Re: [GRG] Dasatinib + Quercetin eliminate senescent cells

On a somewhat related note – there seems to be yet another reason for quercetin

P71 – Can semi-synthetic flavonoids return old microglia to their youthful state?

Free Radical Biology and Medicine, Volume 75, Supplement 1, October 2014, Page S45

Nataša Mrvová, Marcela Kuniaková, Vladimír Knezl, Miroslav Veverka, Jana Navarová, Radomír Nosál, Lucia Racková

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A number of studies have indicated that brain inflammation may deteriorate during normal aging and that neuroinflammation is amplified in age-related neurodegenerative diseases. A pivotal role in age-related neuroinflammatory pathologies is attributed to amplified and prolonged activation of microglia. In addition, microglia from the aged brain were reported as senescent displaying many functional impairments. Flavonoids were shown to be promising molecules in modulation of neuroinflammation. Quercetin, a naturally occurring flavonoid, was proven to downregulate inflammatory genes in microglia. Synthetically modified quercetin, 3´-O-(3-chloropivaloyl)quercetin (CPQ), is assumed to posses better biological availability and enhanced antioxidant properties. In the present study, the antineuroinflammatory capacity of CPQ was assessed in BV-2 microglial cells and rat primary microglia. CPQ suppressed more efficiently than its precursor quercetin LPS-induced NO production and iNOS protein expression. However, neither of the compounds tested influenced significantly phagocytosis of BV-2 cells. In addition, CPQ showed a somewhat better suppression of PMA-induced generation of superoxide than did quercetin. Unlike quercetin, CPQ caused a decline in BV-2 microglia proliferation (without any impact on cell viability) along with interference with cell cycle progression. Both compounds tested at 10uM concentration notably enhanced viability of microglia-enriched cultures prepared from 22-month-old rat brains. This was followed by suppression of lipofuscin-like autofluorescence, improvement of lysosomal function and protection of mitochondria in the old microglia. These results can highlight the therapeutic potential of CPQ as a novel antiinflammatory drug in neurodegenerative diseases. In addition, our data suggest that both natural and semisynthetic flavonoids might protect functions of old microglia [VEGA2/0031/12,1/0076/13;APVV-0052-10;ITMS26240220040].


About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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