Researchers at the Salk Institute for Biological Studies have found further evidence that fisetin, a natural flavonoid found in strawberries and other edible fruits or vegetables, reduces cognitive deficits and inflammation associated with aging in mice.
Currais et al find benefits of fisetin in a mouse model of premature aging, Alzheimer’s disease. Image credit: Carl Stridsberg.
The research, led by Dr. Pamela Maher, a senior staff scientist in the Cellular Neurobiology Laboratory at the Salk Institute, was published online in the Journals of Gerontology Series A on June 2, 2017.
The work builds on the team’s previous research into fisetin (3,3’,4’,7-tetrahydroxyflavone), finding it could help treat age-related mental decline and conditions like Alzheimer’s disease (AD) or stroke.
“Companies have put fisetin into various health products but there hasn’t been enough serious testing of the compound,” Dr. Maher said.
“Based on our ongoing work, we think fisetin might be helpful as a preventative for many age-associated neurodegenerative diseases, not just AD, and we’d like to encourage more rigorous study of it.”
Previous research by the team found that fisetin reduced memory loss related to AD in mice genetically modified to develop the disease.
But that study focused on genetic (familial) AD, which accounts for only 1 to 3% of cases.
By far the bigger risk factor for developing what is termed sporadic AD, as well as other neurodegenerative disorders, is simply age.
For the current inquiry, Dr. Maher and co-authors turned to a strain of laboratory mice that age prematurely to better study sporadic AD.
By 10 months of age, these mice typically show signs of physical and cognitive decline not seen in normal mice until two years of age.
The researchers fed the 3-month-old prematurely aging mice a daily dose of fisetin with their food for 7 months. Another group of the prematurely aging mice was fed the same food without fisetin.
During the study period, mice took various activity and memory tests.
The team also examined levels of specific proteins in the mice related to brain function, responses to stress and inflammation.
“At 10 months, the differences between these two groups were striking,” Dr. Maher said.
“Mice not treated with fisetin had difficulties with all the cognitive tests as well as elevated markers of stress and inflammation. Brain cells called astrocytes and microglia, which are normally anti-inflammatory, were now driving rampant inflammation.”
“Mice treated with fisetin, on the other hand, were not noticeably different in behavior, cognitive ability or inflammatory markers at 10 months than a group of untreated 3-month-old mice with the same condition.”
Additionally, the authors found no evidence of acute toxicity in the fisetin-treated mice, even at high doses of the compound.
“Mice are not people, of course, but there are enough similarities that we think fisetin warrants a closer look, not only for potentially treating sporadic AD but also for reducing some of the cognitive effects associated with aging, generally,” Dr. Maher said.
Next, the scientists hope to partner with another group or company in order to conduct clinical trials of fisetin with human subjects.
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Antonio Currais et al. Fisetin Reduces the Impact of Aging on Behavior and Physiology in the Rapidly Aging SAMP8 Mouse. J Gerontol A, published online June 2, 2017; doi: 10.1093/gerona/glx104
