RESUMEN
The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD+ levels through perturbed NAD+ biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.
Asunto(s)
Envejecimiento/fisiología , Mitocondrias/patología , Músculo Esquelético/patología , NAD/biosíntesis , Sarcopenia/patología , Anciano , Anciano de 80 o más Años , Biopsia , Estudios de Casos y Controles , Metabolismo Energético/fisiología , Humanos , Jamaica , Masculino , Persona de Mediana Edad , Mitocondrias/metabolismo , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Oxidación-Reducción , Fosforilación Oxidativa , Estrés Oxidativo/fisiología , Proteostasis , Sarcopenia/etnología , Singapur , Reino UnidoRESUMEN
OBJECTIVE: To assess whether different trajectories of weight gain since birth influence bone mineral content (BMC) and areal bone mineral density (aBMD) at 7 years of age. STUDY DESIGN: We studied a subsample of 1889 children from the Generation XXI birth cohort who underwent whole-body dual-energy radiograph absorptiometry. Weight trajectories identified through normal mixture modeling for model-based clustering and labeled "normal weight gain," "weight gain during infancy," "weight gain during childhood," and "persistent weight gain" were used. Differences in subtotal BMC, aBMD, and size-corrected BMC (scBMC) at age 7 years according to weight trajectories were estimated through analysis of covariance. RESULTS: Compared with the "normal weight gain" trajectory, children in the remaining trajectories had significantly greater BMC, aBMD, and scBMC at age 7 years, with the strongest associations for "persistent weight gain" (girls [BMC: 674.0 vs 559.8 g, aBMD: 0.677 vs 0.588 g/cm2, scBMC: 640.7 vs 577.4 g], boys [BMC: 689.4 vs 580.8 g, aBMD: 0.682 vs 0.611 g/cm2, scBMC: 633.0 vs 595.6 g]). After adjustment for current weight, and alternatively for fat and lean mass, children with a "weight gain during childhood" trajectory had greater BMC and aBMD than those with a "normal weight gain" trajectory, although significant differences were restricted to girls (BMC: 601.4 vs 589.2 g, aBMD: 0.618 vs 0.609 g/cm2). CONCLUSION: Overall, children following a trajectory of persistent weight gain since birth had clearly increased bone mass at 7 years, but weight gain seemed slightly more beneficial when it occurred later rather than on a normal trajectory during the first 7 years of life.
Asunto(s)
Densidad Ósea/fisiología , Desarrollo Infantil/fisiología , Aumento de Peso/fisiología , Absorciometría de Fotón , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Estudios ProspectivosRESUMEN
OBJECTIVE: To examine when, where and how fractures occur in postmenopausal women. METHODS: We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3. RESULTS: Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68-86% of NHNV and 68-83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling. CONCLUSION: In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year.
Asunto(s)
Accidentes por Caídas , Fracturas de Cadera/epidemiología , Osteoporosis Posmenopáusica/epidemiología , Estaciones del Año , Factores de Edad , Anciano , Anciano de 80 o más Años , Fracturas de Cadera/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis Posmenopáusica/prevención & control , Estudios RetrospectivosRESUMEN
Osteoporosis constitutes a major public health problem through its association with age related fractures. Fracture rates are generally higher in caucasian women than in other populations. Important determinants include estrogen deficiency in women, low body mass index, cigarette smoking, alcohol consumption, poor dietary calcium intake, physical inactivity, certain drugs and illnesses. Thus, modification of physical activity and dietary calcium/vitamin D nutrition should complement high risk approaches. In addition, the recently developed WHO algorithm for evaluation of 10-year absolute risk of fracture provides a means whereby various therapies can be targeted cost-effectively to those at risk. Risk factors, together with bone mineral density (BMD) and biochemical indices of bone turnover, can be utilised to derive absolute risks of fracture and cost-utility thresholds at which treatment is justified. These data will provide the basis for translation into coherent public health strategies aiming to prevent osteoporosis both in individuals and in the general population.
Asunto(s)
Huesos/fisiología , Fracturas Óseas/etiología , Osteoporosis/etiología , Absorciometría de Fotón/métodos , Densidad Ósea/fisiología , Resorción Ósea/fisiopatología , Femenino , Fracturas Óseas/epidemiología , Humanos , Osteoporosis/diagnóstico , Osteoporosis/prevención & control , Medición de Riesgo/métodos , Factores de Riesgo , Tomografía Computarizada por Rayos X/métodos , Ultrasonografía/métodosRESUMEN
Osteoporosis constitutes a major public health problem through its association with age related fractures. Fracture rates are generally higher in caucasian women than in other populations. Important determinants include estrogen deficiency in women, low body mass index, cigarette smoking, alcohol consumption, poor dietary calcium intake, physical inactivity, certain drugs and illnesses. Thus, modification of physical activity and dietary calcium/vitamin D nutrition should complement high risk approaches. In addition, the recently developed WHO algorithm for evaluation of 10-year absolute risk of fracture provides a means whereby various therapies can be targeted cost-effectively to those at risk. Risk factors, together with bone mineral density (BMD) and biochemical indices of bone turnover, can be utilised to derive absolute risks of fracture and cost-utility thresholds at which treatment is justified. These data will provide the basis for translation into coherent public health strategies aiming to prevent osteoporosis both in individuals and in the general population.
La osteoporosis constituye un importante problema de salud pública debido a su asociación con fracturas relacionadas con la edad. Las tasas de fractura generalmente son más altas en mujeres caucásicas que en otros grupos poblacionales. Los principales determinantes incluyen deficiencia de estrógeno en mujeres, bajo índice de masa corporal, consumo de tabaco y alcohol, escaso consumo de calcio, inactividad física y algunas drogas y enfermedades. De este modo, la modificación de la actividad física y el consumo de nutrimentos con calcio y vitamina D deben complementar los tratamientos en alto riesgo. Además, el recientemente desarrollado algoritmo de la OMS para la evaluación de riesgo de fractura absoluto a 10 años constituye una herramienta que permite plantear eficientemente diversas terapias a aquellos que están en riesgo. Los factores de riesgo, junto con la densidad mineral ósea y los índices bioquímicos de regeneración ósea pueden utilizarse para obtener riesgos de fractura absolutos así como umbrales costo-utilidad que justifiquen el tratamiento. Estos datos proveerán una base para su traducción en estrategias de salud pública con la finalidad de prevenir la osteoporosis tanto en los individuos como en la población en general.