Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities.

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.

Sarcopenia.

Sarcopenia, the loss of muscle mass and function with age, is highly relevant to clinical practice as it has been associated with a wide range of ageing outcomes including disability and shorter survival times. As such it is now a major focus for research and drug discovery. There has been recent progress in the development of consensus definitions for the diagnosis of sarcopenia, taking the form of measurements of muscle mass and strength or physical performance. These definitions form potential inclusion criteria for use in trials, although the optimum choice of outcome measures is less clear. Prevalence estimates using these new definitions vary, although they suggest that sarcopenia is a common (approximately 13% from one study) clinical problem in older people. A range of lifestyle factors have been investigated in regard to the development of this condition, and progressive resistance training is the most well-established intervention so far. There is also marked research interest in the role of diet, although so far the value of supplementation is less clear. Other potential treatments for sarcopenia include the angiotensin-converting enzyme inhibitors, with some evidence that they can improve physical performance in older people. Future research directions include an increased understanding of the molecular and cellular mechanisms of sarcopenia and the use of a life course approach to explore the possibility of earlier intervention and prevention.

Sarcopenia / Sarcopenia

Sarcopenia, the loss of muscle mass and function with age, is highly relevant to clinical practice as it has been associated with a wide range of ageing outcomes including disability and shorter survival times. As such it is now a major focus for research and drug discovery. There has been recent progress in the development of consensus definitions for the diagnosis of sarcopenia, taking the form of measurements of muscle mass and strength or physical performance. These definitions form potential inclusion criteria for use in trials, although the optimum choice of outcome measures is less clear. Prevalence estimates using these new definitions vary, although they suggest that sarcopenia is a common (approximately 13% from one study) clinical problem in older people. A range of lifestyle factors have been investigated in regard to the development of this condition, and progressive resistance training is the most well-established intervention so far. There is also marked research interest in the role of diet, although so far the value of supplementation is less clear. Other potential treatments for sarcopenia include the angiotensin-converting enzyme inhibitors, with some evidence that they can improve physical performance in older people. Future research directions include an increased understanding of the molecular and cellular mechanisms of sarcopenia and the use of a life course approach to explore the possibility of earlier intervention and prevention.

A sarcopenia, definida como a perda de função e massa muscular que ocorrem com a idade, é altamente relevante para a prática clínica, pois está associada a vários desfechos negativos, incluindo diminuição da funcionalidade e da sobrevida. Houve recente progresso no desenvolvimento de definições para o diagnóstico da sarcopenia, e estas atualmente se compõem tanto de medidas de massa e força muscular quanto do desempenho físico. Essas definições são potencialmente úteis como critérios de inclusão em pesquisas científicas, todavia a escolha de desfechos é menos clara. As estimativas de prevalência utilizando essas novas definições variam, mas elas sugerem que a sarcopenia é um problema clínico comum (cerca de 13% a partir de um estudo) em pessoas idosas. Uma série de fatores de estilo de vida foi investigada em relação ao desenvolvimento dessa condição, e o treinamento de resistência progressiva é a intervenção mais bem estabelecida até o momento. A intervenção dietética também foi aventada como um fator modificável, embora menos clara que a anterior. Outros tratamentos potenciais para sarcopenia incluem os inibidores da enzima conversora de angiotensina, com alguma evidência de que eles podem melhorar o desempenho físico em idosos. Pesquisas futuras que abordem uma maior compreensão dos mecanismos moleculares e celulares da sarcopenia, além de abordagens precoces que possam vir a modificar o surgimento da sarcopenia, são necessárias.