Alteration of mitochondrial oxidative phosphorylation in aged skeletal muscle involves modification of adenine nucleotide translocator

AbstractThe process of skeletal muscle aging is characterized by a progressive loss of muscle mass and functionality. The underlying mechanisms are highly complex and remain unclear. This study was designed to further investigate the consequences of aging on mitochondrial oxidative phosphorylation in rat gastrocnemius muscle, by comparing young (6 months) and aged (21 months) rats. Maximal oxidative phosphorylation capacity was clearly reduced in older rats, while mitochondrial efficiency was unaffected. Inner membrane properties were unaffected in aged rats since proton leak kinetics were identical to young rats. Application of top-down control analysis revealed a dysfunction of the phosphorylation module in older rats, responsible for a dysregulation of oxidative phosphorylation under low activities close to in vivo ATP turnover. This dysregulation is responsible for an impaired mitochondrial response toward changes in cellular ATP demand, leading to a decreased membrane potential which may in turn affect ROS production and ion homeostasis. Based on our data, we propose that modification of ANT properties with aging could partly explain these mitochondrial dysfunctions

A Therapeutic Vibrating Insole Device for Postural Instability in Older People with Type 2 Diabetes: A Randomized Control Study

Introduction Frail older people with diabetes often present with or develop walking impairments, in part due to lower-limb sensory-motor neuropathy. Several studies suggest a possible improvement of balance control using somatosensory stimulation. We undertook a novel randomized control trial, the aim of which was to observe whether use of this device for 1 month improves walking speed as measured in the 10-m fast walking speed test standardized to body size at month 1 (M1) (FWS). Secondary outcomes were the differences between intervention (VS) and control (C) in the 10-m normal walking speed test, step length, short physical performance battery, timed up and go test, and posturographic measures. Methods Subjects were aged ≥ 70 years and had had type 2 diabetes for at least 2 years. The intervention (VS) at home consisted of 22-min daily vibrating sequences with noise intensity set at 90% of the tactile threshold for each foot. The same device was used in group C but noise was set to 0. Compliance was retrieved from the device. Results Among 56 subjects, 27 were in the VS group and 29 in the C group; 35 subjects were frail, 15 were prefrail ,and 6 were non-frail. Bilateral neuropathy was present in 17 subjects. More than half of sessions were done in 36 subjects with no discernible difference according to intervention. At M1 there were no discernible differences in FWS between the groups [VS: 0.96 (0.53) cm s−1 cm−1, C: 0.94 (0.47) cm s−1 cm−1]. There were also no discernible differences in other outcomes, irrespective of the presence of bilateral neuropathy. Conclusion In a cohort of frail, prefrail, or non-frail older subjects with diabetes, a 1-month intervention using a vibrating insole device did not alter measures of walking speed and related measures. Larger studies with longer term and different stimulation protocols are required to test this hypothesis more fully.Sponsorship was received for this study from EU 7th Framework Programme (contract no. 278803). CHU of Bordeaux paid the journal’s Rapid Service Fe

A Therapeutic Vibrating Insole Device for Postural Instability in Older People with Type 2 Diabetes: A Randomized Control Study

Introduction: Frail older people with diabetes often present with or develop walking impairments, in part due to lower-limb sensory-motor neuropathy. Several studies suggest a possible improvement of balance control using somatosensory stimulation. We undertook a novel randomized control trial, the aim of which was to observe whether use of this device for 1 month improves walking speed as measured in the 10-m fast walking speed test standardized to body size at month 1 (M1) (FWS). Secondary outcomes were the differences between intervention (VS) and control (C) in the 10-m normal walking speed test, step length, short physical performance battery, timed up and go test, and posturographic measures. Methods: Subjects were aged ≥ 70 years and had had type 2 diabetes for at least 2 years. The intervention (VS) at home consisted of 22-min daily vibrating sequences with noise intensity set at 90% of the tactile threshold for each foot. The same device was used in group C but noise was set to 0. Compliance was retrieved from the device. Results: Among 56 subjects, 27 were in the VS group and 29 in the C group; 35 subjects were frail, 15 were prefrail ,and 6 were non-frail. Bilateral neuropathy was present in 17 subjects. More than half of sessions were done in 36 subjects with no discernible difference according to intervention. At M1 there were no discernible differences in FWS between the groups [VS: 0.96 (0.53) cm s-1 cm-1, C: 0.94 (0.47) cm s-1 cm-1]. There were also no discernible differences in other outcomes, irrespective of the presence of bilateral neuropathy. Conclusion: In a cohort of frail, prefrail, or non-frail older subjects with diabetes, a 1-month intervention using a vibrating insole device did not alter measures of walking speed and related measures. Larger studies with longer term and different stimulation protocols are required to test this hypothesis more fully

Effects of a physical activity programme to prevent physical performance decline in onco-geriatric patients: a randomized multicentre trial

Background Older adults with cancer experience negative long-term functional effects of both cancer and treatments. Exercise may minimize their age-related and cancer-related functional decline. Methods We conducted a multicentre open-label 12 month randomized clinical trial with two parallel arms including participants aged >= 70 years with lymphoma or carcinoma requiring curative treatment. The study started at the beginning of any phase of cancer treatment (surgery, chemotherapy, or radiotherapy). The usual care group (UCG) received the current national recommendations in physical activity (a guideline without specific counselling). The intervention group (IG) received 1 year phoned physical activity advice individually adapted to physical assessment (twice a month during the first 6 months and then monthly). The primary outcome was the proportion of subjects with a 1 year decreased short physical performance battery (SPPB) score of 1 point or more. Physical, cognitive, and clinical secondary outcomes were also investigated. Results We allocated 301 participants (age 76.7 +/- 5.0, female 60.6%) to each group. At baseline, the median SPPB was 10/12 in both groups. Breast was the most frequent tumour site (35.7%). After 1 year, 14.0% of participants in the UCG and 18.7% in the IG had a decrease in SPPB score of 1 point or more (P = 0.772). At 2 years, there was no difference in SPPB, gait speed, International Physical Activity Questionnaire score, and verbal fluency. Subgroup analyses after 2 years showed a decline in SPPB for 29.8% of UCG and 5.0% of IG breast cancer participants (P = 0.006), in 21.7% of UCG and 6.2% of IG female participants (P = 0.019), and in 24.5% of UCG and 11.1% of IG normal nutritional status participants (P = 0.009). Falls, hospitalization, institutionalization, and death rates were similar in both groups. Conclusions Personalized phoned physical activity advice had not reduced functional decline at 1 year but provided preliminary evidence that may prevent physical performance decline at 2 years in older adults with breast cancer.This work was funded by the National Hospital Program of Clinical Research (Programme Hospitalier de Recherche Clinique 2010) and sponsored by the University Hospital of Bordeaux (CHU Bordeaux). Haritz Arrieta was supported by a fellowship from University of the Basque Country (UPV/EHU)

Effectiveness of a multimodal intervention in functionally impaired older people with type 2 diabetes mellitus

Background: Type 2 diabetes, a highly prevalent chronic disease, is associated with increasing frailty and functional decline in older people. We aimed to evaluate the effectiveness of a multimodal intervention on functional performance in frail and pre-frail participants aged >= 70 years with type 2 diabetes mellitus. Methods: The MID-Frail study was a cluster-randomized multicenter clinical trial conducted in 74 trial sites across seven European countries. The trial recruited 964 participants who were aged >70 years [mean age in intervention group, 78.4 (SD 5.6) years, 49.2% male and 77.6 (SD 5.29) years, 52.4% male in usual care group], with type diabetes mellitus and determined to be frail or pre-frail using Fried's frailty phenotype. Participants were allocated by trial site to follow either usual care (UCG) or intervention procedures (IG). Intervention group participants received a multimodal intervention composed of (i) an individualized and progressive resistance exercise programme for 16 weeks; (ii) a structured diabetes and nutritional educational programme over seven sessions; and (iii) Investigator-linked training to ensure optimal diabetes care. Short Physical Performance Battery (SPPB) scores were used to assess change in functional performance at 12 months between the groups. An analysis of the cost-effectiveness of the intervention was undertaken using the incremental cost-effectiveness ratio (ICER). Secondary outcomes included mortality, hospitalization, institutionalization, quality of life, burden on caregivers, the frequency and severity of hypoglycaemia episodes, and the cost-effectiveness of the intervention. Results: After 12 months, IG participants had mean SPPB scores 0.85 points higher than those in the UCG (95% CI, 0.44 to 1.26, P < 0.0001). Dropouts were higher in frail participants and in the intervention group, but significant differences in SPPB between treatment groups remained consistent after sensitivity analysis. Estimates suggest a mean saving following intervention of 428.02 EUR (2016) per patient per year, with ICER analysis indicating a consistent benefit of the described health care intervention over usual care. No statistically significant differences between groups were detected in any of the other secondary outcomes. Conclusions: We have demonstrated that a 12 month structured multimodal intervention programme across several clinical settings in different European countries leads to a clinically relevant and cost-effective improvement in the functional status of older frail and pre-frail participants with type 2 diabetes mellitus

Metabolites

An altered amino acid metabolism has been described in frail older adults which may contribute to muscle loss and functional decline associated with frailty. In the present investigation, we compared circulating amino acid profiles of older adults with physical frailty and sarcopenia (PF&S, = 94), frail/pre-frail older adults with type 2 diabetes mellitus (F-T2DM, = 66), and robust non-diabetic controls ( = 40). Partial least squares discriminant analysis (PLS-DA) models were built to define the amino acid signatures associated with the different frailty phenotypes. PLS-DA allowed correct classification of participants with 78.2 ± 1.9% accuracy. Older adults with F-T2DM showed an amino acid profile characterized by higher levels of 3-methylhistidine, alanine, arginine, ethanolamine, and glutamic acid. PF&S and control participants were discriminated based on serum concentrations of aminoadipic acid, aspartate, citrulline, cystine, taurine, and tryptophan. These findings suggest that different types of frailty may be characterized by distinct metabolic perturbations. Amino acid profiling may therefore serve as a valuable tool for frailty biomarker discovery

Diabetes Mellitus and Cognition: A Pathway Analysis in the MEMENTO Cohort

OBJECTIVE: To assess the role of biomarkers of Alzheimer's Disease (AD), neurodegeneration and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition. METHODS: The study sample was derived from MEMENTO, a cohort of French adults recruited in memory clinics and screened for either isolated subjective cognitive complaints or mild cognitive impairment. Diabetes was defined based on blood glucose assessment, use of antidiabetic agent or self-report. We used structural equation modelling to assess whether latent variables of AD pathology (PET mean amyloid uptake, Aβ(42)/Aβ(40) ratio and CSF phosphorylated tau), SVD (white matter hyperintensities volume and visual grading), and neurodegeneration (mean cortical thickness, brain parenchymal fraction, hippocampal volume, and mean fluorodeoxyglucose uptake) mediate the association between diabetes and a latent variable of cognition (five neuropsychological tests), adjusting for potential confounders. RESULTS: There were 254 (11.1%) participants with diabetes among 2,288 participants (median age 71.6 years; 61.8% women). The association between diabetes and lower cognition was significantly mediated by higher neurodegeneration (standardized indirect effect: -0.061, 95% confidence interval: -0.089; -0.032), but not mediated by SVD and AD markers. Results were similar when considering latent variables of memory or executive functioning. CONCLUSION: In a large clinical cohort in the elderly, diabetes is associated with lower cognition through neurodegeneration, independently of SVD and AD biomarkers

Etude du diabète comme facteur de risque d'un accident vasculaire cérébral chez le sujet âgé dans l'étude des 3 Cités

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF