Senolytics

What are senolytics?

Senolytics are compounds that selectively kill senescent cells, often called "zombie cells," which have permanently stopped dividing but refuse to die. These dysfunctional cells pile up with age and pump out a toxic mix of inflammatory molecules known as the senescence-associated secretory phenotype (SASP). This chronic, low-grade inflammation drives tissue damage and speeds up age-related diseases like cardiovascular disease, neurodegeneration, osteoarthritis, and cancer. The goal of senolytic therapy is straightforward: clear these cells, cut the inflammation, and restore healthier tissue function.

How senolytic drugs work

Senescent cells dodge the body's normal cell-death programs by cranking up anti-apoptotic (pro-survival) pathways, particularly the BCL-2 family of proteins. Senolytics exploit this weakness. By blocking these survival signals, they push senescent cells toward programmed cell death (apoptosis) while leaving healthy cells alone. Different compounds hit different targets: some inhibit tyrosine kinases, others block BCL-2/BCL-xL proteins, and natural polyphenols appear to disrupt multiple senescent cell defenses at once ^[1].

Because senescent cells don't divide and take weeks to re-accumulate after clearance, senolytics can be dosed intermittently rather than daily. This "hit-and-run" approach reduces side effect exposure while maintaining effectiveness. Most research protocols use two to three consecutive dosing days per month ^[2].

Key senolytic compounds

The most studied senolytic combination is dasatinib plus quercetin (D+Q), developed by researchers James Kirkland and Tamar Tchkonia at the Mayo Clinic. Dasatinib, a tyrosine kinase inhibitor originally built for leukemia, targets senescent fat cell precursors. Quercetin, a plant flavonoid from onions, apples, and berries, goes after senescent endothelial cells. Together, they cover a wider range of senescent cell types than either compound alone ^[2].

Fisetin, a flavonoid found in strawberries and persimmons, came out on top in a screen of ten flavonoids as the strongest natural senolytic. In aged mice, it cut senescent cell burden and extended median lifespan by roughly 10% ^[3]. Navitoclax (ABT-263), a pharmaceutical BCL-2/BCL-xL inhibitor, is potent against senescent blood and endothelial cells but carries a real risk of thrombocytopenia because it also shortens platelet lifespan ^[4]. Piperlongumine from long pepper is another natural candidate under active preclinical study.

Senolytics supplements: what's available

The senolytics supplements market has grown rapidly, with products typically built around fisetin, quercetin, or combinations of both. Dasatinib is a prescription drug and not available over the counter. Among supplement options, fisetin has the strongest preclinical backing as a standalone senolytic. Quercetin is widely available and inexpensive, though its senolytic effect appears weaker without dasatinib. Some commercial formulations add piperlongumine, luteolin, or curcumin for broader coverage. Evidence for these combinations in humans is still thin, so treat marketing claims with skepticism and consult a doctor before starting any senolytic regimen.

Clinical trials and evidence

Human senolytic research is progressing fast. The first-in-human senolytic trial showed D+Q improved physical function in patients with idiopathic pulmonary fibrosis. The SToMP-AD pilot study tested D+Q in older adults at risk for Alzheimer's disease and found the regimen safe and feasible, with reductions in inflammatory biomarkers that correlated with cognitive improvements ^[5]. A Phase 2 trial in postmenopausal women with osteoporosis showed subtle but measurable bone health effects ^[6]. More than 30 clinical trials are completed, underway, or planned for conditions including diabetic kidney disease, frailty, and childhood cancer survivorship.

A longitudinal study examined whether senolytics affect biological age as measured by DNA methylation clocks. D+Q alone showed increases in epigenetic age acceleration at 3 and 6 months, but adding fisetin to the protocol appeared to mitigate this effect, suggesting that fisetin may buffer some of the epigenetic impacts of dasatinib ^[8]. A 2026 preclinical breakthrough demonstrated clearance of 30-70% of zombie cells, and a new class of "senosensitizers" may overcome resistance in hard-to-clear populations ^[7].

Senolytics side effects and safety

Short-term side effects from D+Q in clinical trials have been mild, mostly gastrointestinal discomfort. Dasatinib, however, is a powerful pharmaceutical with known risks at oncology doses, including neutropenia, thrombocytopenia, and pleural effusion. These risks appear lower with the intermittent senolytic dosing schedule, but long-term safety data is still limited. Fisetin and quercetin supplements have a cleaner safety profile, though they can interact with blood-thinning medications and CYP3A-metabolized drugs. Anyone taking prescription medications should check with their doctor first.

Natural senolytics in food

Several senolytic compounds occur naturally in everyday foods, though at concentrations far below therapeutic doses. Quercetin is found in capers, red onions, cranberries, and leafy greens. Fisetin is present in strawberries, apples, persimmons, and cucumbers. Luteolin, structurally close to quercetin, shows up in celery, parsley, and chamomile tea. Dietary intake alone won't achieve clinical senolytic effects, but regular consumption of flavonoid-rich foods supports a broader anti-inflammatory pattern that may slow the rate at which senescent cells accumulate.

Senolytics vs. senomorphics

Senolytics kill senescent cells. Senomorphics suppress their harmful SASP output without eliminating the cells themselves. Rapamycin, metformin, and certain JAK inhibitors fall into the senomorphic category. Some researchers think the best approach combines both: senolytics for periodic clearance and senomorphics for ongoing SASP suppression between doses. An emerging third strategy uses engineered CAR-T cells to hunt senescent cells by targeting surface markers like uPAR. In mice, senolytic CAR-T cells persisted for up to 12 months after a single treatment and prevented age-related metabolic decline ^[9]. Clinical translation of all these approaches remains early-stage, but the field is one of the most active frontiers in longevity science.