Addressing the Main Barrier to Sarcopenia Identification: Utility of Practical Office-Based Bioimpedance Tools Vs. Dual Energy X-ray Absorptiometry (DXA) Body Composition for Identification of Low Muscle Mass in Older Adults.

Background: Sarcopenia is associated with increased morbidity and mortality. Clinically, sarcopenia can be overlooked, especially in obesity. Sarcopenia diagnostic criteria include muscle mass (MM) and function assessments. Muscle function can be readily assessed in a clinic setting (grip strength, chair stand test). However, MM requires dual-energy X-ray absorptiometry (DXA) Body Composition (BC) or other costly tools, not readily available. Methods: Observational cohort pilot study of independently mobile, community dwelling older adults, comparing MM using two office-based, direct-to-consumer bioimpedance (BIA) scales (Ozeri® [manufactured in China] and OMRON® [OMRON HBF-510® Full Body Sensor, Shiokoji Horikawa, Kyoto, Japan] to DXA. The OMRON differs from the Ozeri scale because the OMRON also includes hand sensors. The European Working Group on Sarcopenia in Older People (EWGSOP) DXA or BIA low MM diagnostic cut-offs were used to classify participants as having low or normal MM. Results: Fifty participants: 11 men, 39 women. Forty-two completed DXA. Age 75.8 yrs [67-90]. 81% obese based on body fat cut-offs. With DXA [ASM/height2], 15 had low MM. Using BIA [mmass/height2], 7 with Ozeri, and 27 with OMRON, had low MM. Positive predictive value for low MM versus DXA (as the gold standard) for Ozeri was 73.3% and OMRON was 92.8%. Good correlation between BIA scales and DXA for body fat estimates. Conclusions: OMRON captured all low MM participants identified by DXA plus all on DXA diagnostic borderline. Prevalence of obesity was high. Clinically, sarcopenic obese is the most difficult phenotype, as obesity masks low muscle mass. Low cost, readily available, direct-to-consumer BIA BC scales, especially with hand sensors, provide immediate, reliable information on muscle and fat mass. This can prompt appropriate investigation and/or intervention for sarcopenia or sarcopenic obesity.

Selective mRNA translation during eIF2 phosphorylation induces expression of IBTKα.

Disruption of protein folding in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), a transcriptional and translational control network designed to restore protein homeostasis. Central to the UPR is PKR-like ER kinase (PERK/EIF2AK3) phosphorylation of the α subunit of eIF2 (eIF2α∼P), which represses global translation coincident with preferential translation of mRNAs, such as activating transcription factor 4 (ATF4) and C/EBP-homologous protein (CHOP), that serve to implement UPR transcriptional regulation. In this study, we used sucrose gradient ultracentrifugation and a genome-wide microarray approach to measure changes in mRNA translation during ER stress. Our analysis suggests that translational efficiencies vary over a broad range during ER stress, with the majority of transcripts being either repressed or resistant to eIF2α∼P, whereas a notable cohort of key regulators are subject to preferential translation. From the latter group, we identified the α isoform of inhibitor of Bruton's tyrosine kinase (IBTKα) as being subject to both translational and transcriptional induction during eIF2α∼P in both cell lines and a mouse model of ER stress. Translational regulation of IBTKα mRNA involves stress-induced relief of two inhibitory upstream open reading frames in the 5'-leader of the transcript. Depletion of IBTKα by short hairpin RNA reduced viability of cultured cells coincident with increased caspase 3/7 cleavage, suggesting that IBTKα is a key regulator in determining cell fate during the UPR.

Biomechanical evidence for convergent evolution of the invasive growth process among fungi and oomycete water molds.

Diverse microorganisms traditionally called fungi are recognized as members of two kingdoms: mushroom-forming species and their relatives in the Fungi, and oomycete water molds in the Stramenopila. Phylogenetic analysis suggests that these kingdoms diverged early in the evolution of eukaryotes. The phylogenetic detachment of the fungi and oomycetes is reflected in radical differences in their biochemistry, cell structure, and development. In terms of their biological activities, however, they show great similarity, because both groups form colonies of filamentous hyphae that invade and decompose solid food sources. Here we present biomechanical evidence of the convergent evolution of the invasive growth process in these microorganisms. Using miniature strain gauges to measure the forces exerted by single hyphae, we show that the hyphae of species in both kingdoms exert up to 2 atmospheres of hydrostatic pressure as they extend at their tips. No other eukaryotes have adopted this process for meeting their nutritional needs.