scholarly journals Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Anastasiya Börsch ◽  
Daniel J. Ham ◽  
Nitish Mittal ◽  
Lionel A. Tintignac ◽  
Eugenia Migliavacca ◽  
...  

AbstractSarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.

2015 ◽  
Vol 25 (4) ◽  
pp. 249 ◽  
Author(s):  
Jan Cvecka ◽  
Veronika Tirpakova ◽  
Milan Sedliak ◽  
Helmut Kern ◽  
Winfried Mayr ◽  
...  

Aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions. One of the most efficient methods to counteract age-related changes in muscle mass and function is physical exercise. An alternative effective intervention to improve muscle structure and performance is electrical stimulation. In the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared.


2021 ◽  
Vol 118 (30) ◽  
pp. e2102344118
Author(s):  
Hao Wang ◽  
Jonathan L. Robinson ◽  
Pinar Kocabas ◽  
Johan Gustafsson ◽  
Mihail Anton ◽  
...  

Genome-scale metabolic models (GEMs) are used extensively for analysis of mechanisms underlying human diseases and metabolic malfunctions. However, the lack of comprehensive and high-quality GEMs for model organisms restricts translational utilization of omics data accumulating from the use of various disease models. Here we present a unified platform of GEMs that covers five major model animals, including Mouse1 (Mus musculus), Rat1 (Rattus norvegicus), Zebrafish1 (Danio rerio), Fruitfly1 (Drosophila melanogaster), and Worm1 (Caenorhabditis elegans). These GEMs represent the most comprehensive coverage of the metabolic network by considering both orthology-based pathways and species-specific reactions. All GEMs can be interactively queried via the accompanying web portal Metabolic Atlas. Specifically, through integrative analysis of Mouse1 with RNA-sequencing data from brain tissues of transgenic mice we identified a coordinated up-regulation of lysosomal GM2 ganglioside and peptide degradation pathways which appears to be a signature metabolic alteration in Alzheimer’s disease (AD) mouse models with a phenotype of amyloid precursor protein overexpression. This metabolic shift was further validated with proteomics data from transgenic mice and cerebrospinal fluid samples from human patients. The elevated lysosomal enzymes thus hold potential to be used as a biomarker for early diagnosis of AD. Taken together, we foresee that this evolving open-source platform will serve as an important resource to facilitate the development of systems medicines and translational biomedical applications.


2018 ◽  
pp. 1-3
Author(s):  
B.C. Clark

Sarcopenia was originally conceptualized as the age-related loss of skeletal muscle mass. Over the ensuing decades, the conceptual definition of sarcopenia has changed to represent a condition in older adults that is characterized by declining muscle mass and function, with “function” most commonly conceived as muscle weakness and/or impaired physical performance (e.g., slow gait speed). Findings over the past 15-years, however, have demonstrated that changes in grip and leg extensor strength are not primarily due to muscle atrophy per se, and that to a large extent, are reflective of declines in the integrity of the nervous system. This article briefly summarizes findings relating to the complex neuromuscular mechanisms that contribute to reductions in muscle function associated with advancing age, and the implications of these findings on the development of effective therapies.


2020 ◽  
Vol 4 ◽  
pp. 81-85
Author(s):  
Maria Borja-Gonzalez ◽  
Jose C. Casas-Martinez ◽  
Brian McDonagh ◽  
Katarzyna Goljanek-Whysall
Keyword(s):  

2012 ◽  
Vol 53 ◽  
pp. S261
Author(s):  
A. McArdle⁎ ◽  
A. Kayani ◽  
A. Vasilaki ◽  
G. Sakellariou ◽  
M. Jackson
Keyword(s):  

2007 ◽  
Vol 293 (3) ◽  
pp. H1721-H1728 ◽  
Author(s):  
Karla Lehle ◽  
Leoni A. Kunz-Schughart ◽  
Peter Kuhn ◽  
Stephan Schreml ◽  
Dietrich E. Birnbaum ◽  
...  

The aim of our study was to evaluate the relevance of tissue- and species-specific endothelial cells (EC) to study EC-dependent mechanisms in inflammatory-mediated tissue injury. We established an isolation protocol for highly purified EC (pEC) preparations of different origin and compared EC-specific inflammatory responses. Fluorescence-activated cell separation was used to obtain pEC cultures from different human arterial (coronary artery, internal thoracic artery) and venous (umbilical vein, saphenous vein) vessels. All pEC were analyzed for growth kinetics, morphology, release of cytokines/chemokines, and expression of E-selectin. For all different EC cultures, purities of ≥99% were reproducibly achieved. The EC isolation did not affect EC growth, morphology, and function. However, characterization of pEC from different vessel materials revealed an intrinsic, tissue-specific functional heterogeneity of EC cultures. Despite an arterial and venous difference in the secretion of IL-8 and monocyte chemoattractant protein-1, especially EC from coronary arteries produced significantly more IL-6 compared with other EC types, independent of age, gender, and disease of the cell donors. In contrast, the expression of E-selectin was not affected. We conclude that the proposed isolation protocol allows the generation of a pEC bank, enabling us to study tissue-specific aspects at the level of the endothelium.


2016 ◽  
pp. 1-10
Author(s):  
C.H. MURPHY ◽  
S.Y. OIKAWA ◽  
S.M. PHILLIPS

It is well accepted that daily protein intake is an important dietary consideration to limit and treat age-related declines in muscle mass, strength, and function. Furthermore, we propose that there is a growing appreciation for the need to consider protein intake on a per-meal basis rather than simply focusing on the total daily protein intake. The existence of a saturable dose-response relationship between muscle protein synthesis (MPS) and the quantity of protein consumed in a single meal/bolus provides the rationale for promoting an even/balanced pattern of daily protein intake. We hypothesize that a balanced/even protein intake pattern with the ingestion a quantity of protein shown to optimally stimulate MPS at each meal may be an effective strategy to alleviate sarcopenic muscle loss. In this review we examine the available evidence supporting the influence of dietary protein intake pattern on muscle protein turnover, muscle mass, and muscle function. We present several practical considerations that, it is proposed, should be taken into account when translating a per-meal protein recommendation into dietary advice for older adults.


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