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categories: ["longevity"]categories: ["longevity"]tags: ["cellular senescence", "aging", "sasp", "clinical trials", "drug repurposing", "apoptosis"]tags: ["cellular senescence", "aging", "sasp", "clinical trials", "drug repurposing", "apoptosis"]summary: "Drugs that selectively kill senescent cells, an approach that reduces age-related pathology in mice but has so far produced modest or null results in humans."summary: "Drugs that selectively kill senescent cells, an approach that reduces age-related pathology in mice but has so far produced modest or null results in humans."updated: "2026-08-23"updated: "2026-10-28"humanEvidence: "Human data are small open-label pilots of nine to fourteen patients, one showing reduced senescent-cell markers in fat and skin, plus two randomized failures; every lifespan result is from mice."humanEvidence: "Human data are small open-label pilots of nine to fourteen patients, one showing reduced senescent-cell markers in fat and skin, plus two randomized failures; every lifespan result is from mice."access: "No senolytic is approved for any aging indication; dasatinib is an approved cancer drug available only on prescription, and fisetin and quercetin are sold over the counter as supplements at doses taken from mouse studies."access: "No senolytic is approved for any aging indication; dasatinib is an approved cancer drug available only on prescription, and fisetin and quercetin are sold over the counter as supplements at doses taken from mouse studies."reversibility: "partly-reversible"reversibility: "partly-reversible"lines 130–143 → 130–169115 unchanged lines not shown
macular edema, has produced phase 2 data the company describes as favourable; an independentmacular edema, has produced phase 2 data the company describes as favourable; an independentconfirmatory trial had not been published as of 2026.confirmatory trial had not been published as of 2026. Beyond small molecules, cardiac glycosides such as ouabain and digoxin have been reported to haveBeyond these compounds, cardiac glycosides such as ouabain and digoxin have been reported to havebroad senolytic activity, and immunological approaches (senolytic CAR T cells directed atbroad senolytic activity. Researchers have also exploreduPAR,[^amor2020] and vaccines raised against senescence-associated surface antigens) offer the[[gene-therapy-for-aging|gene-delivered constructs]] that place a killing gene under the control ofprospect of a single treatment with lasting effect rather than repeated dosing. Researchers have alsoa senescence-responsive promoter, which would reproduce in a treatable animal what the INK-ATTACexplored [[gene-therapy-for-aging|gene-delivered constructs]] that place a killing gene under thetransgene achieved by design.control of a senescence-responsive promoter, which would reproduce in a treatable animal what theINK-ATTAC transgene achieved by design. ### Immune-based clearance A second route enlists the immune system, which the SASP already recruits to remove some senescentcells and whose own decline is treated under [[immunosenescence]]. The approach needs a surfaceprotein enriched on senescent cells for engineered T cells or antibodies to recognise. Amor andcolleagues identified the urokinase plasminogen activator receptor (uPAR) as one, and showed thatCAR T cells directed against it cleared senescent cells in mice and restored tissue homeostasis inchemically and diet-induced liver fibrosis.[^amor2020] In a 2024 follow-up the same group reportedthat uPAR-positive cells accumulate with age in mice, and that a single infusion improved exercisecapacity and glucose tolerance in old mice and in mice on a high-fat diet, with effects that lastedand could also be achieved preventively.[^amor2024] Vaccination is the other strategy. Japanesegroups immunised mice against GPNMB, a membrane protein enriched on senescent vascular endothelialcells, which reduced GPNMB-positive cells, improved several age-related phenotypes, and extendedlifespan in male progeroid mice; a vaccine against CD153 reduced senescent T cells in the fat ofobese mice.[^suda2021] The appeal is durability: one treatment rather than repeated drug courses. The same property is themain concern. Engineered T cells that persist, or an antibody response that lasts months, cannot bewithdrawn the way a short drug course can; CAR T therapy carries the cytokine-release toxicity knownfrom its cancer use; and neither uPAR nor GPNMB is unique to senescent cells, so normal cellscarrying the target are exposed too. Every result above is from mice, and no immune-based senolytichad reported data in people as of October 2026. Immorta Bio said in October 2026 that it hadcompleted preclinical studies of SenoMune-0257, a synthetic nine-amino-acid peptide it identified using[[ai-drug-discovery|artificial intelligence]] to stimulate cytotoxic T cells against senescentcells, and that itexpected initial human evaluation before the end of the year; no peer-reviewed data on the peptidehad been published as of October 2026.[^immorta2026] ## Human evidence## Human evidence The human record is short and must be read carefully. The idiopathic pulmonary fibrosis pilotThe human record is short and must be read carefully. The idiopathic pulmonary fibrosis pilotlines 248–253 → 274–282104 unchanged lines not shown
[^justice2019]: `paper` Justice, J.N. et al. "Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study." *EBioMedicine*, 2019.[^justice2019]: `paper` Justice, J.N. et al. "Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study." *EBioMedicine*, 2019.[^hickson2019]: `paper` Hickson, L.J. et al. "Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease." *EBioMedicine*, 2019.[^hickson2019]: `paper` Hickson, L.J. et al. "Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease." *EBioMedicine*, 2019.[^amor2020]: `paper` Amor, C. et al. "Senolytic CAR T cells reverse senescence-associated pathologies." *Nature*, 2020.[^amor2020]: `paper` Amor, C. et al. "Senolytic CAR T cells reverse senescence-associated pathologies." *Nature*, 2020.[^amor2024]: `paper` Amor, C. et al. "Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction." *Nature Aging*, 2024.[^suda2021]: `paper` Suda, M. et al. "Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice." *Nature Aging*, 2021; and Yoshida, S. et al. "The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice." *Nature Communications*, 2020.[^immorta2026]: `statement` Immorta Bio. "Immorta Bio Pioneers AI-Designed Senolytic Immunotherapy Targeting Diseases of Aging." Press release, PR Newswire, 12 October 2026. {The company describing its own unpublished work; the release gives no quantitative preclinical results and names no IND or trial registration.}[^grosse2020]: `paper` Grosse, L. et al. "Defined p16High senescent cell types are indispensable for mouse healthspan." *Cell Metabolism*, 2020. {Clearance here was genetic and sustained rather than a short drug course, so the result bounds the hazard of indiscriminate clearance without measuring what an intermittent senolytic would do.}[^grosse2020]: `paper` Grosse, L. et al. "Defined p16High senescent cell types are indispensable for mouse healthspan." *Cell Metabolism*, 2020. {Clearance here was genetic and sustained rather than a short drug course, so the result bounds the hazard of indiscriminate clearance without measuring what an intermittent senolytic would do.}[^farr2024]: `paper` Farr, J.N. et al. "Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a randomized controlled trial." *Nature Medicine*, 2024.[^farr2024]: `paper` Farr, J.N. et al. "Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a randomized controlled trial." *Nature Medicine*, 2024. removed, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.
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