Ivan Bautmans

Chronic low-grade inflammation and age-related sarcopenia.

Purpose of reviewAge-related chronic low-grade inflammatory profile (CLIP) has been recognized as an important causative factor for sarcopenia. Here, we report the recent evidence concerning CLIP and sarcopenia. Recent findingsTwenty-one studies were included (12 observational, five interventional studies and four randomized controlled trials). Observational studies strengthen the association between CLIP and sarcopenia in cross-sectional and longitudinal designs. Interleukin (IL)-6 and tumour necrosis factor-&agr; are the most reported inflammatory parameters. Biopsy studies confirm the role of oxidative mechanisms, protein kinase B and nuclear factor kappa-light-chain-enhancer of activated B cells pathways and implicate stress response mechanisms and heat shock protein. Adipose tissue as source of inflammatory cytokines remains unclear and correction for fat mass is advisable in new research. Exercise interventions (both aerobic and resistance training) demonstrate beneficial effects on CLIP even in the absence of decreases in weight, BMI or fat mass. IL-6 is also released during exercise, in hormone-like fashion unrelated to inflammation, and exercise-induced IL-6 changes require careful interpretation. Soy supplementation in one study showed no influence on CLIP and no recent pharmacological trials were retrieved. SummaryAssociations between CLIP and sarcopenia are observed quite consistently and underlying mechanisms become apparent. Exercise remains the mainstay intervention to lower CLIP and counter sarcopenia. More research is warranted to unravel the exact dose–response relationship.

Quality of Life in Sarcopenia and Frailty

The reduced muscle mass and impaired muscle performance that define sarcopenia in older individuals are associated with increased risk of physical limitation and a variety of chronic diseases. They may also contribute to clinical frailty. A gradual erosion of quality of life (QoL) has been evidenced in these individuals, although much of this research has been done using generic QoL instruments, particularly the SF-36, which may not be ideal in older populations with significant comorbidities. This review and report of an expert meeting presents the current definitions of these geriatric syndromes (sarcopenia and frailty). It then briefly summarizes QoL concepts and specificities in older populations and examines the relevant domains of QoL and what is known concerning QoL decline with these conditions. It calls for a clearer definition of the construct of disability, argues that a disease-specific QoL instrument for sarcopenia/frailty would be an asset for future research, and discusses whether there are available and validated components that could be used to this end and whether the psychometric properties of these instruments are sufficiently tested. It calls also for an approach using utility weighting to provide some cost estimates and suggests that a time trade-off study could be appropriate.

Motivators and barriers for physical activity in the oldest old: A systematic review

Worldwide, people engage insufficiently in physical activity, particularly subjects aged 80 years and over. For optimal life-style campaigns, knowledge of motivators and barriers for physical activity is mandatory. Given their specific needs, it is conceivable that these would be different for the oldest old compared to younger subjects. Pubmed, Web of Science and Psychinfo were systematically screened for articles reporting motivators and barriers for physical activity. Papers were excluded if data regarding elderly aged >79 years were absent. Forty-four relevant articles were included, involving a total of 28,583 subjects. Sixty one motivators and 59 barriers for physical activity in the elderly were identified, including those who are relevant for persons aged 80 years and over. Based on the results of our literature review, we recommend that when promoting physical activity in the oldest old, special attention is paid to the health benefits of physical activity, to the subjects fears, individual preferences and social support, and to constraints related to the physical environment. However, no studies were found exclusively describing people aged 80 years and over, and future research is necessary to differentiate the barriers or motivators that are specific for the oldest old from those of younger elderly.

Reliability and clinical correlates of 3D-accelerometry based gait analysis outcomes according to age and fall-risk

PURPOSE To investigate the reliability of a 3D-accelerometry based gait analysis, and its correlates with clinical status and fall-risk. METHODS Forty elderly subjects presenting with increased fall-risk (OFR), 41 elderly controls (OC) and 40 young controls (aged 80.6±5.4, 79.1±4.9 and 21.6±1.4 years respectively) underwent three gait evaluations (two assessors in random order) each containing two walks of 18 m with a DynaPort MiniMod accelerometer on the pelvis. Intra- and inter-observer reliability of gait speed, step-time asymmetry, mediolateral and craniocaudal step and stride regularity were determined by ICC and CV of standard error of measurement (CV(SEM)). Relationships with cognition (MMSE), dependency, grip strength, muscle endurance, and fall-risk (fall-history, timed-get-up-and-go and Tinetti-test) were analysed in elderly participants. RESULTS Reliability for single walk was low (ICC<0.70, 11%<CV(SEM)<23%), except for mediolateral step regularity (0.70≤ICC<0.80) and gait speed (ICC>0.80, CV(SEM)<7%), but high (ICC>0.70, 4%<CV(SEM)<20%) when based on the mean of two walks; except for step-time asymmetry (42%<CV(SEM)<77%). Compared to OC, OFR showed significantly (p<0.05) slower gait speed, and worse step and stride regularity. Gait speed, step-time asymmetry, step and stride regularity related significantly (p<0.05) with several functional outcomes. Besides gait speed (1.158 m/s, 78% sensitivity and 78% specificity), none of the gait features showed sufficient discriminative capacity according to fall-risk. CONCLUSIONS In all participants together, 3D-accelerometry based gait speed and regularity showed high reliability when based on two walks of 18 m. Relationships with functional characteristics support the validity of gait variability features in elderly persons. More fundamental and prospective research is necessary to clarify their clinical value.

Strength training at high versus low external resistance in older adults: Effects on muscle volume, muscle strength, and force–velocity characteristics

Muscle adaptations can be induced by high-resistance exercise. Despite being potentially more suitable for older adults, low-resistance exercise protocols have been less investigated. We compared the effects of high- and low-resistance training on muscle volume, muscle strength, and force-velocity characteristics. Fifty-six older adults were randomly assigned to 12 weeks of leg press and leg extension training at either HIGH (2×10-15 repetitions at 80% of one repetition maximum (1RM)), LOW (1×80-100 repetitions at 20% of 1RM), or LOW+ (1×60 repetitions at 20% of 1RM, followed by 1×10-20 repetitions at 40% of 1RM). All protocols ended with muscle failure. Leg press and leg extension of 1RM were measured at baseline and post intervention and before the first training session in weeks 5 and 9. At baseline and post intervention, muscle volume (MV) was measured by CT-scan. A Biodex dynamometer evaluated knee extensor static peak torque in different knee angles (PT(stat90°), PT(stat120°), PT(stat150°)), dynamic peak torque at different speeds (PT(dyn60°s)(-1), PT(dyn180°s)(-1), PT(dyn240°s)(-1)), and speed of movement at 20% (S20), 40% (S40), and 60% (S60) of PTstat90°. HIGH and LOW+ resulted in greater improvements in 1RM strength than LOW (p<0.05). These differences were already apparent after week 5. Similar gains were found between groups in MV, PT(stat), PT(dyn60°s)(-1), and PT(dyn180°s)(-1). No changes were reported in speed of movement. HIGH tended to improve PT(dyn240°s)(-1) more than LOW or LOW+ (p=0.064). In conclusion, high- and low-resistance exercises ending with muscle failure may be similarly effective for hypertrophy. High-resistance training led to a higher increase in 1RM strength than low-resistance training (20% of 1RM), but this difference disappeared when using a mixed low-resistance protocol in which the resistance was intensified within a single exercise set (40% of 1RM). Our findings support the need for more research on low-resistance programs in older age, in particular long-term training studies and studies focusing on residual effects after training cessation.

Circulating Heat Shock Protein 70 in Health, Aging and Disease

BackgroundHeat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context. Therefore, the objectives of this study were to investigate the effect of age and disease on circulating Hsp70 and, in particular, to evaluate the association between circulating Hsp70 and inflammatory parameters.ResultsSerum Hsp70, Interleukin (IL) -10, IL-6 and Tumor Necrosis Factor (TNF) alpha concentrations were determined in 90 hospitalised geriatric patients (aged 83 ± 6 years) and in 200 community-dwelling control subjects (100 elderly, aged 74 ± 5 years, and 100 young, aged 23 ± 3 years). In the community-dwelling elderly, serum Hsp70 and IL-10 concentrations were significantly lower and IL-6 was significantly higher when compared to healthy young control subjects. Elderly patients presenting inflammation (CRP serum levels ≥5 mg/L) showed significantly (p = 0.007) higher Hsp70 values; and Hsp70 correlated positively (p < 0.001) with IL-6 and CRP, but not with TNF-alpha or IL-10. A significant association was also noted between Hsp70 levels and the degree of dependency and cognitive decline in geriatric patients.ConclusionsThe present data provide new evidence that serum concentration of Hsp70 decreases with age in a normal population. Our study also shows that higher levels of Hsp70 are associated with inflammation and frailty in elderly patients.

Effect of advanced glycation end product intake on inflammation and aging: a systematic review

Aging is associated with a chronic low-grade inflammatory status that contributes to chronic diseases such as age-related muscle wasting, kidney disease, and diabetes mellitus. Since advanced glycation end products (AGEs) are known to be proinflammatory, this systematic review examined the relation between the dietary intake of AGEs and inflammatory processes. The PubMed and Web of Science databases were screened systematically. Seventeen relevant studies in humans or animals were included. The intervention studies in humans showed mainly a decrease in inflammation in subjects on a low-AGE diet, while an increase in inflammation in subjects on a high-AGE diet was less apparent. About half of the observational studies found a relationship between inflammatory processes and AGEs in food. When the results are considered together, the dietary intake of AGEs appears to be related to inflammatory status and the level of circulating AGEs. Moreover, limiting AGE intake may lead to a decrease in inflammation and chronic diseases related to inflammatory status. Most of the trials were conducted in patients with chronic kidney disease or diabetes, and thus additional studies in healthy individuals are needed. Further investigation is needed to elucidate the effects of lifetime exposure of dietary AGEs on aging and health.

Muscle Endurance in Elderly Nursing Home Residents Is Related to Fatigue Perception, Mobility, and Circulating Tumor Necrosis Factor‐Alpha, Interleukin‐6, and Heat Shock Protein 70

OBJECTIVES: To explore the relationships between muscle endurance and circulating interleukin (IL)‐6, tumor necrosis factor alpha (TNF‐α), and heat shock protein (Hsp)70 in nursing home residents and to assess how muscle endurance relates to self‐perceived fatigue and mobility.

SARCOPENIA AND FUNCTIONAL DECLINE: PATHOPHYSIOLOGY, PREVENTION AND THERAPY

Abstract Twenty years ago, the term ‘sarcopenia’ has been introduced to describe the ageing related loss of skeletal muscle mass. Since then, sarcopenia has been intensively studied and prevalence values have been reported in fifteen papers covering several continents and races. However, consistency regarding the outcome measures and corresponding cut-off values defining sarcopenia is lacking. Most approaches are based on estimations of muscle mass and proposed cut-off values might be too strict, thus reducing their use in daily practice. From a clinical viewpoint, the assessment of muscle performance (grip strength and endurance) can be proposed as a screening tool showing sufficient sensitivity. The pathophysiology of sarcopenia is multifactorial, and important changes at the tissue level have been identified. Close relationships with inflammatory processes have been demonstrated and there is strong evidence for the involvement of a chronic low-grade inflammatory activity. Sarcopenia is aggravated by a complex interaction of several factors among which aging, disuse, immobilization, disease and malnutrition. A comprehensive geriatric assessment should allow the clinician to estimate the relative contribution of these factors and to elaborate appropriate management. From all interventions studied, intensive resistance training seems the most efficient to counter sarcopenia, even in the very old geriatric patients. Significant ameliorations (up to >50% strength gain) can be expected after six weeks of training at a rhythm of 2-3 sessions per week. From a preventive viewpoint, all elderly patients should be advised to start such an exercise program and continue it as long as possible. To date, most pharmacological interventions to counter sarcopenia include drugs with anabolic effects. Unfortunately, their effect is questionable and no clear guidelines exist for the prescription of these products in the context of sarcopenia.

No influence of noradrenaline manipulation on acute exercise-induced increase of brain-derived neurotrophic factor.

PURPOSE To examine the influence of a selective noradrenaline reuptake inhibitor (SNRI) on the exercise-induced increase in circulating brain-derived neurotrophic factor (BDNF). METHODS In a double-blind, placebo-controlled, crossover design, 11 young, healthy male subjects were treated with either placebo or reboxetine. On each occasion, they performed a 60-min cycling exercise at 55% of their maximal power output (Wmax) followed by a time trial (TT) at 75% of Wmax. HR and ratings of perceived exertion were measured. Blood samples were taken at four time points. RESULTS An increase in serum BDNF was found after exercise without any influence of drug administration on BDNF levels. Serum BDNF returned to resting levels after 15 min of recovery. Time trial (TT) performance was significantly worse after reboxetine intake. Serum cortisol increased in both trials during and after exercise and was significantly higher in the reboxetine trial. Also, HR was increased with reboxetine intake, probably because of the sympathomimetic effect of SNRI. Midterm memory was significantly impaired after the exercise protocol without difference between reboxetine and placebo trial. CONCLUSIONS The administration of an SNRI has no effect on the exercise-induced increase in BDNF. However, effects were seen on serum cortisol, HR, and memory. Future research should focus on the effect of regular exercise training in combination with several reuptake inhibitors in both healthy and depressed subjects on BDNF and memory.