Mitophagy and Oxidative Stress in Cancer and Aging: Focus on Sirtuins and Nanomaterials

Vernucci, Enza; Tomino, Carlo; Molinari, Francesca; Limongi, Dolores; Aventaggiato, Michele; Sansone, Luigi; Tafani, Marco; Russo, Matteo Antonio

doi:10.1155/2019/6387357

Cited by 38 publications

(33 citation statements)

References 220 publications

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“…On the other hand, decreased mitophagy, together with decreased antioxidant capacity during aging can increased ROS levels in the body. The excess production of ROS in stress condition leading to memory deficits, anxiety-like behavior and increase pro-inflammatory cytokine secretion during aging [57][58][59][60]. Although, the exact underlying mechanism of how the decline in autophagy and a rise in ROS levels during aging can elevate pro-inflammatory cytokine release is far from clear.…”

Section: Aging and Autophagymentioning

confidence: 99%

The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of “inflame-aging”

et al. 2020

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Purpose Novel Coronavirus disease 2019 (COVID-19), is an acute respiratory distress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Strangely, ample evidences have been shown that the severity of COVID-19 infections varies widely from children (asymptomatic), adults (mild infection), as well as elderly adults (deadly critical). It has proven that COVID-19 infection in some elderly critical adults leads to a cytokine storm, which is characterized by severe systemic elevation of several pro-inflammatory cytokines. Then, a cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ failure in aged patients. It is far from clear till now why cytokine storm induces in only COVID-19 elderly patients, and not in young patients. However, it seems that aging is associated with mild elevated levels of local and systemic pro-inflammatory cytokines, which is characterized by "inflamm-aging". It is highly likely that "inflamm-aging" is correlated to increased risk of a cytokine storm in some critical elderly patients with COVID-19 infection. Methods A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed. Results The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of "inflamm-aging", mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection.

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Section: Aging and Autophagymentioning

confidence: 99%

The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of “inflame-aging”

et al. 2020

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“…Activation of sirtuin-3 (SIRT-3) was reported to have a positive impact on the stimulation of mitophagy [62]. Among SIRT3 activators, dihydromyricetin and honokiol were tested in various conditions related to mitochondrial functional impairments.…”

Section: Activators Of Mitophagymentioning

confidence: 99%

The Link between Chronic Stress and Accelerated Aging

et al. 2020

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People exposed to chronic stress age rapidly. The telomeres in their cells of all types shorten faster. Inflammation is another important feature of stress that, along with aging, accounts for the phenomenon of inflammaging. In addition to aging itself, inflammaging can contribute to the development of several pathologies, including atherosclerosis, diabetes, hypertension, and others. Oxidative stress is one of the main mechanisms related to stress. Oxidative stress is caused by the over-production of reactive oxygen species (ROS) that can damage various tissues. The main source of ROS is mitochondria. Being suppressed by mitochondrial mutations, mitophagy can aggravate the situation. In this case, the aging-specific pro-inflammatory changes are amplified. It happens because of the inability of cells to maintain the normal state of mitochondria. Macrophages are the crucial element of the innate immunity associated with the chronic inflammation and, subsequently, with the inflammaging. In this review, we focus on the therapy approaches potentially reducing the deleterious effects of oxidative stress. These include stimulation of mitophagy, activation of mitochondrial uncoupling, induction of the expression of the telomerase catalytic component gene, and use of antioxidants. Any method reducing oxidative stress should improve post-traumatic stress disorder.

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“…During the past decade, sirtuins have emerged as critical regulators of endothelial cell behavior and have been directly linked to tumor angiogenesis through multiple signaling pathways and cross-talks (Figure 1). Lack of long-term therapeutic efficacy of current anti-angiogenic strategies requisite for novel angiogenesis inhibitors targeting sirtuins (157,158). Recent discoveries suggest that employing sirtuin isoform specific modulators is a potent anti-angiogenic strategy.…”

Section: Conclusion: Future Perspectives and Novel Therapeutic Approamentioning

confidence: 99%

Role of Sirtuins in Tumor Angiogenesis

et al. 2020

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Generally, changes in the metabolic status of cells under conditions like hypoxia and accumulation of lactate can be sensed by various sensing mechanisms, leading to modulation of a number of signal transduction pathways and transcription factors. Several of the proangiogenic cytokines like VEGF, FGF, PDGF, TGF-β, Ang-2, ILs, etc. are secreted by cancer cells, under hypoxic microenvironment. These cytokines bind to their receptors on the endothelial cells and activates a number of signaling pathways including Akt/PIP3, Src, p38/MAPK, Smad2/3, etc., which ultimately results in the proliferation and migration of endothelial cells. Transcription factors that are activated in response to the metabolic status of tumors include HIFs, NF-κb, p53, El-2, and FOXO. Many of these transcription factors has been reported to be regulated by a class of histone deacetylase called sirtuins. Sirtuins are NAD + dependent histone deacetylases that play pivotal role in the regulation of tumor cell metabolism, proliferation, migration and angiogenesis. The major function of sirtuins include, deacetylation of histones as well as some non-histone proteins like NF-κB, FOXOs, PPAR , PGC1-α, enzymes like acetyl coenzymeA and structural proteins like α tubulin. In the cell, sirtuins are generally considered as the redox sensors and their activities are dependent on the metabolic status of the cell. Understanding the intricate regulatory mechanisms adopted by sirtuins, is crucial in devising effective therapeutic strategies against angiogenesis, metastasis and tumor progression. Keeping this in mind, the present review focuses on the role of sirtuins in the process of tumor angiogenesis and the regulatory mechanisms employed by them.

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Mitophagy and Oxidative Stress in Cancer and Aging: Focus on Sirtuins and Nanomaterials

Cited by 38 publications

References 220 publications

The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of “inflame-aging”

The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of “inflame-aging”

The Link between Chronic Stress and Accelerated Aging

Role of Sirtuins in Tumor Angiogenesis

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