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Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment., (© 2024. The Author(s).)

Aim: Mitochondrial dysfunction during aging is a key factor that contributes to sarcopenia. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been increasingly recognized to regulate mitochondrial function. The present study aimed to investigate the role of Nrf2 in the development of frailty and sarcopenia during aging, and to demonstrate whether Nrf2 contributes to the maintenance of muscle mass and function by regulation of mitochondrial biogenesis and dynamics during the aging process., Methods: Young (5-6 months), middle-aged (11-13 months), old (20-24 months) Nrf2-/- (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice were used in this study. Physical function of the mice in the 6 groups was assessed by grip strength test, four paw inverted hanging test, rotarod analysis, open field analysis, and treadmill endurance test. Muscle mass was measured by cross-sectional area (CSA) of tibialis anterior muscles and gastrocnemius muscle weight. The frailty status of the 25 old WT mice and 23 old KO mice were assessed based on the mouse frailty phenotype assessment. Expression levels of genes involved in mitochondrial biogenesis (nuclear respiratory factor 1 (Nrf1), peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM)) and mitochondrial dynamics (optic atrophy protein 1 (Opa1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and dynamin-related protein 1 (Drp1)) were measured in the skeletal muscle. SDH staining was performed and mitochondrial DNA (mtDNA) copy number was measured. Transmission electron microscopy was used to measure the mitochondria number and morphology., Results: Physical function and muscle mass decreased during aging. The mRNA expression levels of Nrf2 decreased with increasing frailty phenotype scores in the old WT mice. There were minimal differences in the physical function and muscle mass between the WT and KO mice in the young groups, whereas Nrf2 deficiency caused a declined physical function and muscle mass in the middle-aged and old mice, and exacerbated frailty in the old mice. The decreases of the physical function and muscle mass were accompanied by the reduced expression levels of genes involved in mitochondrial biogenesis and dynamics, as well as a reduction of mitochondrial number, mitochondrial content, mtDNA copy number, and an impaired mitochondria morphology in the skeletal muscle., Conclusion: Nrf2 deficiency exacerbated frailty and sarcopenia during aging, at least partially by impairing skeletal muscle mitochondrial biogenesis and dynamics in an age-dependent manner., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Glaucoma is a leading cause of blindness. Primary open-angle glaucoma, the most common form of glaucoma, is known to increase in prevalence with age. One of its major risk factors is an elevated intraocular pressure believed to be related to the trabecular meshwork (TM), a specialized tissue located at the chamber angle of the eye. Myocilin, a gene linked to open-angle glaucomas (OAG), has been found to be expressed in the TM and a broad range of other ocular and non-ocular tissues. The purpose of this study was to examine the distribution of myocilin protein and mRNA in the TM of normal human eyes to determine whether age-related changes exist. Studies with glaucomatous eyes were carried out concurrently. Immunoperoxidase staining experiments demonstrated positive immunoreactivity for myocilin protein in both the cells and beams in all regions of the TM. The staining intensity and the myocilin level as determined by dot blot assays were not correlated with the ages of donors ranging from 8 weeks to 93 years. Neither did myocilin mRNA, detected by in situ hybridization in cells throughout the TM and quantified by relative quantitative RT-PCR, vary with age. Myocilin mRNA and protein expression in diseased tissues was either comparable to that of normal tissues or reduced. This study represents the first in-depth investigation of myocilin expression in relation to age in the TM of human eyes. The results indicate an age independence, argue thus against a direct role of myocilin and reiterate the involvement of additional factors in the pathogenesis of glaucoma.

[Display omitted] • TP can improve the spatial memory by increasing glucose transport and metabolism. • EGCG has a protective effect on cellular energy metabolism monitored by Seahorse. Tea polyphenols (TP) are the main active components of tea. In our study, the effect of TP on the menopause and aging related memory decline and the mechanisms focused on the brain glucose metabolism were clarified. In vivo, ovariectomy (OVX) combined with D-galactose (D-gal) injection were used to establish the memory decline model. TP administration improved the spatial memory by increasing the expressions of GLUT1, 3 and Tau protein O-GlcNAc glycosylation, decreasing Tau hyper-phosphorylation and the Aβ 1-42 level, and improving the morphology of mitochondria in hippocampus. Furthermore, in vitro, PC12 cells were treated with Aβ 1-42 and EGCG treatment regulated the mitochondrial respiratory function and glycolytic functions, improved the activities of the key enzymes in glycolysis and tricarboxylic acid cycle, increased the SOD activity and decreased the MDA levels in cells. Our study suggests that TP improve the memory in aging ovariectomized rats by regulating brain glucose metabolism. [ABSTRACT FROM AUTHOR]

Tea is a rich source of pharmacologically active molecules that has been suggested to provide a variety of health benefits. However, its mechanism of action in aging-related intestinal flora dysbiosis mediated neuroinflammation is still unclear. This study aimed to explore whether tea polyphenols (TP) can improve memory by regulating intestinal flora mediated neuroinflammation in aging model rats. Ovariectomy (OVX) combined with D-galactose injection was used to establish aging rats related to menopause. The rats were divided into Sham control group, Aging model group, TP 75 mg/kg, 150 mg/kg, 300 mg/kg groups and VE group. After 12 weeks of intervention, the shuttle box test and Y maze test were used to check the memory of rats. The composition of intestinal flora was assessed by 16S rRNA sequencing technology. HE staining and ELISA were used to detect intestinal epithelial morphology and permeability, respectively. TLR4/NF-κB inflammation pathway related indicators were investigated by western blot, and the microglia activation in rat hippocampal tissue was checked by immunofluorescence. In the shuttle box test and the Y maze test, compared with the Sham control group, the memory of Aging model rats was significantly declined. It was observed that the intestinal flora of Aging model rats was dysbiosis, the permeability of the intestinal epithelium was increased. Further experimental results showed that the expression of TLR4/NF-κB inflammatory pathway related proteins in the hippocampus were increased, and the excessive activation of microglia was observed. The beneficial effects of TP intervention have been found to prevent memory decline and significantly improve brain inflammation induced by intestinal flora dysbiosis, and TP 300 mg/kg showed a more obvious advantage than TP 75 mg/kg. TP 300 mg/kg can significantly improve the behavior of rats, improve the composition and diversity of the intestinal flora, and the shape and function of the intestinal epithelium. By reversing the increased expression levels of TLR4, IRAK, p-IκBα and nuclear NF-κB p65 proteins in the hippocampus of Aging model rats, the activation of microglia in the CA1, CA3 and Dentate gyrus (DG) sub-regions of the hippocampus can be inhibited. TP inhibits the brain TLR4/NF-κB inflammatory signal pathway caused by the dysbiosis of intestinal flora, which may be one of the mechanisms to improve the memory decline in aging model rats. [Display omitted] • In this study, ovariectomy and D-galactose injection were used to establish aging model rats related to menopause. • The composition of the intestinal flora of aging rats was dysbiosis, which in turn triggered inflammation in the brain. • This study can provide laboratory evidence for the prevention of menopause-related memory decline. [ABSTRACT FROM AUTHOR]

Sarcopenia is a progressive systemic skeletal muscle disorder characterized by a pathological decline in muscle strength, quantity, and quality, which frequently affects the elderly population. The majority of cancer patients are of advanced age. Patients may already have sarcopenia prior to cancer development, and those with cancer are prone to developing sarcopenia due to hypercatabolism, inflammation, reduced physical fitness, anorexia, adverse effects, and stress associated with anticancer therapy. Based on the timing, sarcopenia in patients with cancer can be categorized into three: pre-existing sarcopenia before the onset of cancer, sarcopenia related to cancer, and sarcopenia related to cancer treatment. Sarcopenia not only changes the body composition of patients with cancer but also increases the incidence of postoperative complications, reduces therapeutic efficacy, impairs quality of life, and results in shortened survival. Different therapeutic strategies are required to match the cancer status and physical condition of patients with different etiologies and stages of sarcopenia. Here, we present a comprehensive review of the epidemiology and diagnosis of sarcopenia in patients with cancer, elucidate the complex interactions between cancer and sarcopenia, and provide evidence-based strategies for sarcopenia management in these patients. [Display omitted] • Cancer and sarcopenia mutually exacerbate, forming a vicious cycle. • Interventions vary depending on temporal occurrence of sarcopenia in cancer. • Early recognition and multimodal interventions are needed for sarcopenia in cancer. [ABSTRACT FROM AUTHOR]