ABSTRACT
Gene expression in skeletal muscle of older individuals may reflect compensatory adaptations in response to oxidative damage that preserve tissue integrity and maintain function. Identifying associations between oxidative stress response gene expression patterns and mitochondrial function, physical performance, and muscle mass in older individuals would further our knowledge of mechanisms related to managing molecular damage that may be targeted to preserve physical resilience. To characterize expression patterns of genes responsible for the oxidative stress response, RNA was extracted and sequenced from skeletal muscle biopsies collected from 575 participants (≥70 years old) from the Study of Muscle, Mobility, and Aging. Expression levels of 21 protein-coding RNAs related to the oxidative stress response were analyzed in relation to six phenotypic measures, including maximal mitochondrial respiration from muscle biopsies (Max OXPHOS), physical performance (VO2 peak, 400-m walking speed, and leg strength), and muscle size (thigh muscle volume and whole-body D3Cr muscle mass). The mRNA level of the oxidative stress response genes most consistently associated across outcomes are preferentially expressed within the mitochondria. Higher expression of mRNAs that encode generally mitochondria located proteins SOD2, TRX2, PRX3, PRX5, and GRX2 were associated with higher levels of mitochondrial respiration and VO2 peak. In addition, greater SOD2, PRX3, and GRX2 expression was associated with higher physical performance and muscle size. Identifying specific mechanisms associated with high functioning across multiple performance and physical domains may lead to targeted antioxidant interventions with greater impacts on mobility and independence.
Subject(s)
Aging , Muscle, Skeletal , Oxidative Stress , Humans , Oxidative Stress/genetics , Aged , Aging/genetics , Aging/metabolism , Male , Muscle, Skeletal/metabolism , Female , Physical Functional Performance , Mitochondria/metabolism , Mitochondria/genetics , Mitochondria, Muscle/metabolism , Mitochondria, Muscle/genetics , Aged, 80 and overABSTRACT
Las miopatías metabólicas son trastornos de la producción de energía muscular que provocan una disfunción muscular esquelética. Las miopatías relacionadas con el ejercicio comprenden un grupo de enfermedades musculares (Tabla 1y 2) con sintomatología inducida por el ejercicio muscular o situaciones de demanda energética. Las enfermedades del metabolismo energético muscular son un grupo de enfermedades heterogéneas desde el punto de vista genético, clínico y bioquímico. Esquemáticamente desde el punto de vista bioquímico pueden ser agrupadas en tres categorías, así las podemos subdividir en alteraciones del metabolismo de los hidratos de carbono, trastornos del metabolismo lipídico y alteraciones de la función mitocondrial. La genética es el área donde en los últimos años las aportaciones han sido más relevantes y numerosas, gracias a los avances proporcionados por las técnicas de genética molecular. El conocimiento, localización y clonaje de los distintos genes han facilitado enormemente el avance científico de estas enfermedades (AU)
Metabolic myopathies are disorders of muscle energy production that impair skeletal muscle function. Exercise-related myopathies are a group of muscle diseases in which symptoms a retriggered during muscle exercise or in situation of increased metabolic demands. This group of diseases is heterogeneous from a genetic, clinical and biochemical point of view. From a biochemical perspective, they can be grouped into three categories: alterations in carbohydrate and lipid metabolism, respectively, and alterations in mitochondrial function. The main advances in the understanding of these diseases come mainly from molecular biology techniques (AU)
Subject(s)
Humans , Male , Female , Muscular Diseases/diagnosis , Muscular Diseases/genetics , Muscular Diseases/metabolism , Exercise/physiology , Energy Metabolism/genetics , Energy Metabolism/physiology , Lipid Metabolism Disorders/genetics , Lipid Metabolism Disorders/pathology , Mitochondria, Muscle/genetics , Mitochondria, Muscle/metabolism , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Glycogen Storage Disease Type II/complications , Glycogen Storage Disease Type II/diagnosis , Carnitine/deficiency , Carnitine/metabolismABSTRACT
OBJECTIVE@#To explore depletion of human mitochondrial DNA 4977-bp and its relation with aging.@*METHODS@#Total DNA (nuclear and mtDNA) was extracted from 100mg muscle tissue. UV light illumination of ethidium bromide-stained PCR products was used to study the depletion of mtDNA (wild-type or mutant).@*RESULTS@#The proportions of mtDNA depletion in human skeletal muscle could be determined. The frequency of mtDNA 4977-bp depletion in different age groups (0-9, 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89, 90-99) was: 0%, 0%, 0.003%, 0.011%, 0.015%, 0.033%, 0.038%, 0.062%, 0.069%, and 0.091%, respectively.@*CONCLUSION@#Our findings suggest that the frequency of the mtDNA4977 depletion in human skeletal muscle increases with age. It might be useful for human age estimation.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Age Factors , Aging/genetics , DNA Primers , DNA, Mitochondrial/metabolism , Mitochondria, Muscle/genetics , Muscle, Skeletal/metabolism , Polymerase Chain Reaction , Sequence DeletionABSTRACT
El estudio de las anormalidades del DNA mitocondrial y de su relaicón con trastornos a nivel de la fosforilación oxidativa y cadena de transporte de electrones ha permitido la descripción de una gama de síndromes denominados enfermedades o citopatías mitocondriales. El objetivo del presente trabajo es hacer una revisión de los aspectos clínicos más relevantes de este diverso grupo de enfermedades, y proponer un algoritmo diagnóstico, con la finalidad de que los médicos que atienden a estos pacientes puedan considerarlas dentro del espectro de diagnósticos diferenciales en los casos pertinentes