Prdx6 plays a main role in the crosstalk between aging and metabolic sarcopenia

Francesca Pacifici, David Della-Morte, Francesca Piermarini, Roberto Arriga, Maria Giovanna Scioli, Barbara Capuani, Donatella Pastore, Andrea Coppola, Silvia Rea, Giulia Donadel, Aikaterini Andreadi, Pasquale Abete, Giuseppe Sconocchia, Alfonso Bellia, Augusto Orlandi, Davide Lauro

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number329
JournalAntioxidants
Volume9
Issue number4
DOIs
StatePublished - Apr 2020

Keywords

  • Aging
  • Diabetes mellitus
  • Insulin resistance
  • Peroxiredoxin6
  • SIRT1
  • Sarcopenia

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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