Towards healthy aging : the effect of senolytics on age-related diseases

Cellular senescence is a state of cell cycle arrest that takes place in response to damaging stimuli such as telomere shortening. Despite their short-term beneficial effects, senescent cells have been proven to accumulate during aging, contributing to a wide range of age-related pathologies. Because of this, senolysis, a novel therapeutic approach based on senescence-targeted clearance, has rapidly emerged as a treatment candidate to achieve healthy-aging. This poster focuses on the recently discovered senolytic drug combination dasatinib plus quercetin, which has shown protective effects in a plethora of aging phenotypes such as neurological, metabolic, cardiovascular, endocrine or physical conditions associated with old age. Whether senolytics will become the Holy Grail of aging is still to be seen, but they are sure to bring geroscience to an exciting point in which important progress on the study of aging will be made

Resveratrol activates antioxidant protective mechanisms in cellular models of Alzheimer’s disease inflammation

Resveratrol is a natural phenolic compound with known benefits against neurodegeneration. We analyzed in vitro the protective mechanisms of resveratrol against the proinflammatory monomeric C-reactive protein (mCRP). mCRP increases the risk of AD after stroke and we previously demonstrated that intracerebral mCRP induces AD-like dementia in mice. Here, we used BV2 microglia treated with mCRP for 24 h in the presence or absence of resveratrol. Cells and conditioned media were collected for analysis. Lipopolysaccharide (LPS) has also been implicated in AD progression and so LPS was used as a resveratrol-sensitive reference agent. mCRP at the concentration of 50 µg/mL activated the nitric oxide pathway and the NLRP3 inflammasome pathway. Furthermore, mCRP induced cyclooxygenase-2 and the release of proinflammatory cytokines. Resveratrol effectively inhibited these changes and increased the expression of the antioxidant enzyme genes Cat and Sod2. As central mechanisms of defense, resveratrol activated the hub genes Sirt1 and Nfe2l2 and inhibited the nuclear translocation of the signal transducer NF-ĸB. Proinflammatory changes induced by mCRP in primary mixed glial cultures were also protected by resveratrol. This work provides a mechanistic insight into the protective benefits of resveratrol in preventing the risk of AD induced by proinflammatory agents