Changes in systemic GDF15 across the adult lifespan and their impact on maximal muscle power: the Copenhagen Sarcopenia Study

Background Although growth differentiation factor 15 (GDF15) is known to increase with disease and is associated with low physical performance, the role of GDF15 in normal ageing is still not fully understood. Specifically, the influ ence of circulating GDF15 on impairments in maximal muscle power (a major contributor to functional limitations) and the underlying components has not been investigated. Methods Data from 1305 healthy women and men aged 20 to 93 years from The Copenhagen Sarcopenia Study were analysed. Circulating levels of GDF15 and markers of inflammation (tumor necrosis factor-alpha, interleukin-6, and high-sensitivity C-reactive protein) were measured by ELISA (R&D Systems) and multiplex bead-based immunoassays (Bio-Rad). Relative (normalized to body mass), allometric (normalized to height squared), and specific (normalized to leg muscle mass) muscle power were assessed by the Nottingham power rig [leg extension power (LEP)] and the 30 s sit-to-stand (STS) muscle power test. Total body fat, visceral fat, and leg lean mass were assessed by dual energy X-ray absorptiometry. Leg skeletal muscle index was measured as leg lean mass normalized to body height squared. Results Systemic levels of GDF15 increased progressively as a function of age in women (1.1 ± 0.4 pg·mL 1 ·year 1 ) and men (3.3 ± 0.6 pg·mL 1 ·year 1 ) (both P < 0.05). Notably, GDF15 increased at a faster rate from the age of 65 years in women (11.5 ± 1.2 pg·mL 1 ·year 1 , P < 0.05) and 70 years in men (19.3 ± 2.3 pg·mL 1 ·year 1 , P < 0.05), resulting in higher GDF15 levels in men compared with women above the age of 65 years (P < 0.05). Independently of age and circulatory markers of inflammation, GDF15 was negatively correlated to relative STS power (P < 0.05) but not LEP, in both women and men. These findings were mainly explained by negative associations of GDF15 with specific STS power in women and men (both P < 0.05). Conclusions A J-shaped relationship between age and systemic GDF15 was observed, with men at older age showing steeper increases and elevated GDF15 levels compared with women. Importantly, circulating GDF15 was indepen dently and negatively associated with relative STS power, supporting the potential role of GDF15 as a sensitive biomarker of frailty in older people

Response to commentary on “The sit-to-stand muscle power test: An easy, inexpensive and portable procedure to assess muscle power in older people”

Our STS power equation does not aim to substitute “gold standard” methods, and does not provide data that can be interchangeable with those yielded by comprehensive kinematic and kinetic analyses; however, it provides the possibility to assess lower-limb muscle power in contexts in which time or resources constrains inherent to traditional instruments may prevent its assessment

Neuromuscular adaptations after 12 weeks of light- vs. heavy-load power-oriented resistance training in older adults

This study aimed to determine the specific adaptations provoked by power oriented resistance training using light (LL-PT, 40% 1-RM) vs. heavy (HL-PT, 80% 1-RM) loads in older adults. Using a randomized within-subject study design, 45 older adults (>65 years) completed an 8-week control period (CTR) followed by 12 weeks of unilateral LL-PT vs. HL-PT on a leg press. The 1-RM, theoretical force at zero velocity (F0), maximal unloaded velocity (V0), and maximal muscle power (Pmax) were determined through a force-velocity relationship test. Isometrically, the rate of force development (RFD) and the corresponding muscle excitation of the knee extensor muscles were assessed. In addition, muscle cross-sectional area (CSA) and architecture of two quadriceps muscles were determined. Changes after CTR, LL-PT and HL-PT were compared using linear mixed models. HL PT provoked greater improvements in 1-RM and F0 (effect size (ES) = 0.55‒0.68; p < 0.001) than those observed after LL-PT (ES = 0.27−0.47; p ≤ 0.001) (post hoc treatment effect, p ≤ 0.057). By contrast, ES of changes in V0 was greater in LL-PT compared to HL-PT (ES = 0.71, p < 0.001 vs. ES = 0.39, p < 0.001), but this differ ence was not statistically significant. Both power training interventions elicited a moderate increase in Pmax (ES = 0.65‒0.69, p < 0.001). Only LL-PT improved early RFD (ie, ≤100 ms) and muscle excitation (ES = 0.36‒0.60, p < 0.05). Increased CSA were noted after both power training programs (ES = 0.13‒0.35, p < 0.035), whereas pennation angle increased only after HL-PT (ES = 0.37, p = 0.004). In conclusion, HL-PT seems to be more effective in improving the capability to gen erate large forces, whereas LL-PT appears to trigger greater gains in movement velocity in older adults. However, both interventions promoted similar increases in muscle power as well as muscle hypertrophy

The Effect of the Stretch-Shortening Cycle in the Force–Velocity Relationship and Its Association With Physical Function in Older Adults With COPD

This study aimed to evaluate the effect of the stretch-shortening cycle (SSC) on different portions of the force–velocity (F–V) relationship in older adults with and without chronic obstructive pulmonary disease (COPD), and to assess its association with physical function. The participants were 26 older adults with COPD (79 ± 7 years old; FEV1 = 53 ± 36% of predicted) and 10 physically active non-COPD (77 ± 4 years old) older adults. The F–V relationship was evaluated in the leg press exercise during a purely concentric muscle action and compared with that following an eccentric muscle action at 10% intervals of maximal unloaded shortening velocity (V0). Vastus lateralis (VL) muscle thickness, pennation angle (PA), and fascicle length (FL) were assessed by ultrasound. Habitual gait speed was measured over a 4-m distance. COPD subjects exhibited lower physical function and concentric maximal muscle power (Pmax) values compared with the non-COPD group (both p &lt; 0.05). The SSC increased force and power values among COPD participants at 0–100 and 1–100% of V0, respectively, while the same was observed among non-COPD participants only at 40–90 and 30–90% of V0, respectively (all p &lt; 0.05). The SSC induced greater improvements in force, but not power, among COPD compared with non-COPD subjects between 50 and 70% of V0 (all p &lt; 0.05). Thus, between-group differences in muscle power were not statistically significant after the inclusion of the SSC (p &gt; 0.05). The SSC-induced potentiation at 50–100% of V0 was negatively associated with physical function (r = -0.40–0.50), while that observed at 80–100% of V0 was negatively associated with VL muscle thickness and PA (r = -0.43–0.52) (all p &lt; 0.05). In conclusion, older adults with COPD showed a higher SSC-induced potentiation compared with non-COPD subjects, which eliminated between-group differences in muscle power when performing SSC muscle actions. The SSC-induced potentiation was associated with lower physical function, VL muscle thickness, and VL PA values. The SSC-induced potentiation may help as a compensatory mechanism in those older subjects with a decreased ability to produce force/power during purely concentric muscle actions

Effects of Power-Oriented Resistance Training With Heavy vs. Light Loads on Muscle-Tendon Function in Older Adults: A Study Protocol for a Randomized Controlled Trial

Background: Power-oriented resistance training (PRT) is one of the most effective exercise programs to counteract neuromuscular and physical function age-related declines. However, the optimal load that maximizes these outcomes or the load-specific adaptations induced on muscle power determinants remain to be better understood. Furthermore, to investigate whether these adaptations are potentially transferred to an untrained limb (i.e., cross-education phenomenon) could be especially relevant during limb-immobilization frequently observed in older people (e.g., after hip fracture). Methods: At least 30 well-functioning older participants (>65 years) will participate in a within-person randomized controlled trial. After an 8-week control period, the effects of two 12-week PRT programs using light vs. heavy loads will be compared using an unilateral exercise model through three study arms (light-load PRT vs. non-exercise; heavy-load PRT vs. non-exercise; and light- vs. heavy- load PRT). Muscle-tendon function, muscle excitation and morphology and physical function will be evaluated to analyze the load-specific effects of PRT in older people. Additionally, the effects of PRT will be examined on a non-exercised contralateral limb. Discussion: Tailored exercise programs are largely demanded given their potentially greater efficiency preventing age-related negative consequences, especially during limb immobilization. This trial will provide evidence supporting the use of light- or heavy-load PRT on older adults depending on individual needs, improving decision making and exercise program efficacy. Clinical Trial Registration: NCT03724461 registration data: October 30, 2018

Relative sit-to-stand power cut-off points and their association with negatives outcomes in older adults

The purposes of this study were: (i) to evaluate the association of sit-to-stand (STS) power and body composition parameters [body mass index (BMI) and legs skeletal muscle index (SMI)] with age; (ii) to provide cut-off points for low relative STS power (STSrel), (iii) to provide normative data for well-functioning older adults and (iv) to assess the association of low STSrel with negative outcomes. Cross-sectional design (1369 older adults). STS power parameters assessed by validated equations, BMI and Legs SMI assessed by dual-energy X-ray absorptiometry were recorded. Sex- and age-adjusted segmented and logistic regression analyses and receiver operator characteristic curves were used. Among men, STSrel showed a negative association with age up to the age of 85 years (− 1.2 to − 1.4%year−1; p < 0.05). In women, a negative association with age was observed throughout the old adult life (− 1.2 to − 2.0%year−1; p < 0.001). Cut-off values for low STSrel were 2.5 W kg−1 in men and 1.9 W kg−1 in women. Low STSrel was associated with frailty (OR [95% CI] = 5.6 [3.1, 10.1]) and low habitual gait speed (HGS) (OR [95% CI] = 2.7 [1.8, 3.9]) in men while low STSrel was associated with frailty (OR [95% CI] = 6.9 [4.5, 10.5]) low HGS (OR [95% CI] = 2.9 [2.0, 4.1]), disability in activities of daily living (OR [95% CI] = 2.1 [1.4, 3.2]), and low quality of life (OR [95%CI] = 1.7 [1.2, 2.4]) in women. STSrel declined with increasing age in both men and women. Due to the adverse outcomes related to STSrel, the reported cut-off points can be used as a clinical tool to identify low STSrel among older adults

Relative sit‑to‑stand power cut‑of points and their association with negatives outcomes in older adults

The purposes of this study were: (i) to evaluate the association of sit-to-stand (STS) power and body composition parameters [body mass index (BMI) and legs skeletal muscle index (SMI)] with age; (ii) to provide cut-of points for low relative STS power (STSrel), (iii) to provide normative data for well functioning older adults and (iv) to assess the association of low STSrel with negative outcomes. Cross-sectional design (1369 older adults). STS power parameters assessed by validated equations, BMI and Legs SMI assessed by dual-energy X-ray absorptiometry were recorded. Sex- and age adjusted segmented and logistic regression analyses and receiver operator characteristic curves were used. Among men, STSrel showed a negative association with age up to the age of 85 years (− 1.2 to − 1.4%year−1; p < 0.05). In women, a negative association with age was observed throughout the old adult life (− 1.2 to − 2.0%year−1; p < 0.001). Cut-of values for low STSrel were 2.5W ­kg−1 in men and 1.9W ­kg−1 in women. Low STSrel was associated with frailty (OR [95% CI] = 5.6 [3.1, 10.1]) and low habitual gait speed (HGS) (OR [95% CI] = 2.7 [1.8, 3.9]) in men while low STSrel was associated with frailty (OR [95% CI] = 6.9 [4.5, 10.5]) low HGS (OR [95% CI] = 2.9 [2.0, 4.1]), disability in activities of daily living (OR [95% CI] = 2.1 [1.4, 3.2]), and low quality of life (OR [95%CI] = 1.7 [1.2, 2.4]) in women. STSrel declined with increasing age in both men and women. Due to the adverse outcomes related to STSrel, the reported cut-of points can be used as a clinical tool to identify low STSrel among older adults

Relative sit-to-stand power: aging trajectories, functionally relevant cut-off points, and normative data in a large European cohort

Background A validated, standardized, and feasible test to assess muscle power in older adults has recently been re ported: the sit-to-stand (STS) muscle power test. This investigation aimed to assess the relationship between relative STS power and age and to provide normative data, cut-off points, and minimal clinically important differences (MCID) for STS power measures in older women and men. Methods A total of 9320 older adults (6161 women and 3159 men) aged 60–103 years and 586 young and middle-aged adults (318 women and 268 men) aged 20–60 years were included in this cross-sectional study. Relative (normalized to body mass), allometric (normalized to height squared), and specific (normalized to legs muscle mass) muscle power values were assessed by the 30 s STS power test. Body composition was evaluated by dual energy X-ray absorptiometry and bioelectrical impedance analysis, and legs skeletal muscle index (SMI; normalized to height squared) was calculated. Habitual and maximal gait speed, timed up-and-go test, and 6 min walking distance were col lected as physical performance measures, and participants were classified into two groups: well-functioning and mobility-limited older adults. Results Relative STS power was found to decrease between 30–50 years ( 0.05 W·kg 1 ·year 1 ; P > 0.05), 50–80 years ( 0.10 to 0.13 W·kg 1 ·year 1 ; P < 0.001), and above 80 years ( 0.07 to 0.08 W·kg 1 ·year 1 ; P < 0.001). A total of 1129 older women (18%) and 510 older men (16%) presented mobility limitations. Mobility-limited older adults were older and exhibited lower relative, allometric, and specific power; higher body mass index (BMI) and legs SMI (both only in women); and lower legs SMI (only in men) than their well-functioning coun terparts (all P < 0.05). Normative data and cut-off points for relative, allometric, and specific STS power and for BMI and legs SMI were reported. Low relative STS power occurred below 2.1 W·kg 1 in women (area under the curve, AUC, [95% confidence interval, CI] = 0.85 [0.84–0.87]) and below 2.6 W·kg 1 in men (AUC [95% CI] = 0.89 [0.87–0.91]). The age-adjusted odds ratios [95% CI] for mobility limitations in older women and men with low relative STS power were 10.6 [9.0–12.6] and 14.1 [10.9–18.2], respectively. MCID values for relative STS power were 0.33 W·kg 1 in women and 0.42 W·kg 1 in men. Conclusions Relative STS power decreased significantly after the age of 50 years and was negatively and strongly as sociated with mobility limitations. Our study provides normative data, functionally relevant cut-off points, and MCID values for STS power for their use in daily clinical practice

Ten‐year longitudinal changes in muscle power, force, and velocity in young, middle‐aged, and older adults

Abstract Background Maximum muscle power (Pmax) is a biomarker of physical performance in all ages. No longitudinal studies have assessed the effects of aging on Pmax obtained from the torque‐velocity (T‐V) relationship, which should be considered the ‘gold standard’. This study evaluated the longitudinal changes in the T‐V relationship and Pmax of the knee‐extensor muscles in young, middle‐aged, and older adults after 10 years of follow‐up. Methods Four hundred eighty‐nine subjects (311 men and 178 women; aged 19–68 years) were tested at baseline and after a 10‐year follow‐up. Anthropometric data, daily protein intake, physical activity level (PAL), and knee‐extension muscle function (isometric, isokinetic, and isotonic) were evaluated. A novel hybrid equation combining a linear and a hyperbolic (Hill‐type) region was used to obtain the T‐V relationship and Pmax of the participants, who were grouped by sex and age (young: 20–40 years; middle‐aged: 40–60 years; and old: ≥60 years). Linear mixed‐effect models were used to assess effects of time, sex, and age on T‐V parameters, Pmax, and body mass index (BMI). Additional analyses were performed to adjust for changes in daily protein intake and PAL. Results Pmax decreased in young men (−0.6% per year; P < 0.001), middle‐aged men and women (−1.1% to −1.4% per year; P < 0.001), and older men and women (−2.2% to −2.4% per year; P ≤ 0.053). These changes were mainly related to decrements in torque at Pmax at early age and to decrements in both torque and velocity at Pmax at older age. BMI increased among young and middle‐aged adults (0.2% to 0.5% per year; P < 0.001), which led to greater declines in relative Pmax in those groups. S/T0, that is, the linear slope of the T‐V relationship relative to maximal torque, exhibited a significant decline over time (−0.10%T0·rad·s−1 per year; P < 0.001), which was significant among middle‐aged men and old men and women (all P < 0.05). Annual changes in PAL index were significantly associated to annual changes in Pmax (P = 0.017), so the overall decline in Pmax was slightly attenuated in the adjusted model (−5.26 vs. −5.05 W per year; both P < 0.001). Conclusions Pmax decreased in young, middle‐aged, and older adults after a 10‐year follow‐up. The early declines in Pmax seemed to coincide with declines in force, whereas the progressive decline at later age was associated with declines in both force and velocity. A progressively blunted ability to produce force, especially at moderate to high movement velocities, should be considered a specific hallmark of aging