Erik Marchant, a third year PhD student, has published his first paper from his dissertation. Erik used low-frequency ultrasound in old mice with insulin resistance and diabetes and discovered many interesting transcriptomic changes in skeletal muscle that reduce inflammation and alter immune cell function. Erik is a PhD student in the lab of Blake Rasmussen, PhD at the Sam and Ann Barshop Institute for Longevity and Aging Studies.
Low-frequency ultrasound reverses insulin resistance and diabetes-induced changes in the muscle transcriptome in aged mice
Erik D Marchant, Ekta Singh, Sanjay Kureel, Brandon Blair, Hanna Kalenta, Zachary D Von Ruff, Korri S Weldon, Zhao Lai, Michael P Sheetz, Blake B Rasmussen
Am J Physiol Endocrinol Metab. 2025 Jun 1;328(6):E899-E910. doi: 10.1152/ajpendo.00470.2024. Epub 2025 May 5.
Abstract:
The risk for developing insulin resistance and type II diabetes increases with age. Although lifestyle factors contribute to age-related insulin resistance, aging itself independently reduces insulin sensitivity, partially via an increase in inflammation and cellular senescence. Low-frequency ultrasound (LFU) has been shown to rejuvenate senescent cells and to reduce the proinflammatory senescence-associated secretory phenotype. Because diabetes is more common in aged individuals, there is an increased need to develop effective therapeutics for aged individuals with this condition. This study investigated the effects of LFU treatment on muscle function, blood glucose control, and skeletal muscle gene expression in aged, insulin-resistant, and diabetic mice. Insulin resistance was induced via a high-fat, high-sucrose (HFHS) diet, and diabetes was induced via an HFHS diet plus a low dose of streptozotocin. Insulin-resistant and diabetic mice exhibited impaired glucose metabolism and physical function, as well as an altered transcriptomic profile in skeletal muscle, indicating an increase in inflammation and an immune response. LFU treatment reversed much of the transcriptomic changes that occurred with insulin resistance and diabetes but had no effect on blood glucose control or physical function. LFU demonstrates potential as a noninvasive therapy for reducing inflammation and altering immune cell function in skeletal muscle in insulin-resistant and diabetic populations. NEW & NOTEWORTHY This study introduces low-frequency ultrasound (LFU) as a novel, noninvasive therapy that attenuates insulin resistance- and diabetes-induced transcriptional changes in aged skeletal muscle. LFU primarily reduced inflammatory and immune-related gene expression, potentially by promoting a shift toward an anti-inflammatory (M2) macrophage profile. These findings suggest that LFU may target underlying inflammatory mechanisms of insulin resistance and diabetes in aging muscle.
Keywords: RNA-seq; aging; insulin resistance; low-frequency ultrasound; mitochondria.