Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging

The cellular basis of age-related tissue deterioration remains largely obscure. The ability to activate compensatory mechanisms in response to environmental stress is an important factor for survival and maintenance of cellular functions. Autophagy is activated both under short and prolonged stress and is required to clear the cell of dysfunctional organelles and altered proteins. We report that specific autophagy inhibition in muscle has a major impact on neuromuscular synaptic function and, consequently, on muscle strength, ultimately affecting the lifespan of animals. Inhibition of autophagy also exacerbates aging phenotypes in muscle, such as mitochondrial dysfunction, oxidative stress, and profound weakness. Mitochondrial dysfunction and oxidative stress directly affect acto-myosin interaction and force generation but show a limited effect on stability of neuromuscular synapses. These results demonstrate that age-related deterioration of synaptic structure and function is exacerbated by defective autophagy

Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging

The cellular basis of age-related tissue deterioration remains largely obscure. The ability to activate compensatory mechanisms in response to environmental stress is an important factor for survival and maintenance of cellular functions. Autophagy is activated both under short and prolonged stress and is required to clear the cell of dysfunctional organelles and altered proteins. We report that specific autophagy inhibition in muscle has a major impact on neuromuscular synaptic function and, consequently, on muscle strength, ultimately affecting the lifespan of animals. Inhibition of autophagy also exacerbates aging phenotypes in muscle, such as mitochondrial dysfunction, oxidative stress, and profound weakness. Mitochondrial dysfunction and oxidative stress directly affect acto-myosin interaction and force generation but show a limited effect on stability of neuromuscular synapses. These results demonstrate that age-related deterioration of synaptic structure and function is exacerbated by defective autophagy

Association of lifestyle factors and inflammation with sarcopenic obesity: data from the PREDIMED-Plus trial

Background Sarcopenia is a progressive age-related skeletal muscle disorder associated with increased likelihood of adverse outcomes. Muscle wasting is often accompanied by an increase in body fat, leading to ‘sarcopenic obesity’. The aim of the present study was to analyse the association of lifestyle variables such as diet, dietary components, physical activity (PA), body composition, and inflammatory markers, with the risk of sarcopenic obesity. Methods A cross-sectional analysis based on baseline data from the PREDIMED-Plus study was performed. A total of 1535 participants (48% women) with overweight/obesity (body mass index: 32.5 ± 3.3 kg/m2; age: 65.2 ± 4.9 years old) and metabolic syndrome were categorized according to sex-specific tertiles (T) of the sarcopenic index (SI) as assessed by dual-energy X-ray absorptiometry scanning. Anthropometrical measurements, biochemical markers, dietary intake, and PA information were collected. Linear regression analyses were carried out to evaluate the association between variables. Results Subjects in the first SI tertile were older, less physically active, showed higher frequency of abdominal obesity and diabetes, and consumed higher saturated fat and less vitamin C than subjects from the other two tertiles (all P < 0.05). Multiple adjusted linear regression models evidenced significant positive associations across tertiles of SI with adherence to the Mediterranean dietary score (P-trend < 0.05), PA (P-trend < 0.0001), and the 30 s chair stand test (P-trend < 0.0001), whereas significant negative associations were found with an inadequate vitamin C consumption (P-trend < 0.05), visceral fat and leucocyte count (all P-trend < 0.0001), and some white cell subtypes (neutrophils and monocytes), neutrophil-to-lymphocyte ratio, and platelet count (all P-trend < 0.05). When models were additionally adjusted by potential mediators (inflammatory markers, diabetes, and waist circumference), no relevant changes were observed, only dietary variables lost significance. Conclusions Diet and PA are important regulatory mediators of systemic inflammation, which is directly involved in the sarcopenic process. A healthy dietary pattern combined with exercise is a promising strategy to limit age-related sarcopenia

Association of lifestyle factors and inflammation with sarcopenic obesity: data from the PREDIMED-Plus trial

Background Sarcopenia is a progressive age-related skeletal muscle disorder associated with increased likelihood of adverse outcomes. Muscle wasting is often accompanied by an increase in body fat, leading to ‘sarcopenic obesity’. The aim of the present study was to analyse the association of lifestyle variables such as diet, dietary components, physical activity (PA), body composition, and inflammatory markers, with the risk of sarcopenic obesity. Methods A cross-sectional analysis based on baseline data from the PREDIMED-Plus study was performed. A total of 1535 participants (48% women) with overweight/obesity (body mass index: 32.5 ± 3.3 kg/m2; age: 65.2 ± 4.9 years old) and metabolic syndrome were categorized according to sex-specific tertiles (T) of the sarcopenic index (SI) as assessed by dual-energy X-ray absorptiometry scanning. Anthropometrical measurements, biochemical markers, dietary intake, and PA information were collected. Linear regression analyses were carried out to evaluate the association between variables. Results Subjects in the first SI tertile were older, less physically active, showed higher frequency of abdominal obesity and diabetes, and consumed higher saturated fat and less vitamin C than subjects from the other two tertiles (all P < 0.05). Multiple adjusted linear regression models evidenced significant positive associations across tertiles of SI with adherence to the Mediterranean dietary score (P-trend < 0.05), PA (P-trend < 0.0001), and the 30 s chair stand test (P-trend < 0.0001), whereas significant negative associations were found with an inadequate vitamin C consumption (P-trend < 0.05), visceral fat and leucocyte count (all P-trend < 0.0001), and some white cell subtypes (neutrophils and monocytes), neutrophil-to-lymphocyte ratio, and platelet count (all P-trend < 0.05). When models were additionally adjusted by potential mediators (inflammatory markers, diabetes, and waist circumference), no relevant changes were observed, only dietary variables lost significance. Conclusions Diet and PA are important regulatory mediators of systemic inflammation, which is directly involved in the sarcopenic process. A healthy dietary pattern combined with exercise is a promising strategy to limit age-related sarcopenia

Mechanisms and aging related diseases

Le vieillissement est une perte progressive et inéluctable des capacités fonctionnelles de l’organisme. Des caractéristiques socio-économiques, des facteurs génétiques et le genre influent sur ce processus et en déterminent la complexité. Les mécanismes moléculaires et cellulaires, qui fondent la physiologie du vieillissement et de la longévité, commencent à être mieux élucidés. Souvent ambivalents, ils sont aussi impliqués dans la survenue de nombreuses pathologies liées à l’âge. Certains d’entre-eux (les principaux) sont décrits dans cet article (restriction calorique, séquences télomériques, klotho, Apolipoprotéine E, voie de signalisation mTOR, axe IGF-1/PI3 kinase/insuline, sirtuines, autophagie, radicaux libres, etc.). Une meilleure compréhension de ces mécanismes suscite beaucoup d’espoirs en termes de prévention et de perspectives thérapeutiques. Néanmoins, des dérives éthiques possibles sont redoutées. Le vieillissement est, ainsi, un enjeu sociétal et de santé publique aussi bien dans les pays développés que dans les pays en développement. Le problème de sa prise en charge se posera avec acuité devant l’augmentation de l’espérance de vie et du nombre de personnes âgées dans le monde.Aging is known as a process leading to a progressive and relentless decline of functional capacities. Social, economic, gender and genetic factors are key modulators of its complexity. A better understanding of cellular and molecular mechanisms that underlie aging and life span physiology is slowly but surely occurring. Here, we give a comprehensive synthesis of the main biological mechanisms controlling aging and aging related diseases (caloric restriction, telomeric sequences, Klotho, Apolipoproteine E, mTOR pathway, IGF-1/PI3 kinase/insulin axis, sirtuins, autophagy, free radicals...). Promising hopes in terms of aging prevention and therapeutic perspectives are made in the near future. Nevertheless, general public fear ethical excesses. At all events, aging is becoming a social and public health stake in developed and developing countries. The elderly care management will be a huge issue regarding the enhancement of life span and the growing number of seniors worldwide