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

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.

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 influence 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 independently and negatively associated with relative STS power, supporting the potential role of GDF15 as a sensitive biomarker of frailty in older people.

Associations between inflammatory markers, body composition, and physical function: the Copenhagen Sarcopenia Study.

BACKGROUND: Chronic low-grade inflammation has been suggested as one of the key elements in the development of sarcopenia, but in contrast to disease-related loss of muscle mass, the role of chronic low-grade inflammation in age-related (primary) sarcopenia is still not clear. The aim of this study was to investigate low-grade inflammation in relation to age and the potential association between inflammatory biomarkers and body composition, muscle strength and physical performance in a healthy Danish cohort. METHODS: There were 1160 generally healthy men and women (range: 22-93 years) included. Appendicular lean mass (ALM) and visceral fat normalized to height (kg/m2 ) was assessed by dual-energy X-ray absorptiometry (iDXA, GE Lunar). Muscle strength and physical performance were evaluated by handgrip strength (HGS), 30 s sit-to-stand performance, and maximal gait speed (GS). Systemic levels of TNF-α, IL-6, IL-1ß, IL-4, IL-13, and IFN-γ were measured using multiplex bead-based immunoassays (Bio-Rad). hsCRP was assessed using latex particle-enhanced immunoturbidimetric assays (Roche Diagnostics). RESULTS: With age, ALM/h2 , HGS, sit-to-stand performance and GS decreased, whereas visceral fat/h2 increased in both men and women (P < 0.05). Systemic levels of hsCRP, TNF-α, IL-4, and IFN-γ increased with age in men and women (P < 0.05), while IL-1ß increased in women only (P < 0.01). Higher levels of hsCRP were associated with lower ALM/h2 in elderly (≥65 years) men and women (P < 0.001). Higher levels of hsCRP were associated with lower handgrip strength in elderly women (P < 0.05) whereas higher levels of hsCRP was not associated with lower HGS in elderly men (P = 0.056). Higher levels of hsCRP were associated with lower GS (P < 0.05), whereas IFN-γ was positively associated with GS in elderly women (P < 0.05), but not elderly men. Visceral fat index was positively associated with hsCRP in elderly men and women (P < 0.001). Compared with elderly with normal HGS, elderly men and women with low HGS displayed higher levels of TNF-α and hsCRP (P < 0.05). CONCLUSIONS: With age, systemic levels of hsCRP, TNF-α, IL-4, and IFN-γ increased, with hsCRP and TNF-α being especially elevated in more physically frail elderly supporting the association between low-grade systemic inflammation and poor physical function. In contrast, only high levels of hsCRP were weakly associated with low muscle mass and positively associated with visceral fat and low physical function, suggesting that chronic low-grade inflammation is not the main driver of age-related loss of muscle mass as previously suggested.

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 reported: 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 collected 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 counterparts (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 associated 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.

'Fat but powerful' paradox: association of muscle power and adiposity markers with all-cause mortality in older adults from the EXERNET multicentre study.

OBJECTIVES: To assess the influence of muscle power and adiposity on all-cause mortality risk and to evaluate the 'fat but powerful' (F+P) (or 'fat but fit') paradox in older adults. METHODS: A total of 2563 older adults (65‒91 years old) from the EXERNET multicentre study were included. Adiposity (body mass index (BMI), waist circumference, body fat percentage (BF%) and fat index), allometric and relative power (sit-to-stand muscle power test) and various covariates (age, sex, hypertension, smoking status and walking and sitting times per day) were registered at baseline. All-cause mortality was recorded during a median follow-up of 8.9 years. Participants were classified into four groups: lean and powerful (L+P), F+P, lean but weak and fat and weak (F+W). Cox proportional hazard regression models and adjusted HRs were calculated. RESULTS: According to BMI and waist circumference, all-cause mortality risk was reduced in the F+P (HR=0.55 and 0.63, p=0.044 and 0.049, respectively) and L+P (HR=0.57 and 0.58, p=0.043 and 0.025, respectively) groups. According to BF%, all-cause mortality decreased in the L+P group (HR=0.53; p=0.021), and a trend for a reduction was reported in the F+P group (HR=0.57; p=0.060). According to fat index, a survival benefit was only noted in the L+P group (HR=0.50; p=0.049). Higher levels of relative power reduced all-cause mortality risk among older people (HR=0.63 and 0.53, p=0.006 and 0.011, respectively). CONCLUSION: Powerful older people exhibited a reduced 9-year all-cause mortality regardless of BMI, waist circumference and BF%. Obesity according to fat index blunted the survival benefits of being powerful.

The Copenhagen Sarcopenia Study: lean mass, strength, power, and physical function in a Danish cohort aged 20-93 years.

BACKGROUND: Despite no international consensus on the diagnostic criteria for sarcopenia, low lean mass, muscle strength, and physical function are important risk factors for disability, frailty, and mortality in older individuals, as well as in a wide range of patients with muscle loss. Here, we provide a population-based reference material of total and regional lean body mass, muscle strength/power parameters, and physical function in a healthy cohort of Danish men and women across the lifespan. METHODS: Volunteers aged 20-93 years from the Copenhagen City Heart Study were invited to establish a Danish reference material (Copenhagen Sarcopenia Study) on lean mass characteristics [appendicular lean mass (ALM), iDXA, GE Lunar], muscle function [handgrip strength (HGS), Jamar dynamometer and leg extension power (LEP), Nottingham Power Rig], and physical function [30 s sit-to-stand test (STS), 10-m maximal and habitual gait speed (GS)]. RESULTS: A total of 1305 participants [729 women (age: 56.4 ± 18.9 years, height: 1.66 ± 0.01 m, body mass index: 24.6 ± 4.3 kg/m2 and 576 men, age: 57.0 ± 17.5 years, height: 1.80 ± 0.07 m, body mass index: 26.0 ± 3.9 kg/m2 ] completed all measurements and were included in the present analysis. Lean mass characteristics (TLM, ALM, and ALM/h2 ) decreased with increasing age in both men and women (P < 0.001). Men demonstrated larger absolute and relative total ALM and higher HGS and LEP compared with women at all age intervals (P < 0.001). HGS and LEP decreased progressively with age in both men and women (P < 0.01); 30 s STS performance, habitual GS, and maximal GS decreased at an accellerated rate of decline with increasing age in both men and women (P < 0.001). Habitual GS was reduced in men and women aged ≥70 years, while maximal GS was reduced from the age of ≥60 years compared with young adults (P < 0.001). Regardless of sex, 30 s STS was reduced from the age of ≥50 years compared with the young reference group (P < 0.001) CONCLUSIONS: While the power-based measurements (LEP and 30 s STS) started to decline already at age +50 years, less power-based parameters (GS and HGS) and lean mass characteristics (TLM, ALM, and ALM/h2 ) remained unaltered until after the age of +70 years. Notably, the cut-off thresholds derived in the present study differed from earlier reference data, which underlines the importance of obtaining updated and local reference materials.