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Therefore, it is crucially important to understand the mechanisms by which antiretroviral drugs may contribute to aging. The aim of this study was to investigate the hypothesis that antiretroviral drugs cause increased reactive oxygen species (ROS) generation that results in mitochondrial dysfunction and culminates in promoting cellular senescence. In addition, we applied targeted nanoparticle (NP)-based delivery to specifically enrich mitochondria with coenzyme Q10 (CoQ10) in order to enhance antioxidant protection. The studies employed neural progenitor cells (NPCs), as differentiation of these cells into mature neurons is affected both during HIV infection and in the aging process. Exposure of cultured NPCs to various combinations of HIV antiretroviral therapy (ART) induced a more than 2-fold increase in mitochondrial ROS generation and mitochondrial membrane potential, a more than 50% decrease in oxygen consumption and ATP levels, a 60% decrease in SIRT3 expression, and a 42% decrease in cell proliferation relative to control levels. These alterations were accompanied by a 37% increase in beta-galactosidase staining and a shortening of the telomere length to more than half of the length of controls as assessed by quantitative telomere-FISH labeling, indicating accelerated NPC senescence in response to ART exposure. Importantly, CoQ10 delivered by targeted nanoparticles effectively attenuated these effects. Overall, these results indicate that ART promotes cellular senescence by causing mitochondrial dysfunction, which can be successfully reversed by supplementation with mitochondria-targeted CoQ10.<\/jats:p>","DOI":"10.1021\/acs.molpharmaceut.8b01014","type":"journal-article","created":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T11:02:52Z","timestamp":1545994972000},"page":"724-736","source":"Crossref","is-referenced-by-count":48,"title":["Targeted Mitochondrial COQ10 Delivery Attenuates\nAntiretroviral-Drug-Induced Senescence of Neural Progenitor Cells"],"prefix":"10.1021","volume":"16","author":[{"given":"Martina","family":"Velichkovska","sequence":"first","affiliation":[{"name":"University of Miami Miller School of Medicine , , , ,","place":["Miami, Florida, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bapurao","family":"Surnar","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine , , , ,","place":["Miami, Florida, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhavan","family":"Nair","sequence":"additional","affiliation":[{"name":"Florida International University , , , ,","place":["Miami, Florida, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3042-5272","authenticated-orcid":true,"given":"Shanta","family":"Dhar","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine , , , ,","place":["Miami, Florida, United States"]},{"name":"University of Miami Miller School of Medicine , , , ,","place":["Miami, Florida, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4475-2119","authenticated-orcid":true,"given":"Michal","family":"Toborek","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine , , , ,","place":["Miami, Florida, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2018,12,28]]},"reference":[{"key":"2026090308180165000_cit1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.2147\/HIV.S39665","article-title":"Cognitive impairment\nin patients with AIDS \u2013\nprevalence and severity","volume":"7","author":"Watkins","year":"2015","journal-title":"HIV\/AIDS"},{"key":"2026090308180165000_cit2","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1212\/01.wnl.0000225183.74521.72","article-title":"Antiretroviral\ntherapy improves cognitive impairment in HIV+ individuals in sub-saharan\nAfrica","volume":"67","author":"Sacktor","year":"2006","journal-title":"Neurology"},{"key":"2026090308180165000_cit3","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1093\/cid\/cir627","article-title":"Premature age-related\ncomorbidities among HIV-infected\npersons compared with the general population","volume":"53","author":"Guaraldi","year":"2011","journal-title":"Clin. 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