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A senolytic (from the words senescence and -lytic, "destroying") is among a class of small molecules under basic research to determine if they can selectively induce death of senescent cells and improve health in humans. [1] A goal of this research is to discover or develop agents to delay, prevent, alleviate, or reverse age-related diseases.
In animal studies, navitoclax was found to be a senolytic agent, inducing apoptosis in senescent, but not non-senescent cells. [4] Oral administration of ABT263 to either sublethally irradiated or normally aged mice reduced senescent cells, including senescent bone marrow hematopoietic stem cells and senescent muscle stem cells.
Senotherapeutics include emerging senolytic/senoptotic small molecules that specifically induce cell death in senescent cells [2] and agents that inhibit the pro-inflammatory senescent secretome. [3] Senescent cells can be targeted for immune clearance, but an ageing immune system likely impairs senescent cell clearance leading to their ...
A senolytic (from the words senescence and -lytic, "destroying") is among a class of small molecules under basic research to determine if they can selectively induce death of senescent cells and improve health in humans. [100] A goal of this research is to discover or develop agents to delay, prevent, alleviate, or reverse age-related diseases.
Niedernhofer studied from 1981 to 1985 at Duke University graduating with a B.S. chemistry, from 1989 to 1990 at Georgetown University School of Medicine graduating with an M.S. in physiology, and from 1990 to 1992 at the University of Alabama at Birmingham with training in medicine.
First developed as a potential cancer chemotherapy, [1] it was subsequently identified as a senolytic (a drug that selectively induces cell death in senescent cells). [2] The Bcl-2 family is most notable for their regulation of apoptosis, a form of programmed cell death, at the mitochondrion; Bcl-2 and Bcl-xL are anti-apoptotic proteins.
Chimeric antigen receptor T cells have been proposed as an alternative means to senolytic drugs for the elimination of senescent cells. [64] Urokinase receptors have been found to be highly expressed on senescent cells, leading researchers to use chimeric antigen receptor T cells to eliminate senescent cells in mice.
[3] [4] Soluble urokinase plasminogen activator surface receptor is part of SASP, and has been used to identify senescent cells for senolytic therapy. [5] Initially, SASP is immunosuppressive (characterized by TGF-β1 and TGF-β3) and profibrotic, but progresses to become proinflammatory (characterized by IL-1β, IL-6 and IL-8) and fibrolytic.
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