CMS121: Novel Approach to Mitigate Aging-related Obesity and Metabolic Dysfunction | Aging-US



April 5, 2024

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  • Aging-US published this research paper on March 20, 2024, in Volume 16, Issue 6, entitled, “CMS121: a novel approach to mitigate aging-related obesity and metabolic dysfunction" by researchers from the Cellular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA; Neurobiology Research Laboratory, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology (NUST), Islamabad, Pakistan; Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, SC 88040-900, Brazil; The Razavi Newman Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, CA. DOI - Corresponding authors - Pamela Maher - and Alcir L. Dafre - Abstract Background: Modulated by differences in genetic and environmental factors, laboratory mice often show progressive weight gain, eventually leading to obesity and metabolic dyshomeostasis. Since the geroneuroprotector CMS121 has a positive effect on energy metabolism in a mouse model of type 2 diabetes, we investigated the potential of CMS121 to counteract the metabolic changes observed during the ageing process of wild type mice. Methods: Control or CMS121-containing diets were supplied ad libitum for 6 months, and mice were sacrificed at the age of 7 months. Blood, adipose tissue, and liver were analyzed for glucose, lipids, and protein markers of energy metabolism. Results: The CMS121 diet induced a 40% decrease in body weight gain and improved both glucose and lipid indexes. Lower levels of hepatic caspase 1, caspase 3, and NOX4 were observed with CMS121 indicating a lower liver inflammatory status. Adipose tissue from CMS121-treated mice showed increased levels of the transcription factors Nrf1 and TFAM, as well as markers of mitochondrial electron transport complexes, levels of GLUT4 and a higher resting metabolic rate. Metabolomic analysis revealed elevated plasma concentrations of short chain acylcarnitines and butyrate metabolites in mice treated with CMS121. Conclusions: The diminished de novo lipogenesis, which is associated with increased acetyl-CoA, acylcarnitine, and butyrate metabolite levels, could contribute to safeguarding not only the peripheral system but also the aging brain. By mimicking the effects of ketogenic diets, CMS121 holds promise for metabolic diseases such as obesity and diabetes, since these diets are hard to follow over the long term. Sign up for free Altmetric alerts about this article - Subscribe for free publication alerts from Aging - Keywords - aging, obesity, diabetes, geroneuroprotection, metabolic disorders, ketogenic diet About Aging-US Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases. Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). Please visit our website at​​ and connect with us: Facebook - X - Instagram - YouTube - LinkedIn - Pinterest - Spotify - Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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