Molecular mechanisms in cognitive frailty: potential therapeutic targets for oxygen-ozone treatment: Mechanisms of Ageing and Development

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In the last decade, cognitive frailty has gained great attention from the scientific community. It is characterized by high inflammation and oxidant state, endocrine and metabolic alterations, mitochondria dysfunctions and slowdown in regenerative processes and immune system, with a complex and multifactorial aetiology. Although several treatments are available, challenges regarding the efficacy and the costs persist. Here, we proposed an alternative non-pharmacological, non-side-effect, low cost therapy based on anti-inflammation, antioxidant, regenerative and anti-pathogens properties of ozone, through the activation of several molecular mechanisms (Nrf2-ARE, NF-κB, NFAT, AP-1, HIFα). We highlighted how these specific processes could be implicated in cognitive frailty to identify putative therapeutic targets for its treatment. The oxigen-ozone (O2-O3) therapy has never been tested for cognitive frailty. This work provides thus wide scientific background to build a consistent rationale for testing for the first time this therapy, that could modulate the immune, inflammatory, oxidant, metabolic, endocrine, microbiota and regenerative processes impaired in cognitive frailty. Although insights are needed, the O2-O3 therapy could represent a faster, easier, inexpensive monodomain intervention working in absence of side effects for cognitive frailty. © 2020 The Authors
Original languageEnglish
Article number111210
JournalMech. Ageing Dev.
Publication statusPublished - 2020


  • Cognitive frailty
  • Gut microbiota
  • Inflammation
  • Oxidative stress
  • Oxygen-ozone therapy
  • Trace elements
  • cytokine
  • hypoxia inducible factor 1alpha
  • immunoglobulin enhancer binding protein
  • transcription factor AP 1
  • transcription factor NFAT
  • transcription factor Nrf2
  • aging
  • apoptosis
  • cognitive defect
  • cognitive frailty
  • disorders of mitochondrial functions
  • DNA damage
  • epigenetics
  • frailty
  • human
  • immunoregulation
  • inflammation
  • intestine flora
  • metabolic disorder
  • nonhuman
  • oxidative stress
  • oxygen consumption
  • oxygen therapy
  • ozone therapy
  • pathophysiology
  • priority journal
  • regeneration
  • Review
  • risk factor
  • stem cell
  • vasodilatation


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