The world population is ageing rapidly. As society ages, the incidence of physical limitations is dramatically increasing, which reduces the quality of life and increases healthcare expenditures. In western society, ~30% of the population over 55 years is confronted with moderate or severe physical limitations. These physical limitations increase the risk of falls, institutionalization, co-morbidity, and premature death. An important cause of physical limitations is the age-related loss of skeletal muscle mass, also referred to as sarcopenia. Emerging evidence, however, clearly shows that the decline in skeletal muscle mass is not the sole contributor to the decline in physical performance. For instance, the loss of muscle strength is also a strong contributor to reduced physical performance in the elderly. In addition, there is ample data to suggest that motor coordination, excitation-contraction coupling, skeletal integrity, and other factors related to the nervous, muscular, and skeletal systems are critically important for physical performance in the elderly. To better understand the loss of skeletal muscle performance with ageing, we aim to provide a broad overview on the underlying mechanisms associated with elderly skeletal muscle performance. We start with a system level discussion and continue with a discussion on the influence of lifestyle, biological, and psychosocial factors on elderly skeletal muscle performance. Developing a broad understanding of the many factors affecting elderly skeletal muscle performance has major implications for scientists, clinicians, and health professionals who are developing therapeutic interventions aiming to enhance muscle function and/or prevent mobility and physical limitations and, as such, support healthy ageing.
The transition to a biobased economy necessitates utilizing renewable resources as a sustainable alternative to traditional fossil fuels. Bioconversion is a way to produce many green chemicals from renewables, e.g., biopolymers like PHAs. However, fermentation and bioconversion processes mostly rely on expensive, and highly refined pure substrates. The utilization of crude fractions from biorefineries, especially herbaceous lignocellulosic feedstocks, could significantly reduce costs. This presentation shows the microbial production of PHA from such a crude stream by a wild-type thermophilic bacterium Schlegelella thermodepolymerans [1]. Specifically, it uses crude xylose-rich fractions derived from a newly developed biorefinery process for grassy biomasses (the ALACEN process). This new stepwise mild flow-through biorefinery approach for grassy lignocellulosic biomass allows the production of various fractions: a fraction containing esterified aromatics, a monomeric xylose-rich stream, a glucose fraction, and a native-like lignin residue [2]. The crude xylose-rich fraction was free of fermentation-inhibiting compounds meaning that the bacterium S.thermodepolymerans could effectively use it for the production of one type of PHA, polyhydroxybutyrate. Almost 90% of the xylose in the refined wheat straw fraction was metabolized with simultaneous production of PHA, matching 90% of the PHA production per gram of sugars, comparable to PHA yields from commercially available xylose. In addition to xylose, S. thermodepolymerans converted oligosaccharides with a xylose backbone (xylans) into fermentable xylose, and subsequently utilized the xylose as a source for PHA production. Since the xylose-rich hydrolysates from the ALACEN process also contain some oligomeric xylose and minor hemicellulose-derived sugars, optimal valorization of the C5-fractions derived from the refinery process can be obtained using S. thermodepolymerans. This opens the way for further exploration of PHA production from C5-fractions out of a variety of herbaceous lignocellulosic biomasses using the ALACEN process combined with S. thermodepolymerans. Overall, the innovative utilization of renewable resources in fermentation technology, as shown herein, makes a solid contribution to the transition to a biobased economy.[1] W. Zhou, D.I. Colpa, H. Permentier, R.A. Offringa, L. Rohrbach, G.J.W. Euverink, J. Krooneman. Insight into polyhydroxyalkanoate (PHA) production from xylose and extracellular PHA degradation by a thermophilic Schlegelella thermodepolymerans. Resources, Conservation and Recycling 194 (2023) 107006, ISSN 0921-3449, https://doi.org/10.1016/j.resconrec.2023.107006. [2] S. Bertran-Llorens, W.Zhou. M.A.Palazzo, D.I.Colpa, G.J.W.Euverink, J.Krooneman, P.J.Deuss. ALACEN: a holistic herbaceous biomass fractionation process attaining a xylose-rich stream for direct microbial conversion to bioplastics. Submitted 2023.
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AimsGenetic hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere protein-encoding genes (i.e. genotype-positive HCM). In an increasing number of patients, HCM occurs in the absence of a mutation (i.e. genotype-negative HCM). Mitochondrial dysfunction is thought to be a key driver of pathological remodelling in HCM. Reports of mitochondrial respiratory function and specific disease-modifying treatment options in patients with HCM are scarce.Methods and resultsRespirometry was performed on septal myectomy tissue from patients with HCM (n = 59) to evaluate oxidative phosphorylation and fatty acid oxidation. Mitochondrial dysfunction was most notably reflected by impaired NADH-linked respiration. In genotype-negative patients, but not genotype-positive patients, NADH-linked respiration was markedly depressed in patients with an indexed septal thickness ≥10 compared with <10. Mitochondrial dysfunction was not explained by reduced abundance or fragmentation of mitochondria, as evaluated by transmission electron microscopy. Rather, improper organization of mitochondria relative to myofibrils (expressed as a percentage of disorganized mitochondria) was strongly associated with mitochondrial dysfunction. Pre-incubation with the cardiolipin-stabilizing drug elamipretide and raising mitochondrial NAD+ levels both boosted NADH-linked respiration.ConclusionMitochondrial dysfunction is explained by cardiomyocyte architecture disruption and is linked to septal hypertrophy in genotype-negative HCM. Despite severe myocardial remodelling mitochondria were responsive to treatments aimed at restoring respiratory function, eliciting the mitochondria as a drug target to prevent and ameliorate cardiac disease in HCM. Mitochondria-targeting therapy may particularly benefit genotype-negative patients with HCM, given the tight link between mitochondrial impairment and septal thickening in this subpopulation.
