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.

中文翻译：

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认知脆弱的分子机制：氧-臭氧治疗的潜在治疗靶点。

在过去的十年中，认知脆弱性得到了科学界的极大关注。它的特点是高度炎症和氧化状态、内分泌和代谢改变、线粒体功能障碍以及再生过程和免疫系统减慢，具有复杂和多因素的病因。尽管有几种治疗方法可用，但关于疗效和成本的挑战仍然存在。在这里，我们通过激活几种分子机制（Nrf2-ARE、NF- κB、NFAT、AP-1、HIFα）。我们强调了这些特定过程如何与认知虚弱有关，以确定其治疗的推定治疗靶点。氧-臭氧 (O2-O3) 疗法从未针对认知衰弱进行过测试。因此，这项工作提供了广泛的科学背景，为首次测试这种疗法提供了一致的理论基础，该疗法可以调节认知虚弱受损的免疫、炎症、氧化、代谢、内分泌、微生物群和再生过程。虽然需要洞察力，但 O2-O3 疗法可以代表一种更快、更容易、更便宜的单域干预，在没有对认知脆弱的副作用的情况下起作用。