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Longevity & Cellular Health

Senolytic protocol

A senolytic protocol is a short, intermittent course of agents that selectively remove senescent cells, the damaged cells that stop dividing, resist their own death and secrete inflammatory signals into the surrounding tissue. St. George Hospital offers it inside the longevity program after biomarker testing, with the evidence stated as what it is: early and emerging.

What it is

What is a senolytic protocol?

Cellular senescence is a state in which a cell permanently stops dividing but does not die. Senescent cells accumulate in tissues with age and at the sites of chronic disease, and they secrete a mixture of inflammatory cytokines, chemokines and proteases known as the senescence-associated secretory phenotype (SASP). That secretion is one of the mechanisms linking age to chronic inflammation, fibrosis and immune dysfunction. St. George Hospital offers a senolytic protocol inside its longevity medicine work, as a short course within the healthy aging program, after biomarker testing and with the limits of the evidence stated in the consent.

The field is young. The first human studies were published in 2019, the first randomized trials in 2023 and 2024, and the researchers who developed the approach wrote in 2020 that, until the ongoing trials are done, it is too early for senolytics to be used outside clinical trials (Kirkland et al., J Intern Med, 2020). We quote that position because patients should hear it. Where we offer the protocol, it is an individual treatment attempt decided with the patient after medical consultation, and the biomarkers are measured before and after so that the attempt has a result you can see.

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How it works

How does it work?

Senescent cells survive their own damage by switching on anti-apoptotic pathways, among them the BCL-2 family and PI3K/AKT signaling. Senolytic agents briefly disable these survival networks, so that the senescent cell dies by apoptosis while healthy cells, which do not depend on those pathways in the same way, are spared. Because the target is a survival network rather than a receptor, the drugs need only be present for a short time, which is why the protocol uses intermittent dosing: one to three days, then weeks off.

The best-studied combination is dasatinib, a tyrosine kinase inhibitor licensed for leukemia, with quercetin, a plant flavonoid. Fisetin, another flavonoid, is used in some protocols and is under trial. Which agents, at what dose and over how many cycles, is decided by the attending physician from your biomarker profile, your medication list and your clinical state.

Diagram of the senolytic clearance: two tissue grids
Senolytic clearance in a tissue. Schematic, not to scale.
Who it is for

Who may benefit?

A senolytic protocol at St. George Hospital is considered for patients with:

  • Age-related functional decline documented in the healthy aging work-up
  • Raised markers of cellular senescence or chronic low-grade inflammation after other causes have been excluded
  • Chronic disease in which a senescent cell burden is suspected, discussed with the treating specialist
  • An interest in longevity medicine that accepts the current state of the evidence

The protocol is not offered as a treatment for any named disease. In oncology it is not given during active cancer treatment without the oncologist's agreement, and never as a replacement for standard therapy.

Could this belong in your plan?

That depends on your findings, not on the therapy. Write to the International Office with a short history; it requests your records afterwards, and a physician reviews them before the video consultation and tells you whether a senolytic cycle belongs in your program and which markers we would measure.

In the room

What the protocol looks like

  1. Before: baseline bloods on day one or two of the stay, including inflammatory markers (CRP, IL-6), liver and kidney values, a blood count and, where available, senescence-associated markers; an ECG for the QT interval; a review of every drug and supplement you take, because dasatinib interacts with CYP3A4 inhibitors, acid suppressants and anticoagulants.
  2. During: the agents are taken orally on one to three consecutive days, on the ward, with a physician check each day. The dosing days are undramatic. Most patients continue their other therapies, with infusions scheduled on the days between.
  3. After: a rest period of at least one week. The markers that were abnormal at baseline are repeated in week two, and the physician decides with you whether a second cycle belongs in this stay, in a follow-up visit, or not at all.

Evidence and safety

The animal work is extensive; the human evidence is small and recent, and we grade it as emerging. Side effects in the trials were mostly mild to moderate and limited to the dosing days and the days after.

Show studies, risks and side effects

The animal work behind senolytics is extensive. The human evidence is small, recent, and we grade it as emerging.

The first-in-human study gave dasatinib plus quercetin to fourteen patients with idiopathic pulmonary fibrosis on three days a week for three weeks, open-label and without a control group. All fourteen completed the course; walking distance, gait speed and chair-stand time improved, lung function and reported health did not change, and one serious adverse event occurred (Justice et al., EBioMedicine, 2019). The same year a three-day course in nine patients with diabetic kidney disease reduced senescent cell markers in fat tissue biopsies within eleven days, the first direct evidence that the drugs clear senescent cells in people (Hickson et al., EBioMedicine, 2019).

The randomized data are newer. A placebo-controlled pilot in twelve patients with pulmonary fibrosis found the three-week regimen feasible and without serious adverse events related to the drugs, but recorded more non-serious adverse events in the treated arm (65 versus 22), including sleep disturbance and anxiety, and no meaningful difference in function (Nambiar et al., EBioMedicine, 2023). A phase 2 randomized trial in postmenopausal women found that intermittent dasatinib plus quercetin did not reduce bone resorption in the group as a whole; a bone formation marker rose for a few weeks and then returned to baseline, no serious adverse events occurred, and in exploratory analysis the women with the highest senescent cell burden showed the clearest skeletal response (Farr et al., Nat Med, 2024). That last finding is the reason we measure burden before prescribing. What the evidence does not show is any effect on aging, lifespan or the course of a chronic disease in people.

Contraindications and side effects

  • Dasatinib: prolonged QT interval, significant liver disease, bleeding disorders or anticoagulation, pleural effusion in the history, pregnancy and breastfeeding. Strong CYP3A4 inhibitors or inducers that cannot be paused for the dosing days.
  • Active cancer under treatment, unless the treating oncologist agrees to the cycle.
  • Side effects reported in the trials: tiredness, gastrointestinal discomfort, skin irritation and bruising, respiratory symptoms, sleep disturbance and anxiety; mostly mild to moderate and limited to the dosing days and the days after.
Program

How it fits the program

The senolytic protocol is one block of the healthy aging program. It is scheduled after the diagnostic days and before the restoration phase, with NAD+ infusions and vitamin and glutathione infusions placed on the days between dosing days, and peptide therapy or IHHT where the work-up points there. Patients whose findings include a toxic burden have the detoxification program scheduled first. Our article on senolytic therapy and senescent cells explains the biology in more depth.

Costs: the protocol is billed as the prescribed agents, the biomarker testing and physician monitoring, as a therapy block inside your written, itemized cost overview. Costs are a package price plus individual add-ons, and a deposit is paid before admission. Treatment is self-pay; the invoice is itemized in English with diagnoses and procedure descriptions for out-of-network review. Details are on Costs and insurance and in the Information for international patients.

Questions

Frequently asked questions about the senolytic protocol

Is the senolytic protocol safe?

In the human studies so far, intermittent dasatinib plus quercetin over one to three weeks caused mostly mild to moderate effects: tiredness, gastrointestinal discomfort, skin bruising, respiratory symptoms, and in one trial more sleep disturbance and anxiety than placebo. Serious adverse events were rare and none was attributed to the drugs in the randomized pilot. Dasatinib is a leukemia drug with known interactions, so we check the ECG, liver values and your medication list before the first dose.

What does a cycle involve?

Baseline bloods including inflammatory markers and, where available, senescence-associated markers. Then one to three consecutive days of oral agents on the ward, with a physician check each day. Nothing dramatic happens on the dosing days. The markers are repeated in week two and the physician decides with you whether a second cycle belongs in the stay or in a follow-up visit.

Does it slow aging?

No human study has shown that. The trials so far have measured senescent cell markers in tissue, physical function in lung fibrosis and bone turnover in postmenopausal women, over weeks to months. Whether clearing senescent cells changes aging, lifespan or disease in people is unknown. We say this before the protocol is prescribed, and we offer it as an individual treatment attempt with that understanding.

How much does the senolytic protocol cost?

The protocol appears in your itemized cost overview as an add-on to the package price. You receive the estimate in EUR after a physician has read your findings and before anything is booked. Treatment is self-pay; the invoice is itemized in English for out-of-network review.

Who should not take senolytics?

Anyone with active cancer under treatment unless the oncologist agrees, because dasatinib is itself an oncology drug and interactions matter; people with a prolonged QT interval, significant liver disease, a bleeding disorder or on anticoagulants; pregnant or breastfeeding women; and anyone taking strong CYP3A4 inhibitors or inducers that cannot be paused. Your physician reviews all of this before the first dose.

If you want to know whether a senolytic cycle belongs in your plan, write a short inquiry to the International Office, free of charge; it asks for your findings afterwards. A physician reads them before the video consultation and tells you which markers we would measure first and what the cycle would contain. You can also read how a stay runs before you decide.

References

  1. Senolytic drugs: from discovery to translation.. J Intern Med 2020. PMID 32686219
  2. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study.. EBioMedicine 2019. PMID 30616998
  3. Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease.. EBioMedicine 2019. PMID 31542391
  4. Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability.. EBioMedicine 2023. PMID 36857968
  5. Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial.. Nat Med 2024. PMID 38956196

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