Acarbose has sex-dependent and -independent effects on age-related physical function, cardiac health, and lipid biology
| العنوان: | Acarbose has sex-dependent and -independent effects on age-related physical function, cardiac health, and lipid biology |
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| المؤلفون: | John E. Wilkinson, Oliver Fiehn, Jea H Park, Michael J. MacCoss, Michael Garratt, Kaitlyn Pifer, Sean Louzon, Jonathan J. Herrera, Jeremy Whitson, Kate Szczesniak, Danielle C. Leander, Richard A. Miller, Gennifer E. Merrihew, Sharlene M. Day |
| المصدر: | JCI insight, vol 5, iss 21 JCI Insight JCI Insight, Vol 5, Iss 21 (2020) |
| بيانات النشر: | American Society for Clinical Investigation, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Aging, Disease, Inbred C57BL, Cardiovascular, Lipidoses, Mice, chemistry.chemical_compound, 0302 clinical medicine, skin and connective tissue diseases, Inbred BALB C, Acarbose, media_common, Mice, Inbred BALB C, Mice, Inbred C3H, Liver Disease, Liver Diseases, Age Factors, Heart, General Medicine, Lipidome, Inbred C3H, Physical Conditioning, Heart Disease, 030220 oncology & carcinogenesis, Medicine, Female, Research Article, medicine.drug, Drug, medicine.medical_specialty, media_common.quotation_subject, Cardiomegaly, Biology, Cellular senescence, 03 medical and health sciences, Sex Factors, Physical Conditioning, Animal, Internal medicine, medicine, Animals, Glycoside Hydrolase Inhibitors, Pathological, Triglyceride, Animal, Prevention, Type 2 Diabetes Mellitus, Lipid metabolism, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, chemistry, Digestive Diseases |
| الوصف: | With an expanding aging population burdened with comorbidities, there is considerable interest in treatments that optimize health in later life. Acarbose (ACA), a drug used clinically to treat type 2 diabetes mellitus (T2DM), can extend mouse life span with greater effect in males than in females. Using a genetically heterogeneous mouse model, we tested the ability of ACA to ameliorate functional, pathological, and biochemical changes that occur during aging, and we determined which of the effects of age and drug were sex dependent. In both sexes, ACA prevented age-dependent loss of body mass, in addition to improving balance/coordination on an accelerating rotarod, rotarod endurance, and grip strength test. Age-related cardiac hypertrophy was seen only in male mice, and this male-specific aging effect was attenuated by ACA. ACA-sensitive cardiac changes were associated with reduced activation of cardiac growth–promoting pathways and increased abundance of peroxisomal proteins involved in lipid metabolism. ACA further ameliorated age-associated changes in cardiac lipid species, particularly lysophospholipids — changes that have previously been associated with aging, cardiac dysfunction, and cardiovascular disease in humans. In the liver, ACA had pronounced effects on lipid handling in both sexes, reducing hepatic lipidosis during aging and shifting the liver lipidome in adulthood, particularly favoring reduced triglyceride (TAG) accumulation. Our results demonstrate that ACA, already in clinical use for T2DM, has broad-ranging antiaging effects in multiple tissues, and it may have the potential to increase physical function and alter lipid biology to preserve or improve health at older ages. Acarbose treatment ameliorates age-associated declines in physical function and cardiac structural ageing, changes that are linked to slowed changes in the cardiac lipidome. |
| وصف الملف: | application/pdf |
| تدمد: | 2379-3708 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::617a852dee0348614c33e49520bd0815 https://doi.org/10.1172/jci.insight.137474 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....617a852dee0348614c33e49520bd0815 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23793708 |
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