In longevity studies, pulses of high doses are being explored; no established regimen in humans.
In mice, fisetin (a flavonoid from strawberries and other fruits) was the most potent senolytic among several flavonoids: it eliminated senescent cells and extended health and lifespan. The basis of the interest in fisetin for aging; preclinical, with no equivalent clinical proof.
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Fisetin is a flavonoid present in notable concentrations in strawberries and, to a lesser extent, in apples, persimmons, onions, and grapes, which for decades went relatively unnoticed among the thousands of dietary polyphenols until a 2018 paper in EBioMedicine by the group of Paul Robbins and James Kirkland at Mayo Clinic identified it as one of the most potent natural compounds for selectively eliminating the senescent cells that accumulate with age.
Senescent cells are a paradoxical phenomenon in the biology of aging: they are cells that have stopped dividing but remain active, secreting a cocktail of proinflammatory molecules (the SASP, senescence-associated secretory phenotype) that damages neighboring tissues and contributes to most chronic diseases of aging; senolytics are compounds that selectively kill these cells without affecting healthy ones, and fisetin is the natural senolytic with the most robust preclinical data to date.
The study by Yousefzadeh and colleagues compared ten different flavonoids for their ability to eliminate senescent cells in cell cultures and in aged mice: fisetin stood out above all the others, selectively eliminating senescent cells in multiple tissues and, most strikingly, extending the median lifespan of treated mice even when treatment was started late in life, along with improvements in physical function, chronic inflammation, and biological markers of aging.
These preclinical findings generated enthusiasm in the geroprotection community, and several clinical trials in humans are currently under way (including a Mayo Clinic study in postmenopausal women with osteoporosis) using high intermittent doses (typically 20 mg/kg/day for 2 days a month); the final clinical results have not yet been published, but the preliminary data are reasonably promising.
Beyond its senolytic effect, fisetin has documented neuroprotective activity in animal models of Alzheimer's disease, Parkinson's disease, and cerebral ischemia: it facilitates long-term potentiation (the molecular basis of memory), reduces the aggregation of neurotoxic proteins, and modulates several signaling pathways involved in neuronal survival, which has fueled interest in its use as a nootropic, although clinical evidence in humans is still scarce.
As a flavonoid, fisetin has the anti-inflammatory and antioxidant properties typical of the family, with activity on several inflammatory mediators (NF-kB, TNF-alpha, interleukins) and direct antioxidant capacity; these effects are quantitatively modest compared with those of other, better-studied polyphenols such as quercetin or resveratrol, but sufficient to contribute to the general profile of dietary flavonoids.
Fisetin is sold as a supplement in capsules of 100-500 milligrams, and popular "senolytic" protocols follow the preclinical logic of high intermittent doses (1,000-1,500 milligrams daily for 2 days a month), although this regimen is not supported by completed clinical trials in humans and should be considered experimental; ideally with a fatty meal to improve absorption, because oral bioavailability is modest without a lipid matrix.
It is generally well tolerated at the doses studied; adverse effects are rare and mild; drug interactions are not well characterized, but as a flavonoid it may modulate some hepatic cytochrome P450 enzymes at high doses; people taking anticoagulants should exercise theoretical caution because of antiplatelet effects, and caution is advisable in pregnancy, breastfeeding, and bleeding disorders because of limited data; since it is experimental, the most reasonable course is to wait for the ongoing clinical trials to confirm regimens and efficacy before applying senolytic protocols on your own.
Information, not medical advice. Scientific evidence reflects the quality of the studies.