Abstract
Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the “senescence-associated-secretory-phenotype” (SASP), playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5) and neonatal human dermal (NHDF) fibroblasts were used as cellular model to evaluate the effect of chronic (4–6 weeks) treatment with 1 μM hydroxytyrosol (HT) or 10 μM oleuropein aglycone (OLE) on senescence/inflammation markers. Both phenols were effective in reducing β-galactosidase-positive cell number and p16 protein expression. In addition, senescence/inflammation markers such as IL-6 and metalloprotease secretion, and Ciclooxigenase type 2 (COX-2) and α-smooth-actin levels were reduced by phenol treatments. In NHDF, COX-2 expression, Nuclear Factor κ-light-chain-enhancer of activated B cells (NFκB) protein level and nuclear localization were augmented with culture senescence and decreased by OLE and HT treatment. Furthermore, the inflammatory effect of Tumor Necrosis Factor α (TNFα) exposure was almost completely abolished in OLE- and HT-pre-treated NHDF. Thus, the modulation of the senescence-associated inflammatory phenotype might be an important mechanism underlying the beneficial effects of olive oil phenols.
Highlights
Cellular senescence is characterized by complex modifications in the protein expression profile of the cell, leading to replicative arrest and cell dysfunction [1]
Senescent cells are characterized by a strong increase in the secretion of growth factors, inflammatory cytokines, and proteolytic enzymes, termed the “senescence-associated secretory phenotype” (SASP), that has been thoroughly described in cultured fibroblasts [2]
The SASP is thought to play a major role in many age-related diseases, such as Alzheimer’s disease [3], cancer [4], where it contributes to the maintenance of a chronic inflammation which is typical of this pathology [5], and endothelial dysfunction in cardiovascular diseases and type 2 diabetes, characterized by a low-grade chronic inflammation state [6]
Summary
Cellular senescence is characterized by complex modifications in the protein expression profile of the cell, leading to replicative arrest and cell dysfunction [1]. Twheeekpsa)rtarmeaettmeresnat swseitshseodlivine porhdeenroltsooenvaselunaetsecesnecneesdceevnecleopwmeerne:t tihseshtootwalnninumFibgeurreof2.ceTlhlse cpoalrleacmteedtearsnadssceosusnedtedinaotrdtheer teondevoaflutahtee tsreenaetmsceennct,etwheerpee: rtcheenttoatgael nouf mcebllesr of cells collected and counted at the end of the treatment, the percentage of cells positive to SA-βgal staining, and the level of p16 protein expression Both hydroxytyrosol (HT) and oleuropein aglycone (OLE) brought about a significant increment in cell number, while SA-βgal staining and p16 protein. In a sub-group of experiments we aimed at evaluating the effect of the treatment with OLE and HT on externally-induced inflammation, using a 3 h Tumor Necrosis Factor α (TNFα) stimulation. Sscui.b2-0g17r,o1u8p, 22o7f5experiments we aimed at evaluating the effect of the treatment with OLE6 aofn1d3 HT on externally-induced inflammation, using a 3 h Tumor Necrosis Factor α (TNFα) stimulation iinn hhiigghh PPDDLL ((oolldd)) NNHHDDFF. TfloutoarlesNceFnκcBe finluteonresistcye(nbc)eainndteMnsaintyde(rb’)s caonedffiMcieanntd(eMr’1s)c(oc)e,fufisceiedntto(aMss1e)ss(cN),FuκsBepd6t5ocoalsosceaslsizNatFioκnBwpi6th cthoeloncualcilzeautsio(nDwAiPthI),twheerneudcleetuersm(DinAedPIb),ywmeereandseotefrImmiangeedJ bsoyftmweaarnes. *ofp I
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