The Supplement Industry is a Corrosive Presence, Lacking in Integrity
Senolytic therapies selectively destroy senescent cells, an important cause of inflammation and tissue dysfunction in older individuals. Removal of senescent cells via pharmacological means produces impressive demonstrations of rejuvenation in old mice, reversing the progression of many different age-related conditions. An intermittent or one-time high dose of fisetin has been tested as a senolytic in mice, and showed surprisingly good results. Why surprising? Because the similar compound quercetin does not appear to be meaningfully senolytic on its own. Quercetin improves the ability of the senolytic dasatinib to kill senescent cells; the combination of dasatinib and quercetin was the first pharmacological approach to senolytics tested in mice. The surprise is that fisetin on its own does just as well as dasatinib and quercetin at destroying senescent cells in mice, if the one study showing that outcome is to be taken at face value.
Fisetin is not a widely used supplement, relatively speaking, but it has been used for a good number of years, at doses 30-fold lower than the senolytic dose. What are the odds that an ability to produce sizable gains in human health in late life via an existing supplement was overlooked because a much higher dose was needed? We can debate the possible answers to that question, but it is better to wait for the results of an ongoing clinical trial of fisetin at these higher doses. One might also take a look at the Forever Healthy Foundation report that summarizes what is known of fisetin as a senolytic.
The supplement industry, of course, never waits on clinical trials. It is also an industry well practiced in the matter of lying by omission, distorting scientific findings, and selling hope and fraud rather than factual data. As might be expected given that history, one can presently find any number of groups selling "senolytic" supplements bearing small amounts of fisetin. Similarly for quercetin.
I'm going to point out Elysium Health as a particularly egregious example of this sort of thing, as it was founded by noted scientists in the aging research field, and continues to be associated with the Mayo Clinic, an institution presently carrying out clinical trials of senolytic therapies. If one looks at the latest marketing effort from Elysium that capitalizes on the efforts of researchers, in order to extract money from the credulous and the hopeful, you will find that they do not even say how much fisetin is included in their new product. They tout its link to clinical trials while deliberately obscuring the information needed to validate that the protocol offered is the same. Everyone involved in Elysium Health and its relationship with the research community should be ashamed of themselves.
This is a pointed example of the way in which the supplement industry is corrosive of integrity. I am all in favor of more of the safe senolytics being made more accessible to more people, with guidance on how to follow existing clinical trial programs. Even in advance of confirming human data, if a part of the supplement rollout is to produce equivalent data from a population of supplement users. The formal trial process is too slow, and good data can be obtained at less cost and more rapidly via other means. But there is a right way and a wrong way to go about this, and supplement industry companies near always choose the wrong way. This latest Elysium product adds little, and obscures much.
Elysium Health Announces the Launch of FORMAT Advanced Immune Support
Elysium Health, a leading life sciences company developing clinically validated health products based on advancements in aging research, today announced the launch of FORMAT, the first and only immune product to uniquely pair a daily immunomodulatory supplement with an intermittent senolytic complex to combat the effects of immune aging and provide complete immune support. The Senolytic Complex contains a powerful blend of quercetin and fisetin to help the body manage senescent cells, which supports healthy immune function and combats immunosenescence.
We now have access to substances called senolytics that, when administered on an intermittent basis, help to clear these problematic cells, supporting healthy immune function and helping the body respond to immunosenescence. Format incorporates micronutrients - necessary for baseline immune function - and pairs them with powerful senolytic compounds to keep your immune system functioning optimally. The formulation of Format's Senolytic Complex is based on research led by James Kirkland, M.D., Ph.D., Elysium Scientific Advisory Board member and director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic. This research has shown that senolytics are effective when administered intermittently.
... and Elysium Health pays a lot of 'high calibre' researchers to make it look like they actually are working members of their advisory board.
https://www.elysiumhealth.com/pages/advisory-board
... and among them Jim Kirkland... the same who is the PI of the Mayo Clinic fisetin trials.
And while his trials didn't move a bit in the last 3 years (except for his fisetin cures covid ones), Elysium Health peddles fisetin senolytics to the masses. One could have the impression the trials don't move, because the outcome would destroy Elysium Health's fisetin business. But that would mean that the trial results aren't going to be fake.
And while it's known by now that sirtuin upregulation in long lived mammals does next to nothing anti-aging wise... they still answer the question 'Why are sirtuins important for aging?' like:
'Sirtuins are a family of proteins that regulate cellular health. Sirtuins play a key role in regulating cellular homeostasis. Homeostasis involves keeping the cell in balance. However, sirtuins can only function in the presence of NAD+, nicotinamide adenine dinucleotide, a coenzyme found in all living cells.'
Lying by omission, distorting scientific findings, and selling hope and fraud rather than factual data. Very well put, Reason.
Just this titbit for the commenters who tend to post here that David Sinclair has no financial interest in selling NAD + supplements:
https://www.huffpost.com/entry/david-sinclair-aging-harvard-resveratrol_b_5c61ee61e4b038faea137fb9
'Elysium, co-founded in 2014 by a prominent MIT scientist to commercialize the molecule nicotinamide riboside, a type of NAD booster, highlights its "exclusive" licensing agreement with Harvard and the Mayo Clinic and Sinclair's role as an inventor. According to the company's press release, the agreement is aimed at supplements that slow "aging and age-related diseases."
His (Sinclair) financial interests include being listed as an inventor on a patent licensed to Elysium Health, a supplement company that sells a NAD booster in pills for $60 a bottle.'
This is a very good read w.r.t. senolytics.
Read it while having in mind 'scientists' already sell 'therapies' on popular sites (i.e. Elysium Health).
https://www.nature.com/articles/s41587-020-00750-1
'That means a single senolytic strategy is unlikely to work for all age-related conditions, says Nir Barzilai, an anti-aging researcher at Albert Einstein College of Medicine in New York. "We don't know enough about the commonalities in order to target with one drug all the senescent cells," he says. "We always talk about senescent cells as if every senescent cell is the same, but that's been a gross oversimplification."
This is a problem on a much deeper level
The whole space is filling up, not with the snake oil sales men of days past, with decent scientists, like Sinclair, who are peddling all this junk, while at the same time, trying to replace Aubrey as the "rock star" face of the longevity space.
This is indeed "corrosive" to all good researchers who are working away at the bench doing real science
@dan petrov i take nmn, fisetin and also novos core which is a complex of well researched ingredients that have shown to have effects on aging and longevity. sens, calico, etc have yet to produce anything. i have no time to wait anymore and listen to false promises and speculative timeframes
Fisetin is still too weak a senolytic on it's own for humans. It can be enhanced by other substances (wogonin, lunasin, tyrosinase, luteolin, AHCC, delphinidin...?) yet this research is still not present. Nonetheless, it's properties that enable quercetin, curcumin and resveratrol (maybe others...?) to go through liver not metabolised (so biologically active) is its greatest value.
"The Supplement industry"? I read here about Elysium. The alternative is the drug industry -having the biggest and best funded lobby in Congress. Don't wonder why people reject vaccination science, they have little trust in a system corrupted by money. Polls say much the same about media.
I recently went to my 50th High School Reunion. Do we have a full explanation for aging and its cure? A cure for cancer? Energy too cheap to meter? Bases on the moon and Mars?
Too many things didn't happen. Something is very wrong.
... and while the supplement industry likes to lie about, ommit and distort findings from studies, the 'science' itself is way too often only reproducible in photoshop, esp. in aging and cancer related fields.
This is basically what Unity's UBX0101 senolytic approach was based on (enjoy the comment section):
MDM2-dependent downregulation of p21 and hnRNP K provides a switch between apoptosis and growth arrest induced by pharmacologically activated p53
https://pubpeer.com/publications/F5D947C61E8B23CCD1EB716E4A1059
You can find dozens of such examples w.r.t. mTOR or Sirtuin research and some other favourites of the anti-aging community.
For examples look here
https://forbetterscience.com/2020/11/23/mtor-conclusions-not-affected/
and here (see ยง 'Sinclair papers')
https://forbetterscience.com/2020/05/14/never-ageing-anti-aging-to-cure-covid-19/
Stanford puts it like this '"reproducibility crisis" and "replication crisis" gained currency in conversation and in print over the last decade'. I just think of it as fraud.
After Goldman Sachs said that finding cures is not a viable business model, we might consider that the supplement industry, together with DIY approaches, might produce the bulk of useful anti aging treatments. Maybe China could create some progress if an aging demographic inhibits their economy.
One study is highly significant: a 2011 paper, published in PLOS ONE, suggesting a compound called NAD+ played a major role in staving off the ageing process; it has been cited more than 400 times. This "seminal" study underpinned work around the world to develop anti-ageing drugs that increased NAD+, according to the study's lead author Dr Nady Braidy.
https://pubpeer.com/publications/FEA0DF96057EC76032D25CED4F86BE
Guess what... completely fake...
This clinical trial (Kirkland is PI) of fisetin for frailty should read out soon. The study completion date says 11/28/2021
https://clinicaltrials.gov/ct2/show/NCT03675724
@David I don't think so. But who knows, maybe JLK pulls off a turbo study from unfinished recruiting to publication in just 5 or so weeks. ;p
Recruitment Status : Recruiting
First Posted : September 18, 2018
Last Update Posted : February 24, 2021
There is literature pointing to synergistic rather than additive biological action with small molecule combinations. Polyphenols (fisetin, quercetin, catechin, resveratrol, luteolin, tyrosol, berberine, many others, comprise a library of small molecules that make their way into cells and the nucleus to exert genetic influence.
The dietary supplement industry is an industry that can deliver anti-aging pills economically. Good Manufacturing Practices minimize poor/inconsistent quality supplements. However, the supplement industry has a muzzle over its mouth, it cannot make any claims it prevents, treats or cures any disease, and aging is included.
Are there studies that confirm that the hit and run high dose is more effective than a 30-fold lower daily dose? I know that the hit and run high dose is theorized by researchers to be more effective, but do we have any animal studies that compare the two dosing strategies?
Thank you for posting this piece, Reason! I think this is such an important call you are making - supplements industry should at the least be providing good data on what's included in the products. But instead a lot of it is marketing and exorbitant prices!