scholarly journals Age-Related Maintenance of the Autophagy-Lysosomal System Is Dependent on Skeletal Muscle Type

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Raquel Fernando ◽  
José Pedro Castro ◽  
Tanina Flore ◽  
Stefanie Deubel ◽  
Tilman Grune ◽  
...  

The skeletal muscle plays an important role in maintaining whole-body mechanics, metabolic homeostasis, and interorgan crosstalk. However, during aging, functional and structural changes such as fiber integrity loss and atrophy can occur across different species. A commonly observed hallmark of aged skeletal muscle is the accumulation of oxidatively modified proteins and protein aggregates which point to an imbalance in proteostasis systems such as degradation machineries. Recently, we showed that the ubiquitin-proteasomal system was impaired. Specifically, the proteasomal activity, which was declining in aged M. soleus (SOL) and M. extensor digitorum longus (EDL). Therefore, in order to understand whether another proteolytic system would compensate the decline in proteasomal activity, we aimed to investigate age-related changes in the autophagy-lysosomal system (ALS) in SOL, mostly consisting of slow-twitch fibers, and EDL, mainly composed of fast-twitch fibers, from young (4 months) and old (25 months) C57BL/6JRj mice. Here, we focused on changes in the content of modified proteins and the ALS. Our results show that aged SOL and EDL display high levels of protein modifications, particularly in old SOL. While autophagy machinery appears to be functional, lysosomal activity declines gradually in aged SOL. In contrast, in old EDL, the ALS seems to be affected, demonstrated by an increased level of key autophagy-related proteins, which are known to accumulate when their delivery or degradation is impaired. In fact, lysosomal activity was significantly decreased in old EDL. Results presented herein suggest that the ALS can compensate the high levels of modified proteins in the more oxidative muscle, SOL, while EDL seems to be more prone to ALS age-related alterations.

2013 ◽  
Vol 73 (1) ◽  
pp. 16-33 ◽  
Author(s):  
Ailsa A. Welch

Age-related muscle loss impacts on whole-body metabolism and leads to frailty and sarcopenia, which are risk factors for fractures and mortality. Although nutrients are integral to muscle metabolism the relationship between nutrition and muscle loss has only been extensively investigated for protein and amino acids. The objective of the present paper is to describe other aspects of nutrition and their association with skeletal muscle mass. Mechanisms for muscle loss relate to imbalance in protein turnover with a number of anabolic pathways of which the mechanistic TOR pathway and the IGF-1–Akt–FoxO pathways are the most characterised. In terms of catabolism the ubiquitin proteasome system, apoptosis, autophagy, inflammation, oxidation and insulin resistance are among the major mechanisms proposed. The limited research associating vitamin D, alcohol, dietary acid–base load, dietary fat and anti-oxidant nutrients with age-related muscle loss is described. Vitamin D may be protective for muscle loss; a more alkalinogenic diet and diets higher in the anti-oxidant nutrients vitamin C and vitamin E may also prevent muscle loss. Although present recommendations for prevention of sarcopenia focus on protein, and to some extent on vitamin D, other aspects of the diet including fruits and vegetables should be considered. Clearly, more research into other aspects of nutrition and their role in prevention of muscle loss is required.


2021 ◽  
Author(s):  
Yoshihito Sakai ◽  
Norimitsu Wakao ◽  
Hiroki Matsui ◽  
Tsuyoshi Watanabe ◽  
Hiroki Iida ◽  
...  

Abstract Although the prevalence and the associated burden of LBP increase with age, research on LBP has primarily focused on young people and adults, and little attention has been given to the elderly population. Chronic inflammation is well-known as senescence associated secretory phenotype (SASP), which produces numerous proinflammatory cytokines leading to age-related inflammation. We enrolled 203 patients with an average age of 79.0 years, with non-specific CLBP; the patients were compared with age- and sex-matched controls without CLBP using a propensity score-matched analysis. We performed laboratory analysis, radiographic evaluations for global spinal parameter and lumbar degeneration assessment, and body composition analysis using whole-body dual-energy X-ray absorptiometry. We observed a higher red blood cell distribution width (RDW), as well as a lower skeletal muscle mass index and a higher fat mass in patients with CLBP. Moreover, patients with geriatric CLBP had significantly lower lumbar lordosis, and higher sagittal vertical axis was correlated with lower muscle mass in the extremities and trunk, independent of lumbar degeneration. Geriatric CLBP is associated with senescence. RDW, which is an index of aging, was high among elderly patients with CLBP. Furthermore, geriatric patients with CLBP often have age-related skeletal muscle mass reduction and spinal sagittal malalignment.


1987 ◽  
Vol 63 (1) ◽  
pp. 257-261 ◽  
Author(s):  
G. D. Cartee ◽  
R. P. Farrar

Old rats have a decreased hindlimb muscle respiratory capacity and whole-body maximal O2 consumption (VO2 max). The decline in spontaneous physical activity in old rats might contribute to these age-related changes. The magnitude of the age-related decline is not uniform in all skeletal muscle respiratory enzymes, and the decrease in palmitate oxidation is particularly great. This study was designed to determine if young and old rats subjected to the same exercise-training protocol would attain similar values for VO2 max and several markers of muscle respiratory capacity. Four- and 18-mo-old Fischer 344 rats underwent an identical 6-mo program of treadmill running. After training, both age groups had increased VO2 max above sedentary age-matched controls. However, the old trained rats had a lower VO2 max than identically trained young rats. In contrast to VO2 max, the two trained groups attained similar values for gastrocnemius citrate synthase, cytochrome oxidase, 3-hydroxyacyl-CoA dehydrogenase, palmitate oxidation, and total carnitine concentration. Thus, when the young and old rats performed an identical exercise protocol within the capacity of the old animals, differences in skeletal muscle respiratory capacity were eliminated. The dissimilarity in VO2 max between the identically trained groups was apparently caused by age-related differences in factors other than muscle respiratory capacity.


2001 ◽  
Vol 280 (3) ◽  
pp. C540-C547 ◽  
Author(s):  
Dawn A. Lowe ◽  
Jack T. Surek ◽  
David D. Thomas ◽  
LaDora V. Thompson

We tested the hypothesis that low specific tension (force/cross-sectional area) in skeletal muscle from aged animals results from structural changes in myosin that occur with aging. Permeabilized semimembranosus fibers from young adult and aged rats were spin labeled site specifically at myosin SH1 (Cys-707). Electron paramagnetic resonance (EPR) was then used to resolve and quantify the structural states of the myosin head to determine the fraction of myosin heads in the strong-binding (force generating) structural state during maximal isometric contraction. Fibers from aged rats generated 27 ± 0.8% less specific tension than fibers from younger rats ( P < 0.001). EPR spectral analyses showed that, during contraction, 31.6 ± 2.1% of myosin heads were in the strong-binding structural state in fibers from young adult animals but only 22.1 ± 1.3% of myosin heads in fibers from aged animals were in that state ( P = 0.004). Biochemical assays indicated that the age-related change in myosin structure could be due to protein oxidation, as indicated by a decrease in the number of free cysteine residues. We conclude that myosin structural changes can provide a molecular explanation for age-related decline in skeletal muscle force generation.


2020 ◽  
Vol 21 (3) ◽  
pp. 1010 ◽  
Author(s):  
Clara Crescioli

In the elderly, whole-body health largely relies on healthy skeletal muscle, which controls body stability, locomotion, and metabolic homeostasis. Age-related skeletal muscle structural/functional deterioration is associated with a higher risk of severe comorbid conditions and poorer outcomes, demanding major socioeconomic costs. Thus, the need for efficient so-called geroprotective strategies to improve resilience and ensure a good quality of life in older subjects is urgent. Skeletal muscle senescence and metabolic dysregulation share common cellular/intracellular mechanisms, potentially representing targets for intervention to preserve muscle integrity. Many factors converge in aging, and multifaceted approaches have been proposed as interventions, although they have often been inconclusive. Physical exercise can counteract aging and metabolic deficits, not only in maintaining tissue mass, but also by preserving tissue secretory function. Indeed, skeletal muscle is currently considered a proper secretory organ controlling distant organ functions through immunoactive regulatory small peptides called myokines. This review provides a current perspective on the main biomolecular mechanisms underlying age-dependent and metabolic deterioration of skeletal muscle, herein discussed as a secretory organ, the functional integrity of which largely depends on exercise and myokine release. In particular, muscle-derived interleukin (IL)-6 is discussed as a nutrient-level biosensor. Overall, exercise and vitamin D are addressed as optimal geroprotective strategies in view of their multi-target effects.


2019 ◽  
Vol 117 ◽  
pp. 45-52 ◽  
Author(s):  
Raquel Fernando ◽  
Cathleen Drescher ◽  
Stefanie Deubel ◽  
Tobias Jung ◽  
Mario Ost ◽  
...  

2016 ◽  
Vol 113 (8) ◽  
pp. 2212-2217 ◽  
Author(s):  
João-Paulo G. Camporez ◽  
Max C. Petersen ◽  
Abulizi Abudukadier ◽  
Gabriela V. Moreira ◽  
Michael J. Jurczak ◽  
...  

Sarcopenia, or skeletal muscle atrophy, is a debilitating comorbidity of many physiological and pathophysiological processes, including normal aging. There are no approved therapies for sarcopenia, but the antihypertrophic myokine myostatin is a potential therapeutic target. Here, we show that treatment of young and old mice with an anti-myostatin antibody (ATA 842) for 4 wk increased muscle mass and muscle strength in both groups. Furthermore, ATA 842 treatment also increased insulin-stimulated whole body glucose metabolism in old mice, which could be attributed to increased insulin-stimulated skeletal muscle glucose uptake as measured by a hyperinsulinemic-euglycemic clamp. Taken together, these studies provide support for pharmacological inhibition of myostatin as a potential therapeutic approach for age-related sarcopenia and metabolic disease.


Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 372
Author(s):  
Jason Tallis ◽  
Sharn Shelley ◽  
Hans Degens ◽  
Cameron Hill

Obesity is a global epidemic and coupled with the unprecedented growth of the world’s older adult population, a growing number of individuals are both old and obese. Whilst both ageing and obesity are associated with an increased prevalence of chronic health conditions and a substantial economic burden, evidence suggests that the coincident effects exacerbate negative health outcomes. A significant contributor to such detrimental effects may be the reduction in the contractile performance of skeletal muscle, given that poor muscle function is related to chronic disease, poor quality of life and all-cause mortality. Whilst the effects of ageing and obesity independently on skeletal muscle function have been investigated, the combined effects are yet to be thoroughly explored. Given the importance of skeletal muscle to whole-body health and physical function, the present study sought to provide a review of the literature to: (1) summarise the effect of obesity on the age-induced reduction in skeletal muscle contractile function; (2) understand whether obesity effects on skeletal muscle are similar in young and old muscle; (3) consider the consequences of these changes to whole-body functional performance; (4) outline important future work along with the potential for targeted intervention strategies to mitigate potential detrimental effects.


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