So far, its effects have been dramatic (in a good way) in mice; human trials are now underway.

How does it work?

It builds from previous work, in which a Japanese research team created an “anti-aging vaccine”, that responded to a problem more specific than aging as a whole, namely atherosclerosis.

They found that a certain* protein was upregulated (i.e., it was made at a greater rate resulting in greater quantities) in patients (mouse and human alike) with atherosclerosis. So, they immunized the mice against that protein, and long story short, everything improved for them, from their atherosclerosis to general markers of aging—including growing back fur that had been lost due to age-related balding (just like in humans). They also lived longer, as is to be expected of a mouse who is now biologically younger.

*To avoid being mysterious: it was glycoprotein nonmetastatic melanoma protein B, known to its friends as GPNMB.

You may be wondering: how can one be immunized against a protein? If so, do bear in mind, a virus is also a protein. In this case, they developed an RNA vaccine, that works in a similar way to the COVID vaccines we all know and love (albeit with a different target).

You can read about this in abundant detail here: Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice

Hot on the heels of that, new approaches were found, including…

The combination

We’ll not keep you waiting; the combination is dasatinib plus quercetin, or else fisetin alone.

It’s about killing senescent (aging) “zombie cells” while sparing healthy cells, which that drug (dasatinib) and those supplements (quercetin and fisetin) do.

The researchers noted:

❝Senescent cells are resistant to apoptosis, which is governed through the upregulation of senescent cell anti-apoptotic pathways (SCAPs). Compounds were subsequently identified that disrupted the SCAPs, inducing death of senescent cells while leaving healthy cells unaffected. Forty-six potential senolytic agents were discovered through this process. To advance translational efforts, the majority of research has focused on agents with known safety profiles and limited off-target effects (Kirkland and Tchkonia, 2020).

The best characterized senolytic agents are dasatinib, a tyrosine kinase inhibitor approved for use in humans for cancer treatment, and quercetin, a naturally occurring plant flavonoid. The agents have a synergistic effect, making their combination more potent for senescent cell clearance (Zhu et al., 2015). As senescent cells do not divide and accumulate over a period of weeks, they can be administered using an intermittent approach, which further serves to reduce the risk of side effects (Kirkland and Tchkonia, 2020).

In preclinical trials, the combination of dasatinib and quercetin (D + Q) have been found to alleviate numerous chronic medical conditions including vascular stiffness, osteoporosis, frailty, and hepatic stenosis❞

Source: A geroscience motivated approach to treat Alzheimer’s disease: Senolytics move to clinical trials

As to how they expanded on this research:

❝In our study, oral D + Q were intermittently administered to tau transgenic mice with late-stage pathology (approximated to a 70-year-old human with advanced AD) (Musi et al., 2018). The treatment effectively reduced cellular senescence and associated senescence-associated secretory phenotype incidence. The 35 % reduction in neurofibrillary tangles was accompanied by enhanced neuron density, decreased ventricular enlargement, diminished tau accumulation, and restoration of aberrant cerebral blood flow. A subsequent preclinical study validated the findings, reporting that intermittently administered D + Q cleared senescent cells in the central nervous system, reduced amyloid-β plaques, attenuated neuroinflammation, and enhanced cognition❞

Source: Ibid.

And now taking it to humans:

❝The first clinical trial of D + Q for early-stage Alzheimer’s Disease (AD) has completed enrollment (Gonzales et al., 2021). The primary aim of the open-label pilot study was to examine the central nervous system penetrance of D and Q in a small sample of older adults with early-stage AD (NCT04063124). In addition, two placebo-controlled trials of D + Q for neurodegenerative disease are underway (NCT04685590 and NCT04785300).

One of the trials in development is a multi-site, double-blind, randomized, placebo-controlled study of senolytic therapy in older adults with amnestic mild cognitive impairment (MCI) or early-stage dementia (Clinical Dementia Rating Scale (CDR) Global 0.5–1) due to AD (elevated CSF total tau/Aβ42 ratio).

The treatment regimen will consist of 12-weeks of intermittently administered oral D + Q.❞

Source: Ibid.

The study is actually completed now, but its results are not yet published (again, at time of writing). Which means: they have the data, and now they’re writing the paper.

We look forward to providing an update about that, when the paper is published!

In the meantime…

Dasatinib is a drug usually prescribed to people with certain kinds of leukemia, and suffice it to say, it’s prescription-only. And unlike drugs that are often prescribed off-label (such as metformin for weight loss), getting your doctor to prescribe you an anticancer drug is unlikely unless you have the cancer in question.

You may be wondering: how is an anticancer drug helpful against aging? And the answer is that cancer and aging are very interrelated, and both have to do with “these old cells just won’t die, and are using the resources needed for young healthy cells”. So in both cases, killing those “zombie cells” while sparing healthy ones, is what’s needed. However, your doctor will probably not buy that as a reason to prescribe you a drug that is technically chemotherapy.

Quercetin, on the other hand, is a readily-available supplement, as is fisetin, and both have glowing (in a good way) safety profiles.

Want to know more?

You can read more about each of quercetin and fisetin (including how to get them), here:

• Querying Quercetin
• Fisetin: The Anti-Aging Assassin

Enjoy!