Posted on Dec 30, 2018, 5 p.m.
Reducing the burden of damaged senescent cells has been shown in previous studies to extend lifespans, and improve health, even if treatment is initiated late in life. Now the researchers from the Mayo Clinic and University of Minnesota Medical School faculty Laura J. Niedernhofer and Paul D. Robbins have demonstrated aged mice treated with Fisetin to have had positive effects on health and lifespan.
When cells get to a certain level of damage they go through an aging process called senescence, as people age these cells accumulate and release inflammatory factors that tell the immune system to clear them, however with age the immune system isn’t able to clear them as effectively, thus they accumulate and cause low level inflammation releasing enzymes that can degrade tissue.
Fisetin was been found to help reduce the level of these damaged senescent cells within the body, as published in EBioMedicine. Treating mice near the end of their lifespans with Fisetin was observed to significantly improve and extend health and lifespans.
Fisetin is a natural flavonoid compound present in many fruits and vegetables, that no adverse effects have been reported from, even at high doses. According to the team supplementation or intermittent treatment with it could help to improve healthy aging, even among the elderly. Fisetin can be found in apples, grapes, persimmon, strawberries, onions, and cucumbers among others.
Fisetin hasn’t been used like this before due to limitations in figuring out how a drug will act on different tissues and different cells in an aging body, and largely due to scientists not having a way to identify if a treatment was attacking the particular senescent cells until recently.
The team used mass cytometry technology and applied it to aging research under guidance of Professor Edgar Arriaga of the University of Minnesota in a technique unique to their research, in the first demonstration showing the effects of the specific drug on specific subsets of these damaged cells within a given tissue in addition to showing that the drug works.
The same team demonstrated the combination of dasatinib and quercetin to be potent senolytics, showing the cocktail to improve various age related conditions such as frailty, CVD, and osteoporosis in previous studies. Fisetin was compared against other compounds including rutin, luteolin, curcumin, resveratrol, epigallocatechin, apigenin, catechin, myricetin, and pirfenidone.
Aging processes are complex and account for numerous pathways, as well as both genetic and environmental components including: 1) Chronic sterile inflammation; 2) Macromolecular changes in lipids, proteins, carbohydrate, DNA, and mitochondria; 3) Stem cell and progenitor dysfunction; and 4) Increased cellular senescence. Senescent cells for example accumulate with age and at sites of pathogenesis in chronic diseases. Such processes are linked in that interventions that target one appear to attenuate others such as senescent cells accumulating with age and at pathogenesis sites in chronic disease; reduction in burden of senescent cells can lead to decreased inflammation, macromolecular dysfunction, and enhanced function of stem/progenitor cells; adult stem cells also become dysfunctional with age displaying evidence of senescence.
The compound was tested against a panel of other flavonoids and was demonstrated to have had the most potent senotherapeutic effects in several cell types in vitro, as well as showing strong anti-geronic effects in vivo. The compound is natural product commonly found in many foods as well as being available in oral dietary supplements which has had no reported adverse side effects, according to the team.
The team’s preclinical data suggests it should be imminently translatable and could have significant benefit to the health of to elderly populations. Based on their findings clinical trials are underway to evaluate short term benefits of intermittent fisetin treatment on certain aspects of aging such as frailty.
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