The gut–muscle axis in older subjects with low muscle mass and performance: a proof of concept study exploring fecal microbiota composition and function with shotgun metagenomics sequencing

The gut microbiota could influence the pathophysiology of age‐related sarcopenia through multiple mechanisms implying modulation of chronic inflammation and anabolic resistance. The aim of this study was to compare the fecal microbiota composition and functionality, assessed by shotgun metagenomics sequencing, between two groups of elderly outpatients, differing only for the presence of primary sarcopenia. Five sarcopenic elderly subjects and twelve non‐sarcopenic controls, classified according to lower limb function and bioimpedance‐derived skeletal muscle index, provided a stool sample, which was analyzed with shotgun metagenomics approaches, to determine the overall microbiota composition, the representation of bacteria at the species level, and the prediction of bacterial genes involved in functional metabolic pathways. Sarcopenic subjects displayed different fecal microbiota compositions at the species level, with significant depletion of two species known for their metabolic capacity of producing short‐chain fatty acids (SCFAs), Faecalibacterium prausnitzii and Roseburia inulinivorans, and of Alistipes shahii. Additionally, their fecal metagenome had different representation of genes belonging to 108 metabolic pathways, namely, depletion of genes involved in SCFA synthesis, carotenoid and isoflavone biotransformation, and amino acid interconversion. These results support the hypothesis of an association between microbiota and sarcopenia, indicating novel possible mediators, whose clinical relevance should be investigated in future studies

The Interplay between Magnesium and Testosterone in Modulating Physical Function in Men

The role of nutritional status as determinant of successful aging is very well recognized. There is recent evidence that nutrition may exert its beneficial effects through the modulation of the hormonal anabolic milieu. Under-nutrition and anabolic hormonal deficiency frequently coexist in older individuals determining an increased risk of mobility impairment and adverse outcomes. Mineral dietary assessment has received attention as key component of the nutritional modulation of anabolic status and physical performance. There is evidence that several minerals, including magnesium, exert a positive influence on Insulin-like Growth Factor-1 (IGF-1) secretion in both sexes, and Testosterone (T) in men. In this review we summarize the existing knowledge about the mechanisms by which magnesium can affect T bioactivity in older men. Particular attention will be also devoted to the preliminary observational and intervention studies addressing the relationship between magnesium and T in adult and older individuals. We believe that, if larger studies will confirm these pivotal data, hormonal and mineral strategies might be adopted as synergistic treatment to approach the multifactorial nature of accelerated aging

Comprehensive Model for Physical and Cognitive Frailty: Current Organization and Unmet Needs

Aging is characterized by the decline and deterioration of functional cells and results in a wide variety of molecular damages and reduced physical and mental capacity. The knowledge on aging process is important because life expectancy is expected to rise until 2050. Aging cannot be considered a homogeneous process and includes different trajectories characterized by states of fitness, frailty, and disability. Frailty is a dynamic condition put between a normal functional state and disability, with reduced capacity to cope with stressors. This geriatric syndrome affects physical, neuropsychological, and social domains and is driven by emotional and spiritual components. Sarcopenia is considered one of the determinants and the biological substrates of physical frailty. Physical and cognitive frailty are separately approached during daily clinical practice. The concept of motoric cognitive syndrome has partially changed this scenario, opening interesting windows toward future approaches. Thus, the purpose of this manuscript is to provide an excursus on current clinical practice, enforced by aneddoctical cases. The analysis of the current state of the art seems to support the urgent need of comprehensive organizational model incorporating physical and cognitive spheres in the same umbrella

Handgrip strength predicts persistent walking recovery after hip fracture surgery

Background In older people, hip fractures often lead to disability and death. We evaluated handgrip strength, an objective measure of physical function for bedridden patients, as a predictor of walking recovery in the year after fracture surgery. Methods This multicenter prospective cohort study included 504 patients, aged 70 years or more, who were admitted to the hospital for hip fracture surgery and were formerly able to walk independently. A multidimensional geriatric evaluation that included a physical examination, Short Portable Mental Status Questionnaire, Geriatric Depression Scale, Charlson Index, Basic Activities of Daily Living, and grip strength was administered at the time of admission. Follow-ups were performed every 3 months for 1 year after surgery to assess functional status and survival. The walking recovery probability was evaluated using multivariable logistic regression models. Results The mean age of the participants was 85.3 ± 5.5 years, and 76.1% of the participants were women. The mean grip strength was greater in men (β: 6.6 ± 0.62, P <.001) and was directly related to the Short Portable Mental Status Questionnaire results (P <.001), Basic Activities of Daily Living results (P <.001), serum vitamin D levels (P =.03), and time before surgery (P <.001), whereas it was inversely related to age (P <.001), Geriatric Depression Scale score (P <.001), and Charlson Index (P <.001). After adjusting for confounders, the grip strength was directly associated with the probability of both incident and persistent walking recovery (odds ratio highest tertile vs lowest tertile, 2.84, confidence interval, 1.76-4.59 and 2.79, confidence interval, 1.35-5.79, respectively). Conclusions In older patients with hip fractures, early grip strength evaluation might provide important prognostic information regarding the patient's future functional trajectory. © 2013 Elsevier Inc. All rights reserved

Instrumental and non-instrumental evaluation of 4-meter walking speed in older individuals

Background: Manual measurement of 4-meter gait speed by a stopwatch is the gold standard test for functional assessment in older adults. However, the accuracy of this technique may be biased by several factors, including intra- and inter-operator variability. Instrumental techniques of measurement using accelerometers may have a higher accuracy. Studies addressing the concordance between these two techniques are missing. The aim of the present community-based observational study was to compare manual and instrumental measurements of 4-meter gait speed in older individuals and to assess their relationship with other indicators of physical performance. Methods: One-hundred seventy-two (69 men, 103 women) non-disabled community-dwellers aged \ue2\u89\ua565 years were enrolled. They underwent a comprehensive geriatric assessment including physical function by Short Physical Performance Battery (SPPB), hand grip strength, and 6-minute walking test (6MWT). Timed usual walking speed on a 4-meter course was assessed by using both a stopwatch (4-meter manual measurement, 4-MM) and a tri-axial accelerometer (4-meter automatic measurement, 4-MA). Correlations between these performance measures were evaluated separately in men and women by partial correlation coefficients. Results: In both genders, 4-MA was associated with 4-MM (men r = 0.62, p<0.001; women r = 0.73, p<0.001), handgrip strength (men r = 0.40, p = 0.005; women r = 0.29, p = 0.001) and 6MWT (men r = 0.50, p = 0.0004; women r = 0.22, p = 0.048). 4-MM was associated with handgrip strength and 6MWT in both men and women. Considering gait speed <0.6 m/s as diagnostic of dismobility syndrome, the two methods of assessment disagreed, with a different categorization of subjects, in 19% of men and 23% of women. The use of accelerometer resulted in 29 (13 M, 16 F) additional diagnoses of dismobility, compared with the 4-MM. Conclusions: In an older population, the concordance of gait speeds manually or instrumentally assessed is not optimal. The results suggest that manual measures might lead to misclassification of a substantial number of subjects. However, longitudinal studies using standardized and validated procedures aimed at the comparison of different techniques are needed before recommending the use of accelerometers in comprehensive geriatric assessment

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Determinants of cardiac structure in frail and sarcopenic elderly adults

Background: Cardiac structure and function change with age. The higher prevalence of left ventricular hypertrophy (LVH) with concentric remodeling is indicative of a typical geometric pattern of aging associated with a higher cardiovascular (CV) risk and diseases. The recent associations found between low left ventricular and skeletal mass in older patients with frailty and sarcopenia have raised great interest in investigating cardiac characteristics and determinants of left ventricular mass (LVM) in this population. Design: Cross-sectional study. Methods: We evaluated 100 sarcopenic and physically frail outpatients, 33 men (M), 67 women (F), aged ≥70 years (mean age 79 ± 5) and enrolled in the Parma site of European multicenter SPRINTT population. Results: All male and female participants showed LVH, assessed as indexed LVM to body surface area (LVM/BSA) (M = 128 ± 39 g/m2; F = 104 ± 26 g/m2), and were more prone to have concentric geometry, as demonstrated by relative wall thickness value (0.41 in both sexes). After backward regression analysis, including covariates such as age, sex, office or ABPM systolic blood pressure (SBP), heart rate, BSA, use of β blockers, ACE-inhibitors, angiotensin receptor blockers, calcium channel blockers, diuretics, physical activity, hemoglobin level, and Mini Mental State examination - the most powerful determinants of LVM were clinical SBP (β = 1.51 ± 0.31, p = 0.0005), BSA (β = 165.9 ± 41.4, p = 0.0001), while less powerful determinants were 24 h, daily and nightly SBP (p = 0.02, p = 0.002, p = 0.004 respectively). Conclusions: Older sarcopenic and physically frail patients showed LVH with a tendency towards concentric geometry. The main determinant of LVM was SBP, highlighting the key role that hemodynamic condition plays in determining LVH in this population

Perfluoroalkyl substances, sex hormones, and insulin-like growth factor-1 at 6–9 Years of age : a cross-sectional analysis within the C8 health project

Background: Exposure to some perfluoroalkyl substances (PFAS), such as perfluorohexane sulfonate (PFHxS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA), may alter levels of sex hormones and insulin-like growth factor-1 (IGF-1) in animals. Human studies on this topic are scarce and none have been conducted in young children. Objectives: To investigate the relationship between levels of PFAS and estradiol, total testosterone and IGF-1 in 2,292 children (aged 6-9 years) from the C8 Health Project living near a chemical plant in the Mid-Ohio Valley (USA) with local contamination from PFOA. Methods: Serum samples were collected in 2005-2006 and analyzed for PFAS, sex hormones and IGF-1. Results from regression models were expressed as the adjusted percentage difference (95% CI) per sex-specific interquartile range (IQR) increment of each PFAS serum concentration. Analyses by PFAS quartiles were also conducted. Results: Median concentrations of PFHxS, PFOA, PFOS, and PFNA were 8, 35, 22, and 1.7 ng/mL in boys and 7, 30, 21, and 1.7 ng/mL in girls. In boys, PFOA concentrations were significantly associated with testosterone levels (-4.9% [-8.7, -0.8%]); PFOS with estradiol (-4.0% [-7.7, -0.1%]), testosterone (-5.8% [-9.4, -2.0%]), and IGF-1 (-5.9% [-8.3, -3.3%]); and PFNA with IGF-1 (-3.5% [-6.0, -1.0%]). In girls, significant associations were found between PFOS and testosterone (-6.6% [-10.1, -2.8%]) and IGF-1 (-5.6% [-8.2, -2.9%]); and PFNA and IGF-1 (-3.8% [-6.4, -1.2%]). In both sexes, the magnitudes of the associations decreased monotonically across quartiles for testosterone and PFOS, and for IGF-1 and both PFOS and PFNA. Conclusions: To our knowledge, this is the first study suggesting that PFAS are associated with lowe