Senescent cells – cells that have stopped dividing – accumulate with age and accelerate the aging process. Researchers have identified new therapeutic agents that alleviate symptoms of frailty, improving cardiac function and extending a healthy lifespan. Y. Zhu, from Mayo Clinic (Minnesota, USA), and colleagues then developed senolytics – a new class of drugs that in animal models dramatically slows the aging process. First, the researchers had to identify and target senescent cells without damaging other cells. Using transcript analysis, the researchers found that senescent cells have increased expression of “pro-survival networks” that help them resist apoptosis or programmed cell death. The team then identified the cancer drug dasatinib; and quercetin, a natural compound with anti-inflammatory effects, as able to selectively induce death of senescent cells. The investigators then looked at how these drugs affected health and aging in mice. In old mice, cardiovascular function was improved within five days of a single dose of the combined compounds. A single dose led to improved exercise capacity in animals weakened by radiation therapy used for cancer. The effect lasted for at least seven months following treatment. Periodic drug administration of mice with accelerated aging extended the healthspan in the animals, delaying age-related symptoms, spine degeneration and osteoporosis. The study authors submit that: “These results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.”
“Healthy Lifespan” Drugs on the Horizon
Zhu Y, Tchkonia T, Pirtskhalava T, Gower A, Ding H, Giorgadze N, Palmer AK, Ikeno Y, Borden G, Lenburg M, O'Hara SP, LaRusso NF, Miller JD, Roos CM, Verzosa GC, LeBrasseur NK, Wren JD, Farr JN, Khosla S, Stout MB, McGowan SJ, Fuhrmann-Stroissnigg H, Gurkar AU, Zhao J, Colangelo D, Dorronsoro A, Ling YY, Barghouthy AS, Navarro DC, Sano T, Robbins PD, Niedernhofer LJ, Kirkland JL. “The Achilles' Heel of Senescent Cells: From Transcriptome to Senolytic Drugs.” Aging Cell. 2015 Mar 9.
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