Mechanisms of aging and potential role of selected polyphenols in extending healthspan

Russo, Gian Luigi; Spagnuolo, Carmela; Russo, Maria; Tedesco, Idolo; Moccia, Stefania; Cervellera, Carmen

doi:10.1016/j.bcp.2019.113719

Cited by 80 publications

(44 citation statements)

References 96 publications

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“…Senotherapies have recently entered clinical trials, and two strategies—the combination of the protein kinase inhibitor Dasatinib with the flavonoid Quercetin (D + Q) and UBX0101, a compound disrupting the interaction between Mdm2 and p53—have shown tolerability and a safe profile. Interestingly, compounds with predicted senolytic or senostatic properties are currently in clinical trials for COVID‐19 (Table 1): quercetin, shown to be senolytic in various preclinical models (Russo et al, 2020), is tested as prophylactic treatment; anakinra, tocilizumab, pirfenidone, and ruxolitinib, all shown to have the capacity to inhibit parts of the SASP (Hubackova et al, 2012; Laberge et al, 2015; Orjalo et al, 2009; Rodier et al, 2009; Soto‐Gamez & Demaria, 2017), are used to treat the hyperinflammatory syndrome associated with severe COVID‐19 disease; sirolimus, an mTOR inhibitor which can reduce SASP and prevent senescence induction (geroconversion) (Blagosklonny et al, 2018; Laberge et al, 2015), is tested as treatment against SARS‐CoV‐2 spread and it is thought to prevent severe progression in COVID‐19 (Omarjee et al, 2020); metformin, an anti‐diabetic drug that activates AMPK and lower NFkB leading to SASP reduction (Moiseeva et al, 2013), is tested as an intervention against the acute respiratory syndrome.…”

Section: Future Outlook: Cellular Senescence As Biomarker and Target mentioning

confidence: 99%

Cellular senescence as a potential mediator of COVID‐19 severity in the elderly

et al. 2020

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Coronavirus disease 2019 (COVID-19) represents a complex respiratory distress syndrome which can evolve into multi-organ failure caused by the betacoronavirus SARS-CoV-2. Epidemiological data shows that COVID-19 has a rising mortality particularly in males with advanced age. In United States, Europe, and China, individuals over 60 years of age with underlying conditions such as hypertension, diabetes, cardiovascular or respiratory disease, and cancer are considered to be more at risk to develop severe symptoms (Chen

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Section: Future Outlook: Cellular Senescence As Biomarker and Target mentioning

confidence: 99%

Cellular senescence as a potential mediator of COVID‐19 severity in the elderly

et al. 2020

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“…Although still speculative, this observation can open the doors to investigate more in deep the possibility that p57 participates in mediating the antiaging effects of polyphenols. The field appears extremely promising since we do believe and commented elsewhere [183] that the molecular mechanisms of the beneficial effects of polyphenols in aging and non-communicable diseases must be approached working on their applications at nutritional (not pharmacological) doses, like those present in polyphenols-enriched diets and/or nutraceuticals/functional foods.…”

Section: Discussionmentioning

confidence: 99%

Regulation of p27Kip1 and p57Kip2 Functions by Natural Polyphenols

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Stampone

Cervellera

et al. 2020

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In numerous instances, the fate of a single cell not only represents its peculiar outcome but also contributes to the overall status of an organism. In turn, cell division cycle and its control strongly influence cell destiny playing a critical role in targeting it towards a specific phenotype. Several factors participate to the control of growth and among them p27 and p57, two proteins modulating various transitions of cell cycle, appear to play key functions. In this review, the major features of p27 and p57 will be described, focusing in particular on their recently identified roles not directly correlated to cell cycle modulation. Then, their possible role as molecular effectors of polyphenols activities are discussed. Polyphenols represent a large family of natural bioactive molecules that have been demonstrated to play promising protective activities against several human diseases. Their use has also been proposed in association with classical therapies for ameliorating their clinical effects and for diminishing their negative side activities. The importance of p27 and p57 in polyphenol cellular effects will be discussed with the aim of identifying novel therapeutic strategies for the treatment of important human diseases, such as cancers, characterized by an altered control of growth.

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“…The biological processes of aging and senescence are accelerated by obesity, linked to metabolic syndrome, and the risk of developing chronic diseases increases with age [ 23 ]. The extension of lifespan and healthspan is dependent on behavioral, pharmacologic, and dietary factors, which remain largely unknown [ 24 ]. However, non-nutrient dietary antioxidants such as flavonoids are considered potential anti-aging agents or lifespan essentials.…”

Section: The Relevance Of Flavonoids In Obesity Preventionmentioning

confidence: 99%