Hydroxytyrosol Interference with Inflammaging via Modulation of Inflammation and Autophagy

Abstract

Inflammaging refers to a chronic, systemic, low-grade inflammation, driven by immune (mainly macrophages) and non-immune cells stimulated by endogenous/self, misplaced or altered molecules, belonging to physiological aging. This age-related inflammatory status is characterized by increased inflammation and decreased macroautophagy/autophagy (a degradation process that removes unnecessary or dysfunctional cell components). Inflammaging predisposes to age-related diseases, including obesity, type-2 diabetes, cancer, cardiovascular and neurodegenerative disorders, as well as vulnerability to infectious diseases and vaccine failure, representing thus a major target for anti-aging strategies. Phenolic compounds—found in extra-virgin olive oil (EVOO)—are well known for their beneficial effect on longevity. Among them, hydroxytyrosol (HTyr) appears to greatly contribute to healthy aging by its documented potent antioxidant activity. In addition, HTyr can modulate inflammation and autophagy, thus possibly counteracting and reducing inflammaging. In this review, we reference the literature on pure HTyr as a modulatory agent of inflammation and autophagy, in order to highlight its possible interference with inflammaging. This HTyr-mediated activity might contribute to healthy aging and delay the development or progression of diseases related to aging.

Polyphenol-Rich Extracts from Agroindustrial Waste and Byproducts: Results and Perspectives According to the Green Chemistry and Circular Economy

“…Nevertheless, the bioavailability of major olive polyphenols, standing on their hydrophilic nature, could be improved through structural modification (see section ) and/or encapsulation. Liposomes or biobased nanovesicles represent a practical solution to facilitate the absorption and delivery of phenols and polyphenolic extracts, enabling them to exert their antioxidant and anti-inflammatory properties more efficiently. , In vivo studies have demonstrated that polyphenols-enriched formulations mitigate inflammatory response by inhibiting the production of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and enzymes (p38MAPK) . Additionally, in vitro and in vivo studies revealed that purified HTyr is able to counteract the increase in multiple inflammatory mediators, thereby modulating inflammation and autophagy. , Administration of pure HTyr to human and murine cell lines effectively modulates inflammatory biomarkers (THP-1, PBMC, MRC-5, and RAW 264.7).…”

“…Additionally, in vitro and in vivo studies revealed that purified HTyr is able to counteract the increase in multiple inflammatory mediators, thereby modulating inflammation and autophagy. , Administration of pure HTyr to human and murine cell lines effectively modulates inflammatory biomarkers (THP-1, PBMC, MRC-5, and RAW 264.7). HTyr downregulates the expression of the innate immune receptor TLR-4 and pro-inflammatory cytokines, chemokines, and acute phase proteins . Furthermore, the anti-inflammatory effects of HTyr have been validated in vivo by using animal models of inflammatory diseases. − HTyr can also exert anti-inflammatory activity by modulating the quali-quantitative composition of guttle microbiota. , Among olive phenolic compounds, oleocanthal has been found to exhibit anti-inflammatory activity, inhibiting key enzymes involved in the inflammatory process through mechanisms similar to nonsteroidal anti-inflammatory drugs. , …”

“…HTyr downregulates the expression of the innate immune receptor TLR-4 and pro-inflammatory cytokines, chemokines, and acute phase proteins. 74 Furthermore, the anti-inflammatory effects of HTyr have been validated in vivo by using animal models of inflammatory diseases. 77−79 HTyr can also exert anti-inflammatory activity by modulating the quali-quantitative composition of guttle microbiota.…”

“…72,73 In vivo studies have demonstrated that polyphenols-enriched formulations mitigate inflammatory response by inhibiting the production of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and enzymes (p38MAPK). 74 Additionally, in vitro and in vivo studies revealed that purified HTyr is able to counteract the increase in multiple inflammatory mediators, thereby modulating inflammation and autophagy. 75,76 Administration of pure HTyr to human and murine cell lines effectively modulates inflammatory biomarkers (THP-1, PBMC, MRC-5, and RAW 264.7).…”

Anti-Inflammatory Effects of Olive Leaf Extract and Its Bioactive Compounds Oleacin and Oleuropein-Aglycone on Senescent Endothelial and Small Airway Epithelial Cells

“…Polyphenols have long been studied as antioxidant and anti-inflammatory agents; in the last decade, their efficacy has been demonstrated in the reduction of inflammaging. [ 24 , 25 , 26 ]. Inflammaging is a subclinical systemic inflammation observed during the aging process.…”