期刊
ANTIOXIDANTS
卷 9, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/antiox9040329
关键词
aging; insulin resistance; peroxiredoxin6; diabetes mellitus; sarcopenia; SIRT1
资金
- Fondazione Roma [NCDS-2013-00000331]
- Age-Associated Inflammation as a Shared Pathogenic Mechanism and Potential Therapeutic Target
- Fondazione Roma-Diabetes Mellitus, Regenerative and Reparative Processes, and Improvement of Pancreatic Beta Cell Function: Role of Bone Marrow-Mesenchymal Stem Cells, MicroRNAs, M2 Macrophages and Myeloid Derived Suppressor Cells
- Fondazione Umberto Di Mario
- ASI [2013-084-R0]
- COREA Research Project, Italian Space Agency
- Evelyn F. McKnight Brain Institute
- PRIN 2015 [2015373Z39_009]
- PRIN 2017 [201793XZ5A_004]
With the increase in average life expectancy, several individuals are affected by age-associated non-communicable chronic diseases (NCDs). The presence of NCDs, such as type 2 diabetes mellitus (T2DM), leads to the reduction in skeletal muscle mass, a pathological condition defined as sarcopenia. A key factor linking sarcopenia with cellular senescence and diabetes mellitus (DM) is oxidative stress. We previously reported as the absence of Peroxiredoxin 6 (Prdx6), an antioxidant enzyme implicated in maintaining intracellular redox homeostasis, induces an early-stage of T2DM. In the present study we sought to understand the role of Prdx6 in the crosstalk between aging and diabetic sarcopenia, by using Prdx6 knockout (Prdx6(-/-)) mice. Absence of Prdx6 reduced telomeres length and Sirtuin1 (SIRT1) nuclear localization. An increase in Sa-beta-Gal activity and p53-p21 pro-aging pathway were also evident. An impairment in IGF-1 (Insulin-like Groth Factor-1)/Akt-1/mTOR pathway leading to a relative increase in Forkhead Box O1 (FOXO1) nuclear localization and in a decrease of muscle differentiation as per lower levels of myoblast determination protein 1 (MyoD) was observed. Muscle atrophy was also present in Prdx6(-/-) mice by the increase in Muscle RING finger 1 (MuRF1) levels and proteins ubiquitination associated to a reduction in muscle strength. The present study, innovatively, highlights a fundamental role of Prdx6, in the crosstalk between aging, sarcopenia, and DM.
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