Prdx6 Plays a Main Role in the Crosstalk Between Aging and Metabolic Sarcopenia.
Francesca PacificiDavid Della-MorteFrancesca PiermariniRoberto ArrigaMaria Giovanna ScioliBarbara CapuaniDonatella PastoreAndrea CoppolaSilvia ReaGiulia DonadelAikaterini AndreadiPasquale AbeteGiuseppe SconocchiaAlfonso BelliaAugusto OrlandiDavide LauroPublished in: Antioxidants (Basel, Switzerland) (2020)
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-β-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.
Keyphrases
- skeletal muscle
- oxidative stress
- glycemic control
- early stage
- type diabetes
- transcription factor
- community dwelling
- dna damage
- signaling pathway
- insulin resistance
- binding protein
- squamous cell carcinoma
- pi k akt
- cardiovascular disease
- weight loss
- endothelial cells
- stress induced
- molecularly imprinted
- heat stress
- protein protein
- endoplasmic reticulum stress
- induced apoptosis
- lymph node
- wound healing
- neoadjuvant chemotherapy
- tandem mass spectrometry
- liquid chromatography