High-density Surface Electromyography as Biomarker of Muscle Aging

Abstract Sarcopenia is a muscle disease with adverse changes that increase throughout the lifetime but with different chronological scales between individuals. Addressing “early muscle aging” is becoming a critical issue for prevention. Through the CHRONOS study, we demonstrated the ability of the high-density surface electromyography (HD-sEMG), a noninvasive, wireless, portable technology, to detect both healthy muscle aging and accelerated muscle aging related to a sedentary lifestyle, one of the risk factors of sarcopenia. The HD-sEMG signals were analyzed in 91 healthy young, middle-aged, and old subjects (25–75 years) distributed according to their physical activity status (82 active and 9 sedentary; International Physical Activity Questionnaire) and compared with current methods for muscle evaluation, including muscle mass (dual-energy X-ray absorptiometry [DXA], ultrasonography), handgrip strength, and physical performance. The HD-sEMG signals were recorded from the rectus femoris during sit-to-stand trials, and 2 indexes were analyzed: muscular contraction intensity and muscle contraction dynamics. The clinical parameters did not differ significantly across the aging and physical activity levels. Inversely, the HD-sEMG indexes were correlated to age and were different significantly through the age categories of the 82 active subjects. They were significantly different between sedentary subjects aged 45–54 years and active ones at the same age. The HD-sEMG indexes of sedentary subjects were not significantly different from those of older active subjects (≥55 years). The muscle thicknesses evaluated using ultrasonography were significantly different between the 5 age decades but did not show a significant difference with physical activity. The HD-sEMG technique can assess muscle aging and physical inactivity-related “early aging,” outperforming clinical and DXA parameters

High-density Surface Electromyography as Biomarker of Muscle Aging

Abstract Sarcopenia is a muscle disease with adverse changes that increase throughout the lifetime but with different chronological scales between individuals. Addressing “early muscle aging” is becoming a critical issue for prevention. Through the CHRONOS study, we demonstrated the ability of the high-density surface electromyography (HD-sEMG), a noninvasive, wireless, portable technology, to detect both healthy muscle aging and accelerated muscle aging related to a sedentary lifestyle, one of the risk factors of sarcopenia. The HD-sEMG signals were analyzed in 91 healthy young, middle-aged, and old subjects (25–75 years) distributed according to their physical activity status (82 active and 9 sedentary; International Physical Activity Questionnaire) and compared with current methods for muscle evaluation, including muscle mass (dual-energy X-ray absorptiometry [DXA], ultrasonography), handgrip strength, and physical performance. The HD-sEMG signals were recorded from the rectus femoris during sit-to-stand trials, and 2 indexes were analyzed: muscular contraction intensity and muscle contraction dynamics. The clinical parameters did not differ significantly across the aging and physical activity levels. Inversely, the HD-sEMG indexes were correlated to age and were different significantly through the age categories of the 82 active subjects. They were significantly different between sedentary subjects aged 45–54 years and active ones at the same age. The HD-sEMG indexes of sedentary subjects were not significantly different from those of older active subjects (≥55 years). The muscle thicknesses evaluated using ultrasonography were significantly different between the 5 age decades but did not show a significant difference with physical activity. The HD-sEMG technique can assess muscle aging and physical inactivity-related “early aging,” outperforming clinical and DXA parameters

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old