implications for the design of exercise training studies in the elderly.


In participants over the age of 70 yr at a risk of losing functional independence, 8 wk of a standard combined AT and RT program when preceded by 4 wk of PRIME training regimen resulted in greater increases in cardiorespiratory and muscular fitness and physical function than a standard program of AT. This approach may be of particular utility for individuals with low cardiorespiratory fitness and reduced physical function. Other potential settings where this approach may be of value are those with chronic disease conditions of low functional capacity, such as congestive heart failure, pulmonary diseases, posttreatment cancer, and sarcopenia of the elderly.

This work was supported by the National Institutes of Aging (grant no. 1RC1AG035822) and the Claude D. Pepper Older Americans Independence Centers at Duke University (grant no. P30 AG028716).

The authors thank the staff of the Duke University Center for Living, Pennington Biomedical Research Center, and the Department of Kinesiology at Louisiana State University.

All authors have no conflicts of interest to disclose. The results of the present study do not constitute endorsement by the ACSM.

The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.


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Supplemental Digital Content

© 2018 American College of Sports Medicine