{"id":773,"date":"2018-10-23T15:15:55","date_gmt":"2018-10-23T15:15:55","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=773"},"modified":"2018-10-23T15:15:55","modified_gmt":"2018-10-23T15:15:55","slug":"fisetin-a-new-senolytic","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2018\/10\/23\/fisetin-a-new-senolytic\/","title":{"rendered":"Fisetin—a new senolytic"},"content":{"rendered":"

Senolytic drugs have been the most promising near-term anti-aging therapy since the ground-breaking paper by van Deursen of Mayo Clinic published in <\/span><\/i>2011<\/span><\/i><\/a>. \u00a0The body accumulates senescent cells as we age, damaged cells that send out signal molecules that in turn modify our biochemistry in a toxic, pro-inflammatory direction. \u00a0Though the number of such cells is small, the damage they do is great. Van Deursen showed that just getting rid of these cells could increase lifespan of mice by ~25%. But he did it with a trick, using genetically engineered mice in which the senescent cells had a built-in self-destruct switch. \u00a0<\/span><\/i><\/p>\n

After that, the race was on to find chemical agents that would do the same thing without the genetically engineered self-destruct. \u00a0They must selectively kill senescent cells, while leaving all other cells unharmed. It\u2019s a tall order, because even a little residual toxicity to normal cells can be quite damaging. \u00a0Before last week, the two best candidates were <\/span><\/i>FOXO4-DRI<\/span><\/i><\/a> and a combination of <\/span><\/i>quercetin with dasatinib<\/span><\/i><\/a>.<\/span><\/i><\/p>\n

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I\u2019ve written in the past (<\/span>here<\/span><\/a> and <\/span>here<\/span><\/a>) that senolytic drugs are our best prospect for a near-term lift on the road to anti-aging medicine. \u00a0<\/span><\/p>\n

Last week, a large research group affiliated with the original May Clinic team published <\/span>findings about fisetin<\/span><\/a>, the latest and greatest candidate for a senolitic pill, another flavenoid, very close in structure to quercetin.\u00a0<\/span><\/p>\n

They grew senescent and normal cells in a test tube, then tested 11 different plant-derived chemicals for power to kill the one while leaving the other unharmed. \u00a0The winner was fisetin. <\/span><\/p>\n

(MEF stands for Mouse Embryonic Fybroblast, the cells that were cultured in the screening experiment.)<\/span><\/p>\n

Fisetin is especially interesting because it is cheap, easily available, widely-regarded as safe, but not nearly as well studied as quercetin.<\/span><\/p>\n

They took the winner, fisetin, and subjected it to a series of tests. \u00a0They began with <\/span>in vitro <\/span><\/i>(cell culture) tests and proceeded to <\/span>in vivo <\/span><\/i>tests with live animals, culminating with an impressive life span assay in mice.<\/span><\/p>\n

(The runner-up was curcumin, less interesting perhaps only because it has already been extensively studied. \u00a0The curcumin molecule is unrelated to quercetin or fisetin, and is not a flavenoid. I can\u2019t help but wonder if they had subjected curcumin to the same thorough testing that they reserved for fisetin, how would curcumin have fared?)<\/span><\/p>\n

curcumin<\/figcaption><\/figure>\n

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The paper\u2019s principal findings were:<\/span><\/p>\n