Fight Aging!

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/