The global number of people aged 80 years or over is projected to triple, from 143 million in 2019 to 426 million in 2050 (Nations, 2022). Similar projections are made for Europe (Eurostat, 2022) and Latin America and the Caribbean (OECD & The World Bank, 2020). In countries such as Chile, within the next 30 years, >30% of the older population (65+ years), will be 80 years or over (Aranco et al., 2018). Aging is associated with the loss of skeletal muscle mass and strength and a decline in physical performance, which decreases the ability to perform activities of daily living and lowers the quality of life. Therefore, it is important to develop effective strategies that support maintenance of skeletal muscle mass and strength throughout the lifespan, thereby preventing the development of sarcopenia and associated morbidity and functional decline within the older population (Xu et al., 2020).
It has been well established that resistance exercise training increases muscle mass, strength, and function in older adults (65–75 years; Churchward-Venne et al., 2015; Da Boit et al., 2017; Holwerda et al., 2018; Leenders et al., 2013; Marcos-Pardo et al., 2019; Phillips et al., 2015; Snijders et al., 2017; Turpela et al., 2017). By comparison, limited work has been performed in older adults at a more advanced age (>80 years; Bechshoft et al., 2017; Bruunsgaard et al., 2004; Fiatarone et al., 1990, 1994; Kalapotharakos et al., 2010; Karlsen et al., 2019; Raue et al., 2006, 2009; Serra-Rexach et al., 2011; Slivka et al., 2008; Williamson et al., 2010). Whereas previous work has demonstrated significant gains in muscle strength and functional mobility following high-intensity resistance exercise training in older men and women at ages beyond 80 years, most of these studies failed to detect measurable increases in skeletal muscle mass and fiber size (Fiatarone et al., 1990, 1994; Karlsen et al., 2019; Raue et al., 2009). It was suggested that at such an advanced-age (>80 years) older adults may experience a blunted muscle hypertrophic response to resistance exercise training (Raue et al., 2009). This proposed blunted skeletal muscle adaptive response to resistance exercise training may be attributed to age-related mitochondrial dysfunction (Hepple, 2016; Ubaida-Mohien et al., 2022), axonal degeneration and/or motor neuron loss and neuromuscular junction instability (Hepple & Rice, 2016), Type II muscle fiber-specific decline in satellite cell content (Verdijk et al., 2014), changes in circulating hormone concentrations (van den Beld et al., 2018), and chronic low-grade systemic inflammation (Draganidis et al., 2021). However, whether these observations are related to a more advanced age per se or whether these are associated with changes in lifestyle at a more advanced age remains unclear. We are skeptical with regard to the suggestion that the skeletal muscle adaptive response is attenuated in older adults above 80 years when compared to older adults 65–75 years (Cruz-Jentoft et al., 2014; Phillips, 2015; Tieland et al., 2012). Therefore, we aimed to test the hypothesis that the skeletal muscle adaptive response to prolonged resistance exercise training is reduced at a more advanced age.
In the present study, we compare the efficacy of whole-body resistance exercise training to increase muscle mass and strength and improve functional capacity in older adults 65–75 years compared with older adults above 85 years. Therefore, 17 healthy older adults 65–75 years and 12 healthy older adults above 85 years were enrolled in a 12-week resistance exercise training program. Before, during, and after the exercise training program muscle mass, strength, and functional capacity were assessed.
Methods
See Supplementary Material (available online) for full methods text.
Participants and Experimental Design
Twenty-nine healthy participants, 17 older adults 65–75 years (OLDER 65–75; n = 13/4 [female/male]; 68 ± 2 years; 26.9 ± 2.3 kg/m2) and 12 older adults above 85 years (OLDER 85+; n = 7/5 [female/male]; 87 ± 3 years; 26.0 ± 3.6 kg/m2) completed this prospective clinical trial (see Supplementary Figure S1 [available online]). The study was approved by the scientific ethical committee of Universidad de La Frontera, Temuco, Chile (registration record N°107_18, Folio N°094/18), was performed in accordance with the Declaration of Helsinki and was registered on clinicaltrials.gov as NCT04999501. All volunteers performed 12 weeks of supervised whole-body resistance exercise training (three times per week). Before, and after 6 and 12 weeks of training, a computed tomography scan of the upper leg and lumbar spine vertebra 3 (L3) region was performed to assess quadriceps and L3 muscle cross-sectional area (CSA). In addition, fasting blood samples were obtained to determine biochemical and inflammatory markers, and a whole-body dual-energy X-ray absorptiometry scan was performed to determine lean and fat mass. Maximal strength was determined by one-repetition maximum (1RM); physical performance by the timed up and go (TUG) test, and short physical performance battery (SPPB); and health-related quality of life by the 36-Item Short Form Survey, and Lawton and Brody Instrumental Activities of Daily Living Scale at the same time points.
Screening and Testing
Prior to the study, volunteer eligibility to participate was assessed in a single screening session. After explaining all procedures, written informed consent was obtained. The inclusion criteria were aged from 65–75 years or ≥ 85 years, 18.5 < body mass index <30 kg/m2, and community-dwelling. Exclusion criteria were performing regular resistance exercise training in the previous 6 months, cardiovascular diseases that are contradictory for physical activity, and all co-morbidities interacting with mobility and muscle metabolism of the body and that do not allow to (safely) perform the resistance exercise training program. Eligibility was screened using anthropometric measures; blood pressure; and questionnaires on general health, medical history, medication use, and sports activities. At the end of the screening session, a familiarization trial was performed for the strength assessment on the different exercise machines.
Exercise Intervention Program
Supervised whole-body resistance exercise training was performed three times per week during the 12-week exercise training intervention. Training consisted of a 5-min warm-up on a cycle ergometer and global upper limb movements (flexion–extension and abduction–adduction of the shoulder), followed by one warm-up and four regular sets on both the leg press and the leg extension machines (TuffStuff Fitness International). Upper body exercises (chest press, latissimus dorsi pulldown [lat pulldown], and horizontal row; Ffit Tech) were performed with two sets of each exercise. Each exercise session ended with 5 min of cooldown through global muscle stretching exercises. During the first 6 weeks of training, the workload was increased from 60% to 80% of 1RM (10 repetitions in each set). Thereafter, 1RM was reassessed to adjust workloads (60%–80%) over the next 6 weeks. Compliance for the per-protocol analyses was set at completing at least 80% of the training sessions (i.e., at least 29 of the 36 sessions).
Dietary Intake and Physical Activity Standardization
Participants were instructed to maintain their normal dietary and physical activity habits. Three-day dietary intake records and physical activity records were kept before and at the end (Week 11) of the intervention to corroborate no major changes in their diet or in habitual physical activity had taken place. Other than that, there was no dietary control around each individual exercise session or throughout the study.
Quadriceps and L3 Muscle Cross-Sectional Area
Anatomic CSA of the quadriceps muscle and L3 region was assessed by computed tomography scanning (Somatom Sensation 16, Siemens). All computed tomography analyses were performed by an investigator blinded to participant coding.
Body Composition
Whole-body and regional lean mass and whole-body fat mass were determined by dual-energy X-ray absorptiometry scanning (Lunar General Electric iDEXA, General Electric Medical Systems). In addition, weight, height, waist circumference, and leg volume were determined.
Strength Assessment
Maximum strength was assessed using 1RM strength tests. Maximum strength was first estimated using the multiple-repetition procedure during the familiarization trial. In a separate session, 1RM strength was subsequently determined for all lower and upper body exercises on the same equipment as used for training. In addition, maximal handgrip strength was obtained using a Jamar electronic handheld dynamometer (model Plus+, Patterson Medical).
Physical Performance and Quality of Life
Physical performance was assessed by performing the TUG and SPPB. Health-related quality of life was assessed by the 36-Item Short Form Survey questionnaire, and the Lawton and Brody Instrumental Activities of Daily Living Scale questionnaire was used to assess the ability to perform instrumental activities of daily living.
Blood Samples
Fasting blood samples were collected to determine serum glucose; triglycerides; total cholesterol; high-density lipoprotein cholesterol; low-density lipoprotein; ultrasensitive C-reactive protein; insulin; interleukin (IL)-4, IL-6, IL-10, IL-13, IL-15; and tumor necrosis factor-alpha (TNF-alpha) concentrations. The homeostasis model assessment was calculated to assess insulin sensitivity using the following formula: fasting insulin concentration, μU/ml × fasting glucose, mmol/L/22.5 (Acosta et al., 2002).
Statistics
Based on previous work (Fiatarone et al., 1994; Raue et al., 2009; Verdijk, Jonkers, et al., 2009), we expected the increase in quadriceps CSA to be 9% ± 5% in OLDER 65–75 participants versus only half of that increase or less (≤4.5% ± 5%) in OLDER 85+ participants. With α = .05, and power = 0.80, we needed n = 21 subjects per group. Taking 20% dropout into account, we needed a minimum of n = 27 per group and finally aimed to include 60 older females and males (30 participants in each group). Due to COVID-induced lockdowns and subsequent national and local restrictions, we were only able to include 29 participants for final analyses (see Supplementary Figure S1 [available online]). To further objectify our findings, we provide effect size estimates for all main outcomes. All data are expressed as mean ± standard deviation (SD), as well as percentage change (from baseline to posttraining) to compare both the absolute and the relative improvements between the groups. Baseline characteristics between groups were compared by means of an independent samples t test. Pre- versus postintervention data were analyzed using a repeated-measures analysis of variance (ANOVA) with time (T1 vs. T2 vs. T3) as the within-subject factor and group (OLDER 65–75 vs. OLDER 85+) as the between-subject factor. In the case of a significant interaction, separate analyses were performed to determine time effects within groups and independent t tests for group differences in the T1, T2, and T3 values. For the main parameters, partial eta squared was used to estimate effect sizes and represented as η2. All calculations were performed using SPSS (version 24.0).
Results
Participants’ Characteristics, Anthropometrics, Dietary Intake, and Physical Activity Levels
In total, 78 participants were screened, but only 31 participants underwent the initial evaluation (T1, before intervention), due to exclusion criteria as well as COVID-19 restrictions during the experimental phase of the study. After voluntary dropout of another n = 2, 29 participants were considered for the final analysis (Supplementary Figure S1 [available online]). At baseline, participants in the OLDER 85+ group were on average 19 years older than participants in the OLDER 65–75 group, with no further differences in height, weight, body mass index, blood pressure, and waist circumference (Table 1). Twelve weeks of resistance exercise training induced a small but significant decrease in waist circumference in both the OLDER 65–75 and OLDER 85+ groups (time: p = .041; η2 = .11; Table 2), with no differences between groups (Time × Group: p = .283). Body weight and body mass index did not change throughout the intervention period (Table 2). Dietary intake data are presented in Supplementary Table S1 (available online). No significant differences were observed in the macronutrient composition of the diet (all p > .05). Protein intake averaged 1.1 ± 0.4 and 1.2 ± 0.4 g·kg BW−1·day−1 in the OLDER 65–75 and OLDER 85+ participants, respectively. No differences were observed between groups, and no changes were observed over time for any of the dietary intake parameters. Similarly, no significant changes were observed after 12 weeks of resistance exercise training in the physical activity level (interaction effect p = .256). Average number of steps per day were 5,599 ± 3,562 and 2,059 ± 1,860 steps at baseline and 5,551 ± 2,925 and 2,865 ± 2,031 steps in Week 11 in OLDER 65–75 and OLDER 85+, respectively (group effect p = .004).
Participants’ Characteristics
| OLDER 65–75 (n = 17) | OLDER 85+ (n = 12) | p | |
|---|---|---|---|
| Age (years) | 68 ± 2 | 87 ± 3 | .000 |
| Height (m) | 1.60 ± 0.09 | 1.55 ± 0.07 | .087 |
| Weight (kg) | 69.3 ± 11.1 | 62.2 ± 9.1 | .081 |
| BMI (kg/m2) | 26.9 ± 2.3 | 26.0 ± 3.6 | .431 |
| SBP (mmHg) | 133 ± 13 | 132 ± 13 | .911 |
| DBP (mmHg) | 80 ± 8 | 75 ± 11 | .152 |
| HR (bpm) | 71 ± 12 | 75 ± 12 | .396 |
| Waist circumference (cm) | 93.3 ± 10.0 | 90.9 ± 10.7 | .539 |
Note. Data were analyzed using independent samples t tests. Data are mean ± SD. Bold values indicate p < .05. OLDER 65–75 = females and males aged 65–75 years; OLDER 85+ = females and males aged ≥85 years; BMI = body mass index; SBP = systolic blood pressure; DBP = diastolic blood pressure; HR = heart rate; bpm = beats per minute.
Anthropometry and Body Composition Parameters Before, During, and After 12-Week Resistance Exercise Training
| OLDER 65–75 (n = 17) | OLDER 85+ (n = 12) | Statistics (p) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Before | Week 6 | After | Before | Week 6 | After | Time | Time × Group | Group | |
| Weight (kg) | 69.3 ± 11.1 | 68.5 ± 11.2 | 68.7 ± 11.2 | 62.2 ± 9.1 | 61.7 ± 9.4 | 62.2 ± 9.7 | .109 | .519 | .097 |
| BMI (kg/m2) | 26.9 ± 2.3 | 26.6 ± 2.4 | 26.6 ± 2.4 | 26.0 ± 3.6 | 25.8 ± 3.6 | 26.0 ± 3.7 | .092 | .558 | .498 |
| Waist circumference (cm) | 93.3 ± 10.0 | 92.4 ± 10.0 | 92.3 ± 11.0 | 90.9 ± 10.7 | 88.4 ± 11.1 | 90.4 ± 9.8 | .041 | .283 | .475 |
| Leg volume (L) | 7.4 ± 1.2 | 7.3 ± 1.2 | 7.3 ± 1.2 | 6.6 ± 0.9 | 6.5 ± 0.8 | 6.7 ± 0.8 | .460 | .210 | .065 |
| Whole-body fat mass (kg) | 25.5 ± 5.5 | 25.1 ± 5.5 | 25.0 ± 5.4 | 21.1 ± 6.3 | 20.9 ± 6.0 | 21.4 ± 6.4 | .180 | .052 | .076 |
| Whole-body lean mass (kg) | 40.5 ± 8.0 | 40.9 ± 8.6 | 41.3 ± 8.7 | 37.7 ± 5.0 | 38.1 ± 5.4 | 38.3 ± 5.2 | .001 | .846 | .310 |
| Appendicular lean mass (kg)a | 16.7 ± 4.2 | 17.0 ± 4.2 | 17.0 ± 4.0 | 15.3 ± 2.2 | 15.6 ± 2.4 | 15.7 ± 2.4 | .048 | .889 | .319 |
| L3 muscle CSA (cm2)b | 129 ± 32 | 131 ± 32 | 131 ± 31 | 123 ± 23 | 125 ± 27 | 125 ± 27 | .155 | .968 | .611 |
| L3 skeletal muscle index (cm2/m2)b | 50.1 ± 8.7 | 50.7 ± 8.9 | 51.1 ± 8.4 | 51.3 ± 7.8 | 52.0 ± 9.1 | 52.2 ± 9.3 | .155 | .979 | .709 |
Note. Data were analyzed using repeated-measures ANOVA (Time × Group). Data are mean ± SD. Bold values indicate p < .05. ANOVA = analysis of variance; OLDER 65–75 = females and males aged 65–75 years; OLDER 85+ = females and males aged ≥85 years; BMI = body mass index; CSA = cross-sectional area; L3 = lumbar spine vertebra 3.
aDetermined with 11 participants in OLDER 85+ group. bDetermined with 16 participants in OLDER 65–75 group.
Muscle Mass and Body Composition
At baseline, mean quadriceps CSA was smaller in OLDER 85+ versus OLDER 65–75 participants (p = .034; Figure 1). Whole-body resistance exercise training increased quadriceps CSA after both 6 and 12 weeks (Figure 1a), from 46.5 ± 10.7 at baseline to 51.1 ± 12.1 cm2 after training in the OLDER 65–75 and from 38.9 ± 6.1 at baseline to 43.1 ± 8.0 cm2 after training in the OLDER 85+ (time effect: p < .001; η2 = .67) with no differences between groups (Time × Group: p = .70; η2 = .012). In accordance, the relative increase in quadriceps CSA was not different between OLDER 65–75 (10% ± 4%) and OLDER 85+ (11% ± 5%; p = .59; η2 = −.14; Figure 1b). Of note, all participants increased quadriceps CSA, with the increase ranging from 1% to 18% in OLDER 65–75 and from 6% to 21% in OLDER 85+. L3 muscle CSA as well as L3 skeletal muscle index at baseline did not differ between groups, and no changes were observed throughout the 12-week intervention period in either group (Table 2).
—Skeletal muscle mass assessed by (a) quadriceps muscle CSA before, during, and after 12-week resistance exercise training and (b) percentage change in quadriceps CSA following 12 weeks of training in OLDER 65–75 (65–75 years, n = 17) and OLDER 85+ (≥85 years, n = 11) groups. Data were analyzed using repeated-measures ANOVA (Time × Group) (a) and independent t tests (b), not observing interaction or differences between the groups, respectively. ANOVA = analysis of variance; CSA = cross-sectional area; OLDER 65–75 = females and males aged 65–75 years; OLDER 85+ = females and males aged ≥85 years.
Citation: International Journal of Sport Nutrition and Exercise Metabolism 34, 1; 10.1123/ijsnem.2023-0087
No differences were observed in body composition between groups at baseline. Twelve weeks of resistance exercise training resulted in a 2% ± 3% (range [−2, +8]) and 2% ± 3% (range [−3, +5]) increase in whole-body lean mass (time effect: p = .001; η2 = .22), and a 2% ± 5% and 2% ± 6% increase in appendicular lean mass (p = .048; η2 = .11) in the OLDER 65–75 and OLDER 85+ groups, respectively, with no differences in the response to exercise training between groups (Time × Group: all p > .80; all η2 ≤ .006; Table 2). No differences in leg volume and whole-body fat mass were observed between groups, and no changes were observed over time (all p > .05; Table 2).
Strength
At baseline, 1RM leg extension and 1RM leg press strength were lower in OLDER 85+ versus OLDER 65–75 adults (both p < .05; Figure 2 and Table 3, respectively). After 12 weeks of whole-body resistance exercise training, 1RM leg extension (Figure 2) increased from 53 ± 25 to 71 ± 31 kg (38% ± 20%) in the OLDER 65–75 and from 36 ± 13 to 52 ± 20 kg (46% ± 14%) in the OLDER 85+ (time effect: p < .001; η2 = .77). In line with the CSA data, all participants showed increased 1RM leg extension strength, ranging from 5% to 76% in OLDER 65–75 and from 26% to 70% in OLDER 85+. Similar improvements were observed for 1RM leg press, lat pull down, chest press, and horizontal row (time effect: all p < .001; η2 ≥ .57), and grip strength (time effect: p = .010; η2 = .16) in the OLDER 65–75 and OLDER 85+ groups (Table 3). For all strength outcomes, no differences in the response to resistance exercise training were observed between groups for both the absolute and the relative (i.e., percentage) improvements (Time × Group: all p > .26; all η2 ≤ .05; Table 3).
—Leg extension strength assessed by (a) 1RM before, during, and after 12-week resistance exercise training, and (b) percentage change in leg extension 1RM, and physical performance assessed by (c) TUG before, during, and after 12-week resistance exercise training, and (d) percentage change in TUG following 12-week training in OLDER 65–75 (65–75 years, n = 17) and OLDER 85+ (≥85 years, n = 12) groups. Data were analyzed using repeated-measures ANOVA (Time × Group) (a, c) and independent t tests (b, d), not observing interaction or differences between the groups, respectively. 1RM = one-repetition maximum; TUG = the timed up and go test; ANOVA = analysis of variance; OLDER 65–75 = females and males aged 65–75 years; OLDER 85+ = females and males aged ≥85 years.
Citation: International Journal of Sport Nutrition and Exercise Metabolism 34, 1; 10.1123/ijsnem.2023-0087
Strength Parameters, Physical Performance (SPPB), Health Status (SF-36 Survey), and IADL (Lawton and Brody Scale) Before, During, and After 12-Week Resistance Exercise Training
| OLDER 65–75 (n = 17) | OLDER 85+ (n = 12) | Statistics (p) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Before | Week 6 | After | Before | Week 6 | After | Time | Time × Group | Group | |
| Strength | |||||||||
| 1RM leg press (kg) | 89.5 ± 33.4 | 105.7 ± 39.9 | 135.4 ± 47.0 | 69.6 ± 15.5 | 83.5 ± 16.2 | 105.2 ± 22.9 | .000 | .257 | .054 |
| 1RM lat pull down (kg) | 61.4 ± 13.3 | 65.7 ± 11.3 | 72.3 ± 12.9 | 62.1 ± 15.3 | 68.5 ± 17.2 | 76.3 ± 23.6 | .000 | .553 | .660 |
| 1RM chest press (kg) | 63.1 ± 20.0 | 68.6 ± 22.0 | 73.5 ± 22.2 | 53.6 ± 18.3 | 60.2 ± 18.5 | 65.6 ± 22.5 | .000 | .677 | .276 |
| 1RM horizontal row (kg) | 35.6 ± 8.0 | 41.1 ± 10.8 | 49.5 ± 14.8 | 35.3 ± 10.0 | 40.4 ± 9.3 | 47.5 ± 12.3 | .000 | .794 | .784 |
| Grip strength (kg) | 30.3 ± 9.4 | 30.2 ± 8.7 | 31.5 ± 9.6 | 27.0 ± 7.8 | 27.8 ± 7.3 | 28.2 ± 7.6 | .010 | .387 | .355 |
| SPPB | |||||||||
| Balance test (points) | 3.9 ± 0.3 | 4.0 ± 0.0 | 3.9 ± 0.2 | 3.6 ± 0.7 | 3.8 ± 0.5 | 3.9 ± 0.3 | .179 | .377 | .005 |
| Walk time (s) | 3.7 ± 0.5 | 3.4 ± 0.5 | 3.3 ± 0.5 | 4.6 ± 1.4 | 4.4 ± 1.4 | 4.1 ± 0.8 | .017 | .907 | .003 |
| Walk speed (m/s) | 1.1 ± 0.2 | 1.2 ± 0.2 | 1.2 ± 0.2 | 0.9 ± 0.2 | 1.0 ± 0.3 | 1.0 ± 0.2 | .011 | .575 | .003 |
| Chair stand test (s) | 9.5 ± 2.3 | 8.4 ± 1.4 | 7.3 ± 1.8 | 12.7 ± 3.8 | 10.0 ± 3.7 | 8.8 ± 4.6 | .000 | .091 | .047 |
| Total (points) | 11.6 ± 0.6 | 12.0 ± 0.0 | 11.9 ± 0.2 | 10.1 ± 1.9 | 10.8 ± 1.2 | 11.3 ± 1.4 | .004 | .146 | .001 |
| SF-36 | |||||||||
| Physical Component Summary (%) | 81.7 ± 11.6 | 79.3 ± 14.4 | 83.4 ± 11.0 | 66.8 ± 16.7 | 68.4 ± 17.5 | 70.7 ± 23.0 | .463 | .780 | .015 |
| Mental Component Summary (%) | 80.9 ± 14.6 | 80.0 ± 18.6 | 82.2 ± 13.8 | 73.4 ± 17.0 | 78.8 ± 13.0 | 78.5 ± 21.5 | .476 | .501 | .456 |
| IADL (points) | 8.0 ± 0.0 | 8.0 ± 0.0 | 7.9 ± 0.3 | 6.7 ± 1.6 | 6.7 ± 1.7 | 6.7 ± 1.6 | .802 | .802 | .002 |
Note. Data were analyzed using repeated-measures ANOVA (Time × Group). Data are mean ± SD. Bold values indicate p < .05. ANOVA = analysis of variance; OLDER 65–75 = females and males aged 65–75 years; OLDER 85+ = females and males aged ≥85 years; 1RM = one-repetition maximum; SPPB = Short Physical Performance Battery, IADL = Instrumental Activities of Daily Living; SF-36 = 36-Item Short Form Survey.
Physical Performance, Quality of Life, and Instrumental Activities of Daily Living
At baseline, OLDER 65–75 presented better physical performance than OLDER 85+ on both the TUG (p = .002, Figure 2) and SPPB-total points (p = .022, Table 3). Twelve weeks of resistance exercise training led to an average 7.7% ± 10.4% (from 7.5 ± 1.1 to 6.8 ± 0.7 s) and 12.9% ± 10.8% (from 11.6 ± 3.4 to 10.0 ± 3.0 s) improvement in TUG in OLDER 65–75 and OLDER 85+, respectively (time effect: p < .001; η2 = .30), with no differences between groups (Time × Group: p = .17; η2 = .06). The reduction in time needed for the TUG ranged from −33% to + 14% in OLDER 65–75 and from −27% to + 10% in OLDER 85+. In accordance, performance on the SPPB (total points, as well as all subitems with the exception of the balance test) improved in both the OLDER 65–75 and OLDER 85+ individuals (time effect: all p < .05; η2 ≥ .14), with no differences between groups (Time × Group: all p > .09; η2 ≤ .09; Table 3).
The quality of life assessed through the general health survey (36-Item Short Form Survey) was different between groups in the physical component summary (p = .015; η2 = .20; Table 3). Likewise, instrumental activities of daily living measured through Lawton and Brody Scale were somewhat lower in OLDER 85+ versus OLDER 65–75 (p = .002; η2 = .31; Table 3). For both measures, no changes were observed following 12-week resistance exercise training in either group.
Biochemical and Inflammatory Markers
At baseline, cholesterol, low-density lipoprotein, and insulin concentrations were lower in OLDER 85+ versus OLDER 65–75 adults (all p < .05, Supplementary Table S2 [available online]). On the contrary, IL-4, IL-6, and TNF-alpha concentrations were higher in OLDER 85+ versus OLDER 65–75 adults (all p < .05, Supplementary Table S3 [available online]). After 12 weeks of whole-body resistance exercise training, IL-10 concentrations (Supplementary Table S3 [available online]) decreased from 9.2 ± 4.6 to 7.8 ± 4.3 pg/ml in the OLDER 65–75 and from 9.8 ± 4.6 to 8.5 ± 3.5 pg/ml in the OLDER 85+ (time effect: p = .012; η2 = .15), with no differences between groups (Time × Group: p = .96; η2 = .001). No changes over time were observed for all other plasma parameters, including fasting plasma glucose, insulin, and homeostasis model assessment (Supplementary Tables S2 and S3 [available online]).
Discussion
In the present study, we show that 12 weeks of progressive whole-body resistance exercise training effectively increases quadriceps CSA, whole-body and appendicular lean mass, and upper and lower body muscle strength, and improves functional performance on the TUG and SPPB in both 65–75 years and 85+ years older men and women. Importantly, no differences in the beneficial effects of prolonged exercise training were observed between the OLDER 65–75 and OLDER 85+ men and women.
Aging is associated with muscle mass and strength loss that will lead to deterioration in physical performance. Resistance exercise training can be applied effectively to increase muscle mass, strength, and physical performance in the older population. In agreement, we show an approximate 2% increase in whole-body lean mass, ∼10% increase in quadriceps CSA, ∼38% increase in 1RM leg extension strength, and ∼8% improvement in physical performance (TUG) in healthy older men and women aged between 65 and 75 years. These results are similar to previous works (Churchward-Venne et al., 2015; Leenders et al., 2013; Verdijk, Gleeson, et al., 2009; Verdijk, Jonkers, et al., 2009) and confirm that the progressive, high-intensity resistance exercise training regimen applied in the current study was effective in inducing both muscle structural and functional improvements in older adults.
Although the general benefits of resistance exercise training have been well established for the older population, it has previously been suggested that the extent of the adaptive response may decline with a further increase in age. Indeed, the studies from Raue et al. (2009) and Fiatarone et al. (1990, 1994) showed less hypertrophy in 85-year-old women when compared to younger women (Raue et al., 2009), or even the absence of significant muscle hypertrophy following training in men and women aged 90 years and beyond (Fiatarone et al., 1990, 1994). In the present study, we specifically set out to compare the skeletal muscle adaptive response to resistance exercise training between OLDER 65–75 and OLDER 85+ men and women. We observed substantial muscle hypertrophy following 12 weeks of resistance exercise training with a 10% and 11% increase in quadriceps muscle CSA in the OLDER 65–75 and OLDER 85+ adults, respectively (Figure 1). Accordingly, substantial increases in muscle strength (Figure 2; Table 3) and improvements in physical function (Figure 2; Table 3) were evident following the training program, with no differences between the age groups. These findings clearly show that such an advanced age per se does not limit the adaptive response to resistance exercise training.
The observed efficacy of prolonged resistance exercise training to strongly increase muscle mass and strength and improve functional capacity, independently of age, may be in contrast to some of the previous work (Fiatarone et al., 1990, 1994; Raue et al., 2009). This discrepancy may be, at least partly, attributed to the applied exercise program. In the present study, we implemented a relative high exercise volume, including four sets on leg press and leg extension machines, when compared to previous works from Fiatarone et al. (1990, 1994) and Raue et al. (2009). The total volume of work performed represents an important factor in determining the exercise response, and this may be even more important for the older population where the applied (absolute) exercise intensity is typically low. Specifically, recent insights clearly show that apart from greater exercise intensity, also greater exercise volume (i.e., three vs. one exercise set and 3 vs. 1–2 training days a week) leads to greater improvements in skeletal muscle mass and strength in the older population (Currier et al., 2023; Fragala et al., 2019; Marques et al., 2023; Mcleod et al., 2023). Furthermore, in the present study, we recruited community-dwelling older men and women, who were able to adhere and comply with our demanding exercise program. In contrast, in the studies by Fiatarone et al. (1990, 1994), frail, institutionalized older people were included. The ability to properly respond to the exercise training regimen may be attenuated and/or delayed in those that already suffer from specific disease and/or general frailty, rather than based on the advanced age per se (Fiatarone et al., 1990, 1994; Strasser et al., 2018).
Despite similar benefits of resistance exercise training in the OLDER 65–75 and OLDER 85+ participants, the OLDER 85+ participants showed lower muscle mass, strength, and physical performance when compared to their younger counterparts. Nonetheless, metabolic disturbances were not evident as the OLDER 85+ showed lower insulin and low-density lipoprotein cholesterol levels and a lower homeostasis model assessment index of insulin resistance (Supplementary Table S2 [available online]) compared to their younger controls. Interestingly, plasma IL-6 and TNF-alpha concentrations were higher in the OLDER 85+ when compared with the older adults. These observations may be indicative of a more pro-inflammatory state (Supplementary Table S3 [available online]). High levels of pro-inflammatory markers such as IL-6, TNF-alpha, and C-reactive protein have been linked to loss of muscle mass, strength, and physical performance (Aleman et al., 2011; Bautmans et al., 2011; Haren et al., 2010; Nelke et al., 2019; Pan et al., 2021). No resistance exercise training-induced changes were observed in these blood parameters. Despite the lesser muscle mass, strength, and function and the more pro-inflammatory state, the OLDER 85+ men and women showed a similar response to resistance exercise training with substantial increases in muscle mass, strength, and function that did not differ from the older adults. As such, high-intensity resistance exercise training represents an effective treatment regimen to optimize muscular fitness independent of age. These findings are in line with our previous work in which we argued that there are not any nonresponders to the benefits of resistance exercise training on lean body mass, fiber size, strength, or function in the older population. Obviously, the current data support the idea there is always some level of heterogeneity in the response to exercise training. Importantly, however, this is not dependent on age per se, and in line with our previous work, all participants show improvements on one or more of the outcome measures. In fact, for quadriceps CSA as well as 1RM strength, our findings indicated that all individual participants improved throughout the 12-week training program. Contrary to what has been pointed out by some authors (Raue et al., 2009), we strongly advocate that resistance exercise training should be promoted without restriction to support more active, healthy aging, including people over 85 years.
Due to population aging, more attention is being directed to the stimulation of a more active lifestyle for older adults (Izquierdo et al., 2020). At a more advanced age, people are generally recommended to partake in low-intensity physical activities (such as easy walking, swimming, or dancing). Without detracting from the benefits of these exercise modalities, for example, cardiovascular health and overall well-being, when the aim is to increase skeletal muscle mass and strength, resistance exercise training with moderate to high workload intensity (60%–80% 1RM) should be pursued. However, only few studies have assessed the impact of resistance exercise training in adults aged in excess of 80 years (Fiatarone et al., 1990, 1994; Raue et al., 2009; Serra-Rexach et al., 2011). This study is the first to compare the effects of 12 weeks of resistance exercise training among community-dwelling OLDER 65–75 and OLDER 85+. We extend on previous work (Fiatarone et al., 1990, 1994; Raue et al., 2009) by showing that the substantial benefits of such a resistance exercise training regimen in healthy, community-dwelling participants are not restricted by age limit. Given that a lower number of participants than originally anticipated were included in the final analyses, it could be speculated that the lack of differences observed may relate to a potential lack of statistical power. However, performing a post hoc power calculation revealed that the power to detect the preset difference in quadriceps CSA as our main outcome (detailed in sample size calculation) was only modestly reduced to 0.75 (i.e., power achieved in this study). Moreover, the estimates of effect size included for all main outcome parameters were remarkably high for the training effect, but low for all Time × Group interactions, indicating that the COVID-induced limitation in recruitment rate had no major impact on the outcomes. In fact, to statistically detect the actually observed differences for the change in quadriceps CSA (i.e., 10% ± 4% vs. 11% ± 5%, which in itself would not be clinically relevant), more than n = 300 participants would be needed. Taken together, the observed lack of differences between the two age groups was not due to sample size-induced lack of power but rather showcases that the response was truly very similar between the 65–75 years and 85+ years older participants.
In conclusion, prolonged resistance exercise training increases muscle mass, strength, and physical performance in the aging population, with no differences between OLDER 65–75 and OLDER 85+ adults. The skeletal muscle adaptive response to resistance exercise training is preserved even in male and female adults older than 85 years.
Acknowledgments
We greatly appreciate the assistance of the following colleagues in the execution of the experiment: Fernanda Durán-Vejar, Francisca Beltrán-Fuentes, and Aris Muñoz-Fernández (all part of physiotherapy graduation, Universidad de La Frontera). Furthermore, technical expertise from Andrew Holwerda, Nicolás Saavedra, Marcela Sandoval, Franco Ramirez, Natalia Celedón, Gerardo Pizarro, and Daniela Martínez. Authorship: Study design: Marzuca-Nassr, Verdijk, van Loon. Experiments’ organization and performance: Marzuca-Nassr, Alegría-Molina, SanMartín-Calísto, Artigas-Arias, Sapunar, Huard, Salazar. Data analysis: Marzuca-Nassr, Verdijk. Data interpretation: Marzuca-Nassr, Verdijk, and van Loon. Manuscript drafting: Marzuca-Nassr. Editing and revision of manuscript: Marzuca-Nassr, Alegría-Molina, Verdijk, van Loon. Approved of final version: All authors. Funding Source: This research was carried out using financial support from ANID—FONDECYT—Chile (Grant Number 11180949). Clinical Trial Registration: NCT04999501.
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