A meta-analysis and a functional study support the influence of mtDNA variant m.16519C on the risk of rapid progression of knee osteoarthritis

[Abstract] Objectives: To identify mitochondrial DNA (mtDNA) genetic variants associated with the risk of rapid progression of knee osteoarthritis (OA) and to characterise their functional significance using a cellular model of transmitochondrial cybrids. Methods: Three prospective cohorts contributed participants. The osteoarthritis initiative (OAI) included 1095 subjects, the Cohort Hip and Cohort Knee included 373 and 326 came from the PROspective Cohort of Osteoarthritis from A Coruña. mtDNA variants were screened in an initial subset of 450 subjects from the OAI by in-depth sequencing of mtDNA. A meta-analysis of the three cohorts was performed. A model of cybrids was constructed to study the functional consequences of harbouring the risk mtDNA variant by assessing: mtDNA copy number, mitochondrial biosynthesis, mitochondrial fission and fusion, mitochondrial reactive oxygen species (ROS), oxidative stress, autophagy and a whole transcriptome analysis by RNA-sequencing. Results: mtDNA variant m.16519C is over-represented in rapid progressors (combined OR 1.546; 95% CI 1.163 to 2.054; p=0.0027). Cybrids with this variant show increased mtDNA copy number and decreased mitochondrial biosynthesis; they produce higher amounts of mitochondrial ROS, are less resistant to oxidative stress, show a lower expression of the mitochondrial fission-related gene fission mitochondrial 1 and an impairment of autophagic flux. In addition, its presence modulates the transcriptome of cybrids, especially in terms of inflammation, where interleukin 6 emerges as one of the most differentially expressed genes. Conclusions: The presence of the mtDNA variant m.16519C increases the risk of rapid progression of knee OA. Among the most modulated biological processes associated with this variant, inflammation and negative regulation of cellular process stand out. The design of therapies based on the maintenance of mitochondrial function is recommended

Validation of the OMNI-GSE subjective perceived exertion scale for controlling the global intensity in multi-purpose sessions in elderly people

El objetivo del presente trabajo es el de validar el uso de la escala de percepción del esfuerzo OMNI-GSE (escala OMNI- Global Session in the Elderly, rango: 0-10) en personas mayores para el control de la intensidad global durante sesiones con objetivos múltiples. Para este estudio se evaluaron20 sujetos mayores de 60 años (10 hombres y 10 mujeres), con una buena condición física y un mínimo de 18 meses de participación sistemática en programas específicos de actividad física para personas mayores. Todos los sujetos estaban familiarizados con el uso de la escala propuesta y realizaron 3 sesiones estandarizadas de 60 minutos, ejecutadas de forma aleatoria, en los que se controló la frecuencia cardiaca mediante un pulsómetro: 1) intensidad baja (RPE ≈ 4), moderada (RPE ≈ 6) y alta (RPE ≈ 8). La sesión fue administrada por un especialista con más de 3 años de trabajo con personas mayores. La sesión consistía en: a). ejercicio de movilidad articular (5 min); b). ejercicios de equilibrio y propioceptivos (5 min) c). ejercicios de agilidad (5 min); d). ejercicios de fuerza funcionales (15 min); e). ejercicios de resistencia (25 min) y f). ejercicios estáticos de estiramientos (5 min). Inmediatamente después de terminar la sesión se les ha pedido que señalasen, en una escala numérica y con apoyo visual de imágenes, su percepción subjetiva de la intensidad de la sesión. Los valores de la escala mostraron una correlación positiva con el trabajo cardiaco (total de latidos de las sesiones): correlación de 0,86 (r 2 = 0,74) en la sesión de intensidad baja; de 0,91 (r 2 = 0,83) en la sesión intensidad moderada; de 0,93 (r 2 = 0,86) en la sesión de intensidad alta. En conclusión, los presentes hallazgos demuestran que la escala diseñada puede ser usada para el control de la intensidad global de una sesión con objetivos múltiples en personas mayores experimentadas en este tipo de sesiones.The purpose of the present study was to validate the use of the OMNI-GSE (OMNI- Global Session in the Elderly, range: 0-10) perceived exertion scale in the elderly for controlling the global intensity during multi-purpose sessions. Twenty elderly subjects aged 60 and over (10 males and 10 females), all in good physical condition withat least 18months of participation in specific programs of physical activity for elderly people. All of them were familiarized with the use of the proposed scale. They performed 3 standardized sessions of 60 minutes, performed in random order, in which heart rate was controlled by means of a heart rate monitor: 1) low-intensity (RPE ≈ 4), moderate-intensity (RPE ≈ 6) and high-intensity (RPE ≈ 8). Sessions were controlled by a specialist with over 3 years of experience in working with elder people. Each session consisted of: a). mobility exercises (5 min); b). balance and proprioception exercises (5 min) c). agility exercises (5 min); d). functional strength exercises (15 min); e). endurance exercises (25 min) and f). static stretching exercises (5 min). Immediately after the end of the session, subjects were asked to point in a numeric scale and with the visual support of the images, their subjective perception of the session’s intensity. The values of the scale showed positive correlation with cardiac output(total of heartbeats in each session): correlation of 0,86 (r 2 = 0,74) for the low-intensity session; of 0,91 (r 2 = 0,83) for the moderate-intensity session; and of 0,93 (r 2 = 0,86) for the high-intensity session. The present findings suggest that the designed scale may be used to efficiently control the global intensity of a multiple objective session in elderly people with previous experience in this type of session.Sin financiaciónNo data 201