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Fat infiltration and muscle hydration improve after high-intensity resistance training in women with sarcopenia. A randomized clinical trial

Open AccessPublished:November 03, 2022DOI:https://doi.org/10.1016/j.maturitas.2022.09.001

      Highlights

      • High-intensity resistance training (HIRT) can lessen the symptoms of sarcopenia in women.
      • Magnetic resonance imaging biomarkers related to muscle improve after HIRT.
      • After HIRT, strength and functional performance improve in sarcopenic older women.
      • After HIRT, levels of infiltrated microscopic fat decrease in muscle.
      • After HIRT, water diffusion and total muscular volume improve.

      Abstract

      Background

      Resistance training is recommended for preventing sarcopenia, but the benefits for the quality and quantity of muscle mass are uncertain.

      Objective

      To assess the effects of high-intensity resistance training (HIRT) on clinical and magnetic resonance imaging (MRI) parameters in women with sarcopenia.

      Methods

      A researcher-blinded randomized clinical trial was conducted. Community-dwelling older women with sarcopenia were randomized to six months of HIRT or a control group (CG). Body composition was assessed with bioimpedance equipment, and participants underwent strength and functional performance tests (short physical performance battery [SPPB] and gait speed). MRI scans of the thigh were taken to quantify muscle mass and quality.

      Results

      Thirty-eight women completed the study (20 in the HIRT group). Sarcopenia remitted in 50 % of the HIRT group. HIRT elicited a significant group × time interaction effect for muscle mass (p = 0.027; Ƞ2 = 0.129), muscle mass index (p = 0.023; Ƞ2 = 0.135), fat mass (p = 0.048; Ƞ2 = 0.103) and all strength variables (p < 0.05; Ƞ2 > 0.120). Moreover, the HIRT group obtained higher scores on the SPPB (mean difference [MD] 1.2; p = 0.005) and the 5 times sit-to-stand test (MD = 0.7; p = 0.009). Regarding MRI parameters, infiltrated microscopic fat decreased significantly (HIRT: MD = −0.01; p < 0.05), while hydration (T2) decreased in the CG (MD = 3.6 ms; p = 0.053) at six months. There were significant between-group differences at six months for water diffusion (HIRT: 1.09 × 10−3 mm2/s vs CG: 1.26 × 10−3 mm2/s) and total muscular volume (HIRT: 832.4 L vs CG: 649.2 L).

      Conclusions

      HIRT led to the remission of sarcopenia in half of the older women, as seen in muscle mass, strength, and functional performance and MRI biomarkers, with significant increases in muscle quality.

      Registered in ClinicalTrials.gov

      NCT03834558.

      Keywords

      1. Introduction

      From 2015 to 2050, the proportion of people over 60 will double, and the percentage of dependent elders will quadruple [
      • W. World Health Organization
      Ageing and health.
      ]. One of the main consequences of the loss of function is the decline of the locomotor system and particularly the decrease in muscle mass, also called sarcopenia. The European Working Group on Sarcopenia in Older People (EWGSOP) published guidelines for sarcopenia in 2010 [
      • Cruz-Jentoft A.J.
      • Baeyens J.P.
      • Bauer J.M.
      • Boirie Y.
      • Cederholm T.
      • Landi F.
      • Martin F.C.
      • Michel J.P.
      • Rolland Y.
      • Schneider S.M.
      • Topinková E.
      • Vandewoude M.
      • Zamboni M.
      Sarcopenia: European consensus on definition and diagnosis.
      ]. The definition of sarcopenia has evolved and is currently proposed from a two-dimensional perspective, taking into account the loss of both muscle mass and muscle function [
      • Cruz-Jentoft A.J.
      • Bahat G.
      • Bauer J.
      • Boirie Y.
      • Bruyère O.
      • Cederholm T.
      • Cooper C.
      • Landi F.
      • Rolland Y.
      • Sayer A.A.
      • Schneider S.M.
      • Sieber C.C.
      • Topinkova E.
      • Vandewoude M.
      • Visser M.
      • Zamboni M.
      • Bautmans I.
      • Baeyens J.P.
      • Cesari M.
      • Cherubini A.
      • Kanis J.
      • Maggio M.
      • Martin F.
      • Michel J.P.
      • Pitkala K.
      • Reginster J.Y.
      • Rizzoli R.
      • Sánchez-Rodríguez D.
      • Schols J.
      Sarcopenia: Revised European consensus on definition and diagnosis.
      ]. Nevertheless, while it is important to preserve lean mass, muscle quality also plays an important role in muscle function and functional performance [
      • Correa-de-Araujo R.
      • Harris-Love M.O.
      • Miljkovic I.
      • Fragala M.S.
      • Anthony B.W.
      • Manini T.M.
      The need for standardized assessment of muscle quality in skeletal muscle function deficit and other aging-related muscle dysfunctions: a symposium report.
      ].
      International guidelines strongly recommend the prescription of resistance-based training to manage sarcopenia [
      • Cruz-Jentoft A.
      Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS).
      ], as it can be effective to improve muscle mass [
      • Peterson M.D.
      • Sen A.
      • Gordon P.M.
      Influence of resistance exercise on lean body mass in aging adults: a meta-analysis.
      ], muscle strength [
      • Peterson M.D.
      • Rhea M.R.
      • Sen A.
      • Gordon P.M.
      Resistance exercise for muscular strength in older adults: a meta-analysis.
      ], and physical performance [
      • Churchward-Venne T.A.
      • Tieland M.
      • Verdijk L.B.
      There are no nonresponders to resistance-type exercise training in older men and women.
      ], even in very old people [
      • Stewart V.H.
      • Saunders D.H.
      • Greig C.A.
      Responsiveness of muscle size and strength to physical training in very elderly people: a systematic review.
      ]. The intensity of a training program can be determined from the use of 1 repetition maximum (1RM) [
      • Lavin K.M.
      • Roberts B.M.
      • Fry C.S.
      • Moro T.
      • Rasmussen B.B.
      • Bamman M.M.
      The importance of resistance exercise training to combat neuromuscular aging.
      ]. Some analyses have classified high-intensity resistance training (HIRT) as a workout at >70 % 1 RM [
      • Lavin K.M.
      • Roberts B.M.
      • Fry C.S.
      • Moro T.
      • Rasmussen B.B.
      • Bamman M.M.
      The importance of resistance exercise training to combat neuromuscular aging.
      ]. Studies show that higher-intensity resistance training is better for improving muscle strength [
      • Schoenfeld B.J.
      • Grgic J.
      • Ogborn D.
      • Krieger J.W.
      Strength and hypertrophy adaptations between low- vs. high-load resistance training.
      ], but greater changes in lean body mass were found with higher volumes of work. Nevertheless, newer research suggests that muscle hypertrophy can be equally achieved with different training loads [
      • Schoenfeld B.J.
      • Grgic J.
      • Ogborn D.
      • Krieger J.W.
      Strength and hypertrophy adaptations between low- vs. high-load resistance training.
      ] and that working until muscle failure is the most important factor [
      • Schoenfeld B.J.
      • Grgic J.
      • Ogborn D.
      • Krieger J.W.
      Strength and hypertrophy adaptations between low- vs. high-load resistance training.
      ,
      • Steele J.
      • Fisher J.
      • Giessing J.
      • Gentil P.
      Clarity in reporting terminology and definitions of set endpoints in resistance training.
      ,
      • Morton R.W.
      • Sonne M.W.
      • Farias Zuniga A.
      • Mohammad I.Y.Z.
      • Jones A.
      • McGlory C.
      • Keir P.J.
      • Potvin J.R.
      • Phillips S.M.
      Muscle fibre activation is unaffected by load and repetition duration when resistance exercise is performed to task failure.
      ]. A recent systematic review showed that physical activity improves physical performance and strength in people with sarcopenia, but its effect is inconsistent for muscle mass. Nevertheless, authors highlight the need for more randomized controlled trials (RCTs) to evaluate the isolated effects of physical activity [
      • Escriche-Escuder A.
      • Fuentes-Abolafio I.J.
      • Roldán-Jiménez C.
      • Cuesta-Vargas A.I.
      Effects of exercise on muscle mass, strength, and physical performance in older adults with sarcopenia: a systematic review and meta-analysis according to the EWGSOP criteria.
      ].
      Diagnosis of sarcopenia is based on clinical criteria, but the certainty of these parameters increases with biological and imaging markers like magnetic resonance imaging (MRI), considered the gold standard. Although there is no protocol with specific MRI biomarkers to characterize patients with sarcopenia, Sanz-Requena et al. has recently proposed a series of MRI-derived imaging parameters [
      • Sanz-Requena R.
      • Martínez-Arnau F.M.
      • Pablos-Monzó A.
      • Flor-Rufino C.
      • Barrachina-Igual J.
      • García-Martí G.
      • Martí-Bonmatí L.
      • Pérez-Ros P.
      The role of imaging biomarkers in the assessment of sarcopenia.
      ].
      Both the lack of global consensus on the diagnostic criteria for sarcopenia and the methodological heterogeneity of exercise programs applied justify the need for RCTs with quantified programs [
      • Escriche-Escuder A.
      • Fuentes-Abolafio I.J.
      • Roldán-Jiménez C.
      • Cuesta-Vargas A.I.
      Effects of exercise on muscle mass, strength, and physical performance in older adults with sarcopenia: a systematic review and meta-analysis according to the EWGSOP criteria.
      ]. At the same time, it is essential to add imaging techniques that elucidate the effect of exercise on muscle quantity and quality, given the absence of longitudinal studies that use this tool in people with sarcopenia. This study aimed to assess the effects of HIRT on EWGSOP-defined sarcopenia, kinanthropometric variables, muscle function, functional performance, and imaging biomarkers.

      2. Material and methods

      2.1 Study design and participants

      We designed a single (researcher)-blinded RCT based on a six-month HIRT intervention in community-dwelling older women with sarcopenia. The study period was October 2018 to March 2020. It was approved by the Research Ethics Committee of the Universitat de València (H1488746567568), which operates in accordance with the principles of the Declaration of Helsinki. The trial was registered with the US National Institutes of Health (ClinicalTrials.gov, NCT03834558).
      Inclusion criteria were: women aged 70 or older and diagnosed with sarcopenia according to EWGSOP consensus criteria [
      • Cruz-Jentoft A.J.
      • Baeyens J.P.
      • Bauer J.M.
      • Boirie Y.
      • Cederholm T.
      • Landi F.
      • Martin F.C.
      • Michel J.P.
      • Rolland Y.
      • Schneider S.M.
      • Topinková E.
      • Vandewoude M.
      • Zamboni M.
      Sarcopenia: European consensus on definition and diagnosis.
      ], able to walk independently (with or without technical aids), residing in the community in the health areas under study, and signed informed consent. Exclusion criteria were: life expectancy of less than six months, living in an institution, severe auditory or visual impairment, medical contraindication to performing physical activity, or contraindication for the MRI study (especially carriers of non-compatible pacemakers, neurostimulators, cochlear implants, and intracranial aneurysm clamping), severe psychiatric illness or moderate-to-severe cognitive impairment; refusal to sign informed consent prior to participation.

      2.2 Sample size

      Estimation of sample size for this investigation was performed using handgrip strength as one of our primary outcome measures. Sample size was estimated combining the normative data and the genuine change in grip strength determined in previous works [
      • Massy-Westropp N.M.
      • Gill T.K.
      • Taylor A.W.
      • Bohannon R.W.
      • Hill C.L.
      Hand grip strength: age and gender stratified normative data in a population-based study.
      ]. These assumptions generated a desired sample size of at least 30 participants.
      Participants were recruited through social centers for older adults in the city of Valencia (Spain), primary health care centers in the Valencia University Clinical Hospital health department, and the Hospital QuironSalud of Valencia.
      We used the sarcopenia criteria established by the EWGSOP [
      • Cruz-Jentoft A.J.
      • Baeyens J.P.
      • Bauer J.M.
      • Boirie Y.
      • Cederholm T.
      • Landi F.
      • Martin F.C.
      • Michel J.P.
      • Rolland Y.
      • Schneider S.M.
      • Topinková E.
      • Vandewoude M.
      • Zamboni M.
      Sarcopenia: European consensus on definition and diagnosis.
      ] to diagnose sarcopenia. The presence of low muscle mass (skeletal muscle index [SMI] < 6.68 kg/m2) [
      • Masanés F.
      • Rojano i Luque X.
      • Salvà A.
      • Serra-Rexach J.A.
      • Artaza I.
      • Formiga F.
      • Cuesta F.
      • Soto A. López
      • Ruiz D.
      • Cruz-Jentoft A.J.
      Cut-off points for muscle mass — not grip strength or gait speed — determine variations in sarcopenia prevalence.
      ] and weakness (handgrip strength < 20 kg) and/or low functional performance (gait speed ≤ 0.8 m/s) [
      • Cruz-Jentoft A.J.
      • Baeyens J.P.
      • Bauer J.M.
      • Boirie Y.
      • Cederholm T.
      • Landi F.
      • Martin F.C.
      • Michel J.P.
      • Rolland Y.
      • Schneider S.M.
      • Topinková E.
      • Vandewoude M.
      • Zamboni M.
      Sarcopenia: European consensus on definition and diagnosis.
      ] is necessary to diagnose sarcopenia (Appendices). After clinically evaluating 220 patients, 51 remained eligible and were evenly allocated to the HIRT intervention or control group (CG) using computer-based randomization.

      2.3 Randomization

      The 51 participants were assigned an identification number and allocated using computer-based block randomization, through the computer tool XLstats (XL stats. New York: Addinsoft Inc.; 2017) (HIRT n = 27; CG n = 24). A block size of four was established to ensure an equal chance of allocation to each group; allocation ratio 1:1. To guarantee secrecy, the sequence was generated by a statistician and given to the project manager.

      2.4 Process

      The study took place in the physical performance laboratory of the University of Valencia Physiotherapy School. To obtain data for between- and within-group comparisons, members of the research team who were not involved in implementing the intervention performed two measurements, one week before implementing the program and one week after its completion.
      Variables collected were kinanthropometric measures, muscle function, physical performance, and imaging biomarkers. To characterize the sample, we assessed the presence of comorbidities, the level of physical activity, the independence in activities of daily living and nutritional status (Appendices).

      2.5 Variables

      2.5.1 Kinanthropometric variables

      Bioelectrical impedance analyses (BIA) were carried out with a BC-418 MA BIA device (Tanita 2016, America) to measure body weight, muscle mass and fat mass. Height was measured with a stadiometer, and body mass index (BMI) was calculated. Calf and thigh perimeters were measured with a metric tape. SMI was calculated as muscle mass/height (kg/m2) (Appendices).

      2.5.2 Muscular function

      Maximum isometric contractions (MIC) of the dominant leg were assessed using a hand-held dynamometer (model 01165, LaFayette, USA) [
      • Cruz-Jentoft A.J.
      • Bahat G.
      • Bauer J.
      • Boirie Y.
      • Bruyère O.
      • Cederholm T.
      • Cooper C.
      • Landi F.
      • Rolland Y.
      • Sayer A.A.
      • Schneider S.M.
      • Sieber C.C.
      • Topinkova E.
      • Vandewoude M.
      • Visser M.
      • Zamboni M.
      • Bautmans I.
      • Baeyens J.P.
      • Cesari M.
      • Cherubini A.
      • Kanis J.
      • Maggio M.
      • Martin F.
      • Michel J.P.
      • Pitkala K.
      • Reginster J.Y.
      • Rizzoli R.
      • Sánchez-Rodríguez D.
      • Schols J.
      Sarcopenia: Revised European consensus on definition and diagnosis.
      ]. We followed the protocol described by Francis et al. [
      • Sanz-Requena R.
      • Martínez-Arnau F.M.
      • Pablos-Monzó A.
      • Flor-Rufino C.
      • Barrachina-Igual J.
      • García-Martí G.
      • Martí-Bonmatí L.
      • Pérez-Ros P.
      The role of imaging biomarkers in the assessment of sarcopenia.
      ]. Participants performed three MICs (kg) of knee extensors for 3 s, with 2-min rest periods between them, and we recorded the best (MIC) and mean values (average-MIC) [
      • Sanz-Requena R.
      • Martínez-Arnau F.M.
      • Pablos-Monzó A.
      • Flor-Rufino C.
      • Barrachina-Igual J.
      • García-Martí G.
      • Martí-Bonmatí L.
      • Pérez-Ros P.
      The role of imaging biomarkers in the assessment of sarcopenia.
      ]. Leg extension and seated leg press gym machines (F&H Fitness Equipment, Spain) were used to assess maximum dynamic muscle strength on the knees. Given the characteristics of the sample, we decided to calculate the predicted maximum strength using a submaximal maneuver. The Jamar Hydraulic Hand Dynamometer 5030J1 (Loughborough, UK) was used to measure dominant handgrip. We recorded the maximum value out of three assessments (Appendices).

      2.5.3 Functional performance

      Gait speed and the short physical performance battery (SPPB) were evaluated (Appendices).

      2.5.4 Imaging biomarkers obtained from MRI sequences

      MRI studies were performed within a week from the clinical and functional assessments, in the Radiology Service of the Hospital Quironsalud of Valencia, using a 3 Tesla unit (Philips Achieva, Philips Healthcare, Best, the Netherlands). We followed the image analysis protocol which has been published recently [
      • Sanz-Requena R.
      • Martínez-Arnau F.M.
      • Pablos-Monzó A.
      • Flor-Rufino C.
      • Barrachina-Igual J.
      • García-Martí G.
      • Martí-Bonmatí L.
      • Pérez-Ros P.
      The role of imaging biomarkers in the assessment of sarcopenia.
      ]. The study focused on the mid-thigh, and the following imaging biomarkers were used: water apparent diffusion coefficient (ADC), water interstitial diffusion coefficient (D), tissue hydration as transversal relaxation time (T2), proton density fat fraction (PDFF), fat/muscle/bone volumes, and macroscopic fatty infiltration.

      2.6 High-intensity resistance training (HIRT)

      The HIRT intervention consisted of two weekly 65 min sessions for six months, with a minimum recovery time of 72 h. Finally, participants in the HIRT group took part in up to 39 sessions (due to the university's vacation period). Each session consisted of three parts, starting with a 10-minute warm up, including joint mobility and postural control exercises. This was followed by a 45-min HIRT circuit, with six exercises to strengthen different muscle groups (two on the upper extremities, two on the trunk and two on the lower extremities). The present study focused only on the two lower extremity exercises (leg press and knee extension). Participants did three series of 10–15 repetitions until momentary failure [
      • Schoenfeld B.J.
      • Grgic J.
      • Ogborn D.
      • Krieger J.W.
      Strength and hypertrophy adaptations between low- vs. high-load resistance training.
      ,
      • Steele J.
      • Fisher J.
      • Giessing J.
      • Gentil P.
      Clarity in reporting terminology and definitions of set endpoints in resistance training.
      ,
      • Morton R.W.
      • Sonne M.W.
      • Farias Zuniga A.
      • Mohammad I.Y.Z.
      • Jones A.
      • McGlory C.
      • Keir P.J.
      • Potvin J.R.
      • Phillips S.M.
      Muscle fibre activation is unaffected by load and repetition duration when resistance exercise is performed to task failure.
      ]. After a period of individualized progression in training, the load was set to at least 70 % of 1RM. Finally, during a 10-min cool down phase, participants did self-massage for myofascial release and stretching exercises (Appendices).
      Two senior researchers (a graduate in physical and sports educations and a physical therapist) supervised and managed the interventions, applying corrective measures when necessary to correct posture, breathing, and technique to ensure proper execution and avoid injuries. Attendance to the sessions was recorded daily, and adherence was categorized as high (>65 % of sessions), moderate (34–65 %), or low (<34 %).
      The CG did not receive any specific intervention for sarcopenia. Their participation in the trial was limited to telephone follow-ups to assess their general health status.

      2.7 Statistical analyses

      All analyses were performed using IBM SPSS Statistics v22.0 (SPSS Inc., Chicago, IL, USA) software for Windows. Descriptive statistics were conducted for all variables at baseline, with quantitative data presented as means and standard deviation (SD) and qualitative data as absolute and relative frequencies. Moreover, groups were compared at baseline using the student t-test for quantitative variables and contingency tables and the chi-squared test for qualitative variables and sarcopenia status. We report the p value of the asymptotic significance test.
      Quantitative variables were analyzed in a two-way mixed-effect (between-within) ANOVA, including 2 (HIRT and CG) × 2 (time: pre-test, post-test) to assess the group × time interaction with repeated measures on the last factor using 95 % confidence intervals (CIs). Statistical significance was set at p < 0.05 for all tests. Effect sizes (eta squared, ⴄ2) for ANOVA were also calculated, with thresholds of >0.01 considered small, > 0.059, considered moderate and >0.138 considered large (Appendices). Bonferroni adjustments and post-hoc pairwise comparison were used.

      3. Results

      Fifty-one older women with sarcopenia were randomized (HIRT n = 24; CG n = 27; mean age 79.8 years SD 7.4), and 38 (74.5 %) fully completed the postintervention assessment (HIRT n = 20; CG = 18; Fig. 1). Of the 51 randomized people, 30 accepted the MRI analysis at the beginning and the end of the study (HIRT n = 14; CG = 16). Eight participants dropped out (HIRT n = 3; CG n = 5) due to the COVID-19 pandemic (HIRT n = 3; CG n = 3), one died (CG n = 1), and one was excluded because of an error in the imaging process (CG n = 1), so 22 participants were finally analyzed by MRI after intervention (HIRT n = 11; CG n = 11). Characteristics of the sample are presented in Table 1. Adherence was high in 75 % of participants, moderate in 20 %, and low in 5 %. Three cases of muscle discomfort attributed to intervention were observed after the first two weeks of HIRT. In all cases, the training load was adapted in the following sessions, returning to normality.
      Fig. 1
      Fig. 1CONSORT diagram showing participant flow through the trial (clinical variables).
      Table 1Baseline participant characteristics.
      VariableTotal

      Mean (SD) (n = 38)
      HIRT

      Mean (SD) (n = 20)
      Control

      Mean (SD) (n = 18)
      p value
      Age (years)79.8 (7.4)79.9 (7.2)79.6 (7.7)0.91
      Height (m)1.5 (0.1)1.5 (0.1)1.5 (0.1)0.79
      Body weight (kg)61.5 (9.1)59.6 (9.6)63.6 (8.2)0.19
      BMI (kg/m2)26.9 (3.7)26.2 (4.2)27.7 (2.9)0.21
      Brachial perimeter (cm)26.9 (2.7)26.3 (2.6)27.5 (2.8)0.17
      Calf perimeter (cm)32.6 (2.4)32.3 (2.0)33.0 (2.9)0.40
      Thigh perimeter (cm)48.4 (4.5)47.2 (3.8)49.6 (5.1)0.098
      Charlson Index (points)5.2 (1.8)5.4 (2.1)5.1 (1.5)0.36
      Fat mass (kg)23.7 (6.3)22.5 (7.1)25.0 (5.2)0.23
      Muscle mass (kg)36.1 (3.7)35.2 (4.0)37.1 (3.0)0.11
      Skeletal muscle index (kg/cm2)5.7 (0.7)5.6 (0.8)5.9 (0.6)0.57
      Handgrip (kg)18.2 (3.8)17.8 (3.2)18.6 (4.4)0.51
      MIC of knee extension (kg)
      16 participants were registered in the HIRT group; 2 could not perform the test.
      16.5 (6.2)17.6 (6.7)15.2 (5.4)0.25
      Average-MIC of knee extension (kg)
      16 participants were registered in the HIRT group; 2 could not perform the test.
      14.9 (5.9)15.9 (6.5)13.6 (5.0)0.26
      1RM knee extension (kg)3.2 (3.4)3.7 (3.7)2.8 (3.2)0.42
      1RM leg press (kg)59.2 (19.3)58.6 (21.0)59.9 (17.9)0.84
      Gait speed (m/s)0.75 (0.21)0.79 (0.24)0.71 (0.16)0.23
      Short Physical Performance Battery
       Total (points)7.8 (2.5)7.9 (2.7)7.7 (2.3)0.83
       Balance (points)2.9 (1.2)2.7 (1.1)3.1 (1.2)0.36
       Walk (points)2.7 (0.9)2.9 (0.9)2.4 (0.8)0.16
       5 times sit-to-stand (points)2.3 (1.4)2.4 (1.5)2.22 (1.3)0.78
      Barthel Index (points)93.6 (8.0)93.5 (9.5)93.6 (6.1)0.57
      International Physical Activity Questionnaire-Elderly (metabolic equivalent of task)868.3 (731.9)882.1 (830.7)853 (628.0)0.97
      Mini Nutritional Assessment-Short Form (points)12.5 (2.0)11.9 (2.4)13.1 (1.3)0.057
      Average-MIC: average of maximum isometric contraction; HIRT: high-intensity resistance training; MIC: maximum isometric contraction; SD: standard deviation; 1RM: 1 repetition maximum.
      a 16 participants were registered in the HIRT group; 2 could not perform the test.

      3.1 Kinanthropometric variables

      A significant group×time interaction effect was observed for body composition variables: SMI, muscle mass and fat mass measured by BIA, with a moderate effect size. The HIRT also showed an increase in muscle mass (mean difference [MD] 1.1 kg; p < 0.05) and SMI (MD 0.4 kg/m2; p < 0.001) in within-group analyses (Table 2).
      Table 2Results of the intra-group (time) analysis and time × group (interaction) comparative analysis for the clinic variables.
      VariableBaseline

      Mean (SD)
      Postintervention

      Mean (SD)
      Within-group

      Mean difference (95 % CI)
      Time × group (between-groups)
      Fp value2
      SMI (kg/m2)Control (n = 18)5.85 (0.58)5.79 (0.76)−0.06 (−0.33, 0.22)5.6170.023
      p < 0.05.
      0.135
      HIRT (n = 20)5.63 (0.79)6.02 (0.68)0.39 (0.13, 0.65)
      p < 0.01.
      Muscle mass (kg)Control (n = 18)37.12 (2.97)36.43 (4.13)−0.69 (−1.82, 0.44)5.3310.027
      p < 0.05.
      0.129
      HIRT (n = 20)35.20 (4.04)36.30 (4.07)1.11 (0.02, 2.19)
      p < 0.05.
      Fat mass (kg)Control (n = 18)25.04 (5.20)25.89 (6.61)0.85 (−0.65, 2.35)4.1120.048
      p < 0.05.
      0.103
      HIRT (n = 20)22.53 (7.09)21.29 (6.40)−1.25 (−2.69, 0.20)
      Body weight (kg)Control (n = 18)63.55 (8.23)63.44 (9.07)−0.11 (−1.08, 0.86)0.0010.97<0.001
      HIRT (n = 20)59.63 (9.60)59.50 (9.74)−0.14 (−1.05, 0.78)
      BMI (kg/m2)Control (n = 18)27.69 (2.89)27.52 (3.32)−0.17 (−0.54, 0.20)<0.0010.99<0.001
      HIRT (n = 20)26.18 (4.24)26.02 (4.32)−0.16 (−0.51, 0.19)
      Handgrip (kg)Control (n = 18)18.64 (4.41)17.56 (5.61)−1.08 (−2.88, 0.71)5.2560.028
      p < 0.05.
      0.127
      HIRT (n = 20)17.80 (3.24)19.55 (3.98)1.75 (0.03, 3.48)
      p < 0.05.
      Maximum isometric contraction knee extension (kg)
      A total of 16 participants were allocated to the HIRT group; 2 participants could not perform the test.
      Control (n = 19)15.47 (5.49)17.19 (7.89)1.72 (−1.19, 4.63)4.4340.043
      p < 0.05.
      0.122
      HIRT (n = 15)17.79 (6.80)23.53 (7.43)5.74 (3.16, 8.32)
      p < 0.01.
      Average- maximum isometric contraction knee extension (kg)
      A total of 16 participants were allocated to the HIRT group; 2 participants could not perform the test.
      Control (n = 19)13.89 (5.10)15.80 (7.24)1.91 (−0.80, 4.61)5.2140.029
      p < 0.05.
      0.140
      HIRT (n = 15)16.15 (6.59)22.11 (7.31)5.96 (3.56, 8.36)
      p < 0.01.
      1 repetition maximum knee extension (kg)Control (n = 18)2.75 (3.17)2.59 (2.99)−0.16 (−2.03, 1.70)40.912<0.001
      p < 0.01.
      0.532
      HIRT (n = 20)3.68 (3.69)11.32 (6.52)7.65 (5.94, 9.35)
      p < 0.01.
      1 repetition maximum leg press (kg)Control (n = 18)59.87 (17.88)58.13 (21.22)−1.74 (−10.82, 7.34)17.301<0.001
      p < 0.01.
      0.325
      HIRT (n = 20)58.61 (21.02)82.54 (19.62)23.94 (15.32, 32.55)
      p < 0.01.
      Gait speed (m/s)Control (n = 18)0.71 (0.16)0.76 (0.24)0.04 (−0.03, 0.12)0.0300.8640.001
      HIRT (n = 20)0.79 (0.24)0.85 (0.22)0.05 (−0.02, 0.13)
      SPPB (points)TotalControl (n = 18)7.72 (2.32)8.17 (2.87)0.44 (−0.42:1.31)1.6550.2060.044
      HIRT (n = 20)7.57 (3.06)8.67 (3.51)1.20 (0.38, 2.02)
      p < 0.01.
      BalanceControl (n = 18)3.06 (1.21)3.17 (1.20)0.11 (−0.56, 0.78)0.4030.5290.011
      HIRT (n = 20)2.70 (1.13)3.10 (1.29)0.40 (−0.24, 1.04)
      WalkControl (n = 18)2.44 (0.78)2.5 (0.99)0.06 (−0.21, 0.21)0.2650.6100.007
      HIRT (n = 20)2.85 (0.93)3.00 (0.86)0.15 (−0.11, 0.41)
      5STSControl (n = 18)2.22 (1.26)2.44 (1.42)0.22 (−0.28, 0.72)1.5740.2180.042
      HIRT (n = 20)2.35 (1.46)3.00 (1.56)0.65 (0.17, 1.13)
      p < 0.01.
      BMI: body mass index; CI: confidence interval; HIRT: high-intensity resistance training; F: two-way ANOVA (repeated measures); SD: standard deviation; SMI: skeletal muscle index; SPPB: short physical performance battery; 5STS: five times sit-to-stand; ⴄ2 = eta squared (effect size); thresholds of ⴄ2 >0.01 considered small, >0.059 moderate, and > 0.138 large.
      low asterisk p < 0.05.
      low asterisklow asterisk p < 0.01.
      a A total of 16 participants were allocated to the HIRT group; 2 participants could not perform the test.

      3.2 Muscular function and physical performance variables

      There was a significant interaction effect in strength variables: handgrip, MIC and average-MIC for knee extension, and leg press and knee extension 1RM variables. The effect size was large for average-MIC, 1RM leg press and 1RM knee extension, and moderate for handgrip and MIC. We found significant statistical increases in the HIRT group for total SPPB (MD 1.2 points, 95 % CI 0.38, 2.02; t(37) = 2.97, p = 0.005, r = 0.44) as well as for the 5STS test (MD 0.7 points, 95 % CI 0.17, 1.13; t(37) = 2.77; p = 0.009; r = 0.41), both with moderate effect size (Table 2).

      3.3 Imaging biomarkers

      Results of the mixed ANOVA of MRI biomarkers are shown in Table 3. At study end, we found a significant decline in PDFF in the HIRT group (MD −0.01, 95 % CI −0.02, −0.002; t(21) = −2.5; p = 0.021; r = 0.48) with a moderate-to-large effect size, while the CG showed no change. We also observed a tendency (p = 0.053) towards a decrease in muscular hydration level of T2* in the CG at six months. We observed significant differences in post-hoc analysis of baseline ADC variables between groups (MD 1.1 × 10−3, p = 0.003). Furthermore, we obtained significant between-group differences in post-intervention tests for D (MD 1.1 × 10−3, p = 0.039) and for absolute muscular volume (MD 183.2 L p = 0.021) (Fig. 2). No significant effects were observed in the group × time interaction analysis for any MRI variables.
      Table 3Results of the intra-group (time) analysis and time × group (interaction) comparative analysis for the MRI variables.
      VariableBaseline

      Mean (SD)
      Postintervention

      Mean (SD)
      Within-group

      Mean difference (95 % CI)
      Time × group (between-groups)
      Fp value2
      Apparent diffusion coefficient (10−3 mm2/s)Control (n = 11)1.11 (0.05)1.04 (0.10)−7.17 × 10−5 (0.10 × 10−3, −3.79 × 10−6)1.3810.250.065
      HIRT (n = 11)0.99 (0.12)0.98 (0.11)−1.04 × 10−5 (−8.73 × 10−5, 6.65 × 10−5)
      Diffusion coefficient (10−3 mm2/s)Control (n = 11)1.16 (0.16)1.26 (0.22)0.10 × 10−3 (−1.08 × 10−5, 0.10 × 10−5)1.8220.190.083
      HIRT (n = 11)1.09 (0.09)1.09 (0.13)−8.71 × 10−7 (0.10 × 10−9, 0.10 × 10−7)
      T2* (relaxation time, ms)Control (n = 11)37.72 (3.19)34.13 (6.26)−3.59 (−7.17, −0.01)
      p < 0.05.
      2.2830.150.102
      HIRT (n = 11)37.29 (2.61)37.43 (2.04)0.14 (−3.50, 3.77)
      Absolute fat volume (L)Control (n = 11)994.07 (409.57)1063.74 (446.66)69.67 (−19.03, 158.4)1.1710.290.055
      HIRT (n = 11)1401.49 (532.58)1406.08 (625.32)4.59 (−84.1, 93.3)
      Proton density fat fraction (no units)Control (n = 11)0.20 (0.02)0.20 (0.02)0.10 × 10−3 (−0.01, 0.10 × 10−5)1.9180.180.088
      HIRT (n = 11)0.21 (0.02)0.20 (0.02)−0.01 (−0.10 × 10−3, −0.10 × 10−4)
      p < 0.05.
      Macroscopic fatty infiltration (no units)Control (n = 11)0.33 (0.11)0.32 (0.13)−0.02 (−0.08, 0.04)0.0190.890.001
      HIRT (n = 11)0.29 (0.09)0.27 (0.09)−0.01 (−0.07, 0.05)
      p < 0.01.
      Absolute muscle volume (L)Control (n = 11)657.00 (278.90)649.18 (179.63)−7.82 (−90.76, 75.12)0.0110.920.001
      HIRT (n = 11)845.91 (201.49)832.36 (164.40)−13.55 (−92.46, 65.37)
      Muscle/fat ratio (no units)Control (n = 11)0.75 (0.32)0.74 (0.39)−0.01 (−0.09, 0.08)0.2460.630.012
      HIRT (n = 11)0.67 (0.27)0.69 (0.31)0.02 (−0.06, 0.10)
      Muscle/bone ratio (no units)Control (n = 11)12.99 (3.49)13.08 (3.36)0.08 (−1.42, 1.59)0.3590.560.018
      HIRT (n = 11)13.64 (3.85)14.28 (4.10)0.64 (−0.73, 2.01)
      CI: confident interval; HIRT: high-intensity resistance training; F: two-way ANOVA (repeated measures); SD: standard deviation; ⴄ2 = eta squared (effect size); thresholds of ⴄ2 >0.01 considered small, >0.059 moderate, and > 0.138 large.
      low asterisk p < 0.05.
      low asterisklow asterisk p < 0.01.
      Fig. 2
      Fig. 2Results of mixed ANOVA (pre-post differences within-group and between-group differences) for proton density fat fraction (PDFF, A), relaxation time (T2*, B), apparent diffusion coefficient (ADC, C) and diffusion (D) variables (D). Values expressed as mean and SD. Statistical significance was set at *p < 0.05 and **p < 0.01.

      3.4 Improvement of sarcopenia status

      At the beginning of the study, 100 % of the sample (HIRT n = 20; CG n = 18) presented sarcopenia. After six months of HIRT, 50 % (n = 10) of the intervention group had experienced remission of their sarcopenia, while severity decreased in the remaining 45 % (n = 9). In the CG, 27.8 % (n = 5) of the participants had no sarcopenia at six-month follow-up, and a similar proportion had severe sarcopenia (n = 6). There were no significant differences between groups in sarcopenia status (Ƞ2 = 1.96; p = 0.162) or sarcopenia severity (Ƞ2 = 0.33; p = 0.564) postintervention.

      4. Discussion

      Diverse studies have analyzed the effects of resistance training programs in older people with sarcopenia [
      • Chen H.T.
      • Wu H.J.
      • Chen Y.J.
      • Ho S.Y.
      • Chung Y.C.
      Effects of 8-week kettlebell training on body composition, muscle strength, pulmonary function, and chronic low-grade inflammation in elderly women with sarcopenia.
      ,
      • Cebrià i Iranzo M.
      • Balasch-Bernat M.
      • Tortosa-Chuliá M.
      • Balasch-Parisi S.
      Effects of resistance training of peripheral muscles versus respiratory muscles in older adults with sarcopenia who are institutionalized: a randomized controlled trial.
      ,
      • Hassan B.H.
      • Hewitt J.
      • Keogh J.W.L.
      • Bermeo S.
      • Duque G.
      • Henwood T.R.
      Impact of resistance training on sarcopenia in nursing care facilities: a pilot study.
      ], but ours is the first to study the influence of HIRT on MRI biomarkers in this population. Six months of HIRT led to an increase in muscular mass, a decrease in body fat mass assessed by BIA, and enhanced muscular strength and performance in the upper and lower limbs. Moreover, at within-group level, we observed improvements in muscular hydration and microscopic fat at midthigh in MRI analysis.
      Of the women receiving HIRT, 50 % experienced remission of their sarcopenia, while its severity diminished in almost all of the rest. These results are better than those achieved using lower-intensity resistance training programs of a similar duration [
      • Cebrià i Iranzo M.
      • Balasch-Bernat M.
      • Tortosa-Chuliá M.
      • Balasch-Parisi S.
      Effects of resistance training of peripheral muscles versus respiratory muscles in older adults with sarcopenia who are institutionalized: a randomized controlled trial.
      ,
      • Hassan B.H.
      • Hewitt J.
      • Keogh J.W.L.
      • Bermeo S.
      • Duque G.
      • Henwood T.R.
      Impact of resistance training on sarcopenia in nursing care facilities: a pilot study.
      ]. In fact, Hassan et al. [
      • Hassan B.H.
      • Hewitt J.
      • Keogh J.W.L.
      • Bermeo S.
      • Duque G.
      • Henwood T.R.
      Impact of resistance training on sarcopenia in nursing care facilities: a pilot study.
      ] reported an increase in the prevalence of sarcopenia in institutionalized old people after resistance training, generating more dependence after the intervention.
      Regarding body composition variables, we reported changes in muscle mass and fat mass of greater magnitude than in previous studies of both high [
      • Chen H.T.
      • Wu H.J.
      • Chen Y.J.
      • Ho S.Y.
      • Chung Y.C.
      Effects of 8-week kettlebell training on body composition, muscle strength, pulmonary function, and chronic low-grade inflammation in elderly women with sarcopenia.
      ] and moderate intensity [
      • Cebrià i Iranzo M.
      • Balasch-Bernat M.
      • Tortosa-Chuliá M.
      • Balasch-Parisi S.
      Effects of resistance training of peripheral muscles versus respiratory muscles in older adults with sarcopenia who are institutionalized: a randomized controlled trial.
      ,
      • Hassan B.H.
      • Hewitt J.
      • Keogh J.W.L.
      • Bermeo S.
      • Duque G.
      • Henwood T.R.
      Impact of resistance training on sarcopenia in nursing care facilities: a pilot study.
      ].
      Our results show an improvement in all strength variables after HIRT, compared to no change in the CG. Strength increased similar to other studies [
      • Chen H.T.
      • Wu H.J.
      • Chen Y.J.
      • Ho S.Y.
      • Chung Y.C.
      Effects of 8-week kettlebell training on body composition, muscle strength, pulmonary function, and chronic low-grade inflammation in elderly women with sarcopenia.
      ,
      • Cebrià i Iranzo M.
      • Balasch-Bernat M.
      • Tortosa-Chuliá M.
      • Balasch-Parisi S.
      Effects of resistance training of peripheral muscles versus respiratory muscles in older adults with sarcopenia who are institutionalized: a randomized controlled trial.
      ,
      • Hassan B.H.
      • Hewitt J.
      • Keogh J.W.L.
      • Bermeo S.
      • Duque G.
      • Henwood T.R.
      Impact of resistance training on sarcopenia in nursing care facilities: a pilot study.
      ,
      • Seo M.W.
      • Jung S.W.
      • Kim S.W.
      • Lee J.M.
      • Jung H.C.
      • Song J.K.
      Effects of 16 weeks of resistance training on muscle quality and muscle growth factors in older adult women with sarcopenia: a randomized controlled trial.
      ] in terms of both leg and hand isometrics and isotonics, reflecting the balance between intensity and duration of the intervention [
      • Escriche-Escuder A.
      • Fuentes-Abolafio I.J.
      • Roldán-Jiménez C.
      • Cuesta-Vargas A.I.
      Effects of exercise on muscle mass, strength, and physical performance in older adults with sarcopenia: a systematic review and meta-analysis according to the EWGSOP criteria.
      ]. We reported greater 1RM values, so HIRT produces improvements in neural factors implicated in force production [
      • Peterson M.D.
      • Rhea M.R.
      • Sen A.
      • Gordon P.M.
      Resistance exercise for muscular strength in older adults: a meta-analysis.
      ], which results in significantly increased physical ability (SPPB and 5STS) [
      • Escriche-Escuder A.
      • Fuentes-Abolafio I.J.
      • Roldán-Jiménez C.
      • Cuesta-Vargas A.I.
      Effects of exercise on muscle mass, strength, and physical performance in older adults with sarcopenia: a systematic review and meta-analysis according to the EWGSOP criteria.
      ], which is consistent with other physical activity interventions in older people [
      • Cook S.B.
      • LaRoche D.P.
      • Villa M.R.
      • Barile H.
      • Manini T.M.
      Blood flow restricted resistance training in older adults at risk of mobility limitations.
      ] and people with sarcopenia [
      • De Liao C.
      • Tsauo J.Y.
      • Huang S.W.
      • Ku J.W.
      • Hsiao D.J.
      • Liou T.H.
      Effects of elastic band exercise on lean mass and physical capacity in older women with sarcopenic obesity: a randomized controlled trial.
      ,
      • del Campo J.M.
      • Macías M.H.
      • Monroy R.
      Effect of a resistance training program on sarcopenia and functionality of the older adults living in a nursing home.
      ]. Although the change reported in gait speed was not significant, an increase of 0.06 m/s could be considered a small but clinically significant change [
      • Beaudart C.
      • Rolland Y.
      • Cruz-Jentoft A.J.
      • Bauer J.M.
      • Sieber C.
      • Cooper C.
      • Al-Daghri N.
      • Araujo de Carvalho I.
      • Bautmans I.
      • Bernabei R.
      • Bruyère O.
      • Cesari M.
      • Cherubini A.
      • Dawson-Hughes B.
      • Kanis J.A.
      • Kaufman J.M.
      • Landi F.
      • Maggi S.
      • McCloskey E.
      • Petermans J.
      • Rodriguez Mañas L.
      • Reginster J.Y.
      • Roller-Wirnsberger R.
      • Schaap L.A.
      • Uebelhart D.
      • Rizzoli R.
      • Fielding R.A.
      Assessment of muscle function and physical performance in daily clinical practice: a position paper endorsed by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).
      ]. Achieving more pronounced improvement could require specific exercises that focus on walking ability [
      • Escriche-Escuder A.
      • Fuentes-Abolafio I.J.
      • Roldán-Jiménez C.
      • Cuesta-Vargas A.I.
      Effects of exercise on muscle mass, strength, and physical performance in older adults with sarcopenia: a systematic review and meta-analysis according to the EWGSOP criteria.
      ] or perhaps other kinds of tests that assess walking ability at longer distances [
      • Jeon Y.
      • Shin M.
      • Kim C.
      • Lee B.-J.
      • Kim S.
      • Chae D.
      • Park J.-H.
      • So Y.
      • Park H.
      • Lee C.
      • Kim B.
      • Chang J.
      • Shin Y.
      • Kim I.
      Effect of squat exercises on lung function in elderly women with sarcopenia.
      ].
      The effects of HIRT on clinical variables were confirmed by MRI parameters. The most common parameter to assess the efficacy of an intervention is muscular volume, although its responsiveness to change depends on exercise type and the specific analysis of muscular volume. In our study, both groups reported a decrease in total muscular volume and an increase in total fat volume, which was more notable in CG. These results can be explained by the behavior of ratio parameters. The HIRT group showed an increase in the muscle/fat ratio, indicative of less loss of muscle than of fat, as opposed to CG. Considering the constant nature of bone volume [
      • Seo M.W.
      • Jung S.W.
      • Kim S.W.
      • Lee J.M.
      • Jung H.C.
      • Song J.K.
      Effects of 16 weeks of resistance training on muscle quality and muscle growth factors in older adult women with sarcopenia: a randomized controlled trial.
      ], the improvement in muscle is corroborated in the HIRT group by an increase in the muscle/bone ratio. Therefore, although there was an apparent decrease in total muscle volume, which could be attributable to the loss of BMI, the ratios are positive with respect to fat and bone, a finding that is consistent with Grimm et al.'s study in young people [
      • Grimm A.
      • Nickel M.D.
      • Chaudry O.
      • Uder M.
      • Jakob F.
      • Kemmler W.
      • Quick H.H.
      • Engelke K.
      Feasibility of Dixon magnetic resonance imaging to quantify effects of physical training on muscle composition—a pilot study in young and healthy men.
      ].
      Physical exercise tends to increase the cross-sectional area of the thigh or quadriceps heterogeneously [
      • Escriche-Escuder A.
      • Fuentes-Abolafio I.J.
      • Roldán-Jiménez C.
      • Cuesta-Vargas A.I.
      Effects of exercise on muscle mass, strength, and physical performance in older adults with sarcopenia: a systematic review and meta-analysis according to the EWGSOP criteria.
      ,
      • Seo M.W.
      • Jung S.W.
      • Kim S.W.
      • Lee J.M.
      • Jung H.C.
      • Song J.K.
      Effects of 16 weeks of resistance training on muscle quality and muscle growth factors in older adult women with sarcopenia: a randomized controlled trial.
      ], due to the type of exercise and methodological differences in the analysis of inter- and intramuscular fat mass, making it necessary to assess muscle quality in older adults with sarcopenia [
      • Correa-de-Araujo R.
      • Harris-Love M.O.
      • Miljkovic I.
      • Fragala M.S.
      • Anthony B.W.
      • Manini T.M.
      The need for standardized assessment of muscle quality in skeletal muscle function deficit and other aging-related muscle dysfunctions: a symposium report.
      ].
      Fat mass infiltration and muscular hydration were among the muscle quality parameters analyzed. Previous studies have reported a positive relationship between age and muscle fat infiltration [
      • Marcus R.L.
      • Addison O.
      • Kidde J.P.
      • Dibble L.E.
      • Lastayo P.C.
      Skeletal muscle fat infiltration: impact of age, inactivity, and exercise.
      ]. These fat deposits in the skeletal muscle affect neuromuscular activation and contribute to sarcopenia. We evaluated microscopic fat infiltration using the PDFF variable. Participants receiving HIRT showed a significant decrease in PDFF, in line with previous studies [
      • Ramírez-Vélez R.
      • Ezzatvar Y.
      • Izquierdo M.
      • García-Hermoso A.
      Effect of exercise on myosteatosis in adults: a systematic review and meta-analysis.
      ], which may contribute to improving or maintaining independence in older people.
      Regarding muscular hydration, we studied T2*, ADC and D parameters, which refer to the volume of muscle hydration and the microscopic mobility capacity of intratissue water, respectively. At six months, D values increased in the CG, which could be related with less movements of intratissue water due to the disestablishment (breakdown) of the muscle fibers and the presence of greater fat infiltration [
      • Yamada Y.
      Muscle mass, quality, and composition changes during atrophy and sarcopenia.
      ]. The HIRT group showed no changes in D. On the other hand, we observed a reduction of T2* in the CG at study end, an effect that may be associated with the presence of a greater extracellular space in atrophied muscles [
      • Yamada Y.
      Muscle mass, quality, and composition changes during atrophy and sarcopenia.
      ] and a greater presence of fat at intra and extra muscular level [
      • Sanz-Requena R.
      • Martínez-Arnau F.M.
      • Pablos-Monzó A.
      • Flor-Rufino C.
      • Barrachina-Igual J.
      • García-Martí G.
      • Martí-Bonmatí L.
      • Pérez-Ros P.
      The role of imaging biomarkers in the assessment of sarcopenia.
      ], related to muscular deterioration processes. In the CG, this was accompanied by lower lean mass in the different variables analyzed. Another hypothesis would indicate that the age-related decrease in T2* could be associated with an increase in extracellular water/total water rate [
      • Yamada Y.
      Muscle mass, quality, and composition changes during atrophy and sarcopenia.
      ], since the intracellular water value, which reflects muscle cell mass, significantly decreases with age, while extracellular water remains constant [
      • Yamada Y.
      Muscle mass, quality, and composition changes during atrophy and sarcopenia.
      ]. Both of these theories would reinforce our results, where the CG presented lower T2* values and higher levels of fat mass after six months, and they are concordant with the hypothesis postulated by Sanz-Requena et al., who speculated that people with lower fat mass show higher values of T2* and ADC because metabolic muscle activity is more preserved and muscle quality is higher [
      • Sanz-Requena R.
      • Martínez-Arnau F.M.
      • Pablos-Monzó A.
      • Flor-Rufino C.
      • Barrachina-Igual J.
      • García-Martí G.
      • Martí-Bonmatí L.
      • Pérez-Ros P.
      The role of imaging biomarkers in the assessment of sarcopenia.
      ]. All this would relate to a worse hydration level, a greater fat infiltrate, and lower metabolic activity at the muscle level, worsening the muscle function. However, more longitudinal studies are needed to analyze changes in muscle quality variables following a physical activity intervention in older people.
      Our study has some limitations. The data are limited to community-dwelling older women with sarcopenia. Secondly, there were 13 dropouts who were excluded from the analysis, with no intention-to-treat analysis to determine the effects. The lower number of participants in the MRI analysis compared to the clinical analysis was due to the restrictive measures imposed by the government during the first lockdown of the COVID-19 pandemic, which also meant that there was no long-term follow-up to analyze the maintenance of the effects obtained after the intervention.
      Six months of high-intensity resistance training led to remission of sarcopenia in half of the women who received the intervention. Body composition and muscular function improved, while imaging biomarkers corroborated the clinical outcomes and provided information on muscle quality, showing preserved levels of muscular hydration and a decrease of microscopic fat mass after the intervention.

      Contributors

      Cristina Flor-Rufino acquired the data, analyzed and interpreted the data and drafted the manuscript.
      Joaquin Barrachina-Igual acquired the data, analyzed and interpreted the data and revised the manuscript for key intellectual content.
      Pilar Pérez-Ros conceived and designed the study, analyzed and interpreted the data and drafted the manuscript.
      Ana Pablos-Monzo conceived and designed the study, analyzed and interpreted the data and drafted the manuscript and revised the manuscript for key intellectual content.
      Roberto Sanz-Requena conceived and designed the study, analyzed MRI data and revised the manuscript for key intellectual content.
      Francisco M. Martínez-Arnau conceived and designed the study, analyzed and interpreted the data, drafted the manuscript and supervised the study.

      Funding

      This work was supported by Universitat de València [grant number UV-19-INV_AE19] and Conselleria de Innovación, Universidades, Ciencia y Sociedad digital, Valencia, Spain [grant number GV/2020/071]. The sponsor had no role in the design, methods, subject recruitment, data collections, analysis and preparation of paper.

      Ethical approval

      This study was approved by the Research Ethics Committee of the Universitat de València (H1488746567568), which operates in accordance with the principles of the Declaration of Helsinki. All participants signed the informed consent for participation in the study.

      Provenance and peer review

      This article was not commissioned and was externally peer reviewed.

      Research data (data sharing and collaboration)

      There are no linked research data sets for this paper. Data will be made available on request.

      Declaration of competing interest

      The authors declare that they have no competing interest.

      Acknowledgements

      The authors thank all participants, Faculty of Physiotherapy of Universitat de València, University of Valencia (Grant UV-19-INV_AE19) and Conselleria de Innovación, Universidades, Ciencia y Sociedad digital, Valencia, Spain (Grant GV/2020/071).

      Appendix A. Supplementary data

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