New research has revealed that fisetin – a natural flavonoid found in many fruits and vegetables – functions as an effective senolytic agent by clearing out damaged aging cells, improving health and extending lifespan.
When our cells lose the ability to effectively divide and replicate, they generally die and are cleared out by our immune system. But, as we age our immune system becomes less efficient at clearing out these stagnant damaged cells. Called senescent cells, many anti-aging researchers hypothesize the build-up of these cells as fundamental to the development of many chronic age-related diseases.
A great deal of work is currently underway to develop effective senolytic drugs, compounds designed to help clear the body of these senescent cells with the hope of reducing a variety of symptoms we generally associate with aging. Earlier this year a team of researchers revealed a combination of two existing drugs were found to effectively reduce the number of senescent cells in mouse experiments, and extend the animal's lifespan.
The same team has now published a new paper expanding on the previous work, and homing in on better, more potent, senolytic agents. The new research tested ten different flavonoid compounds and discovered fisetin displayed the most potent senotherapeutic effects in both mouse and human tissue experiments.
This isn't the first time fisetin has been implicated in beneficial anti-aging effects. A 2014 study in mice engineered to develop Alzheimer's disease suggested the compound prevented progression of memory loss and learning difficulties. At the time, researchers could only hypothesize exactly how fisetin could be preventing the degenerative characteristics of Alzheimer's since it unexpectedly seemed to have no effect on the build-up of amyloid plaques, thought to be the primary cause of the disease.
It is only recently that researchers have started to investigate associations between neurodegenerative disease and the build-up of senescent cells. Just last month a breakthrough study from a team at the Mayo Clinic suggested evidence of a causal link between cellular senescence in the brain and the symptoms of neurodegenerative disease. This new discovery adds to the growing hypothesis that targeting senescent cells in the brain may be an effective strategy in battling dementia.
One of the key innovations in this new research is the utilization of a technology called mass cytometry to directly observe how a given compound functions within an individual cell. This technology, used here for the first time in aging research, allowed the scientists to closely observe whether a tested treatment was effectively targeting specific senescent cells.
"In addition to showing that the drug works, this is the first demonstration that shows the effects of the drug on specific subsets of these damaged cells within a given tissue," says Paul Robbins, one of the researchers on the project.
As well as its ability to function as a potent senolytic agent, the study examined the effects of fisetin on both health and lifespan, particularly when administered at a late stage to elderly mice. The treatment did successfully reduce a variety of age-related pathological biomarkers as well as extend the median lifespan of the animals.
It is important to note that this research is still only in its nascent stages, and currently only verified in mice models. As many scientists can attest, the leap from animal tests to human verification can often be very large. However, the natural origins of fisetin and its significant track record of safety in humans suggest the research should be able to rapidly move into human clinical trials offering further clarity on whether this treatment will offer anti-aging effects in elderly subjects.
"These results suggest that we can extend the period of health, termed healthspan, even towards the end of life," says Robbins. "But there are still many questions to address, including the right dosage, for example."
The new study was published in the journal EBioMedicine.
Source: University of Minnesota
