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Fisetin Slows Onset of Degeneration in SAMP8 Accelerated Aging Mice

Fisetin is a candidate senolytic compound, demonstrated to induce apoptosis in senescent cells in a petri dish. Clearance of senescence cells is a path to rejuvenation therapies capable to some degree of turning back aspects of aging: the presence of these cells is harmful, a cause of aging. It is also a supplement, and can be obtained from a few different companies that - at present, at least - all repackage the product of a single bulk supplier. The primary reason why I'm not presently arranging a self-experimentation study of one involving this substance is that there is no demonstration that fisetin is senolytic in mice, rather than in cell cultures. One has to draw the line somewhere, and this seems like a sensible choice - it is entirely possible to see promising results in cells evaporate in live animals.

With that in mind, I found the research linked here to be interesting, even though the researchers make no mention of senescent cells. They demonstrate that fisetin added to the diet of SAMP8 mice holds back some of the accelerated aging suffered by this lineage. Do SAMP8 mice have a high load of senescent cells in comparison to their wild type counterparts, and is this a contributing cause of their accelerated aging? There is surprisingly little consideration of this question in the scientific literature, possibly because these mice are near all used in Alzheimer's disease research, a field that so far has little connection to investigations of cellular senescence. I had to do fair bit of digging to find even one paper in which this was a topic of discussion - and it presents evidence for premature senescence of SAMP8 cells in culture, rather than in live animals. Nonetheless, take a look and see what you think.

"Companies have put fisetin into various health products but there hasn't been enough serious testing of the compound. Based on our ongoing work, we think fisetin might be helpful as a preventative for many age-associated neurodegenerative diseases, not just Alzheimer's disease (AD), and we'd like to encourage more rigorous study of it." Previous research found that fisetin reduced memory loss related to Alzheimer's in mice genetically modified to develop the disease. But that study focused on genetic (familial) AD, which accounts for only 1 to 3 percent 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, researchers 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 team 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, 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 team 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."

Link: https://www.salk.edu/news-release/evidence-shows-natural-plant-compound-may-reduce-mental-effects-aging/

Comments

Two things senolytics seem to have in common:

1 -' Like the other compounds, it has also been shown to be reactive in many different assays of biological activities, raising the possibility that any drug generated from fisetin would have too many side effects to be useful.'

2 -'Likely may have carcinogenic activity or an anti-cancer activity '

Posted by: john hewitt at July 12th, 2017 9:51 AM

@John
Yet another reason why Oisin is ahead of the game with their approach.

Posted by: Anonymoose at July 12th, 2017 11:08 AM

Just looking through the pathways Fisetin inhibits, it seems like a good anti aging drug candidate - it inhibits cytokines which are upregulated in inflamaging.

Posted by: Anonymoose at July 12th, 2017 11:11 AM

@anonymoose
Re: Osin. Maybe. What do mitochondria do when they find out their hostcell has induced Casp9 without their permission?

Posted by: john hewitt at July 12th, 2017 11:25 AM

Initiate apoptosis I imagine.

Posted by: Anonymoose at July 12th, 2017 11:50 AM

@anon In any event, if had to choose a place to first promote iCasp9 it would likely be in the intestinal crypts where CCO1 deficient mitos may have compromised the local stem cell pool as described herein
https://en.wikipedia.org/wiki/Cytochrome_c_oxidase_subunit_I

Posted by: john hewitt at July 12th, 2017 11:58 AM

FWIW, Quercitin has essentially the same structure and natural function as Fisetin,and is a fraction of the price in supplement form. It seems likely to me they would function the same in the human body. Why is it that researchers want to research these two chemicals separately?

Posted by: JohnD at July 12th, 2017 9:13 PM

@JohnD: Similar or not, they have meaningfully different outcomes in animal studies.

Posted by: Reason at July 13th, 2017 7:15 AM

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