Senolytics hit the clinic: three 2025 trials define the turn

2025 is the year senolytics step into human medicine

For a decade, senolytics lived in mouse papers and podcast optimism. The premise is simple: clear senescent cells that accumulate with age and stress, and tissues work better. In 2025 the field shifts from could to will. Three trials updated or launched this year form a real human evidence base: a St. Jude randomized head-to-head of dasatinib plus quercetin versus fisetin in adult survivors of childhood cancer, Washington University’s SToMP-AD Phase II in early Alzheimer’s, and a new NIH-backed trial testing dasatinib plus quercetin for frailty in people aging with HIV. St. Jude’s design and endpoints are public under the St. Jude D+Q vs fisetin protocol, and SToMP-AD is listed on the SToMP-AD Phase II registry.

If you care about the first real indications for aging biology, watch these three. They target accelerated aging cohorts where senescence burden is high and measurable over months, not decades. They also converge on a dosing idea regulators can live with: short, intermittent pulses instead of chronic daily therapy.

The regulatory wedge: intermittent, time-boxed dosing

Intermittent dosing is not just pharmacology. It is the strategy that makes senolytics easier to justify to ethics boards, monitors, and regulators.

Finite exposure: brief bursts with long drug holidays reduce cumulative toxicity and concentrate safety monitoring windows.
Biology-aligned: senescent cells do not regenerate daily. Periodic debulking fits the mechanism.
Operationally simple: sites cluster labs and adverse event checks around dosing days, then space out off-drug visits.

How the 2025 programs apply pulses

St. Jude survivors with frailty: randomized to D+Q on days 1 to 3 then 30 to 32, or fisetin on days 1 to 2 then 30 to 31. Primary endpoints land at day 60, with durability follow-up around day 150. Structure is detailed in the St. Jude D+Q vs fisetin protocol.
Early Alzheimer’s disease: SToMP-AD repeats two days on and 13 days off across 12 weeks, with cognitive and functional outcomes plus target engagement markers, per the SToMP-AD Phase II registry.
People aging with HIV: the NIH-backed frailty study plans six cycles over 12 weeks, two dosing days per cycle with 12 days off, aiming to improve physical function while tracking senescence biology.

Endpoints that could actually move FDA

No single biomarker will unlock approval, but these trials triangulate a package regulators recognize.

Frailty and physical function

Gait speed over 4 meters: objective, quick, and strongly linked to hospitalization, disability, and mortality. Expect change at day 60 to be pivotal, with durability at day 150.
Grip strength and chair stands: complementary readouts, plus composite frailty indices and count of reversed Fried criteria.

Cellular senescence load

p16INK4a in CD3+ T cells: a prespecified biological endpoint in survivor cohorts, responsive to chemotherapy exposure and age. A durable drop would support on-target action.
SASP composites: multi-analyte panels reported as z-score shifts. Coherent declines across IL-6, MMPs, and related factors beat single cytokine changes.

For context on how biomarker strategy is evolving, see our explainer on the FDA LDT reversal reshapes biomarkers and why large proteomic resources like the UK Biobank proteome dataset matter for assay validation.

Disease-specific outcomes

Alzheimer’s: SToMP-AD tracks CDR-SB and ADAS-Cog slopes over 48 weeks, with an early dosing window and longer observation tail. Even small separations paired with on-target SASP shifts would be notable.
HIV and aging: look for gait speed, the Veterans Aging Cohort Study Index, and patient-reported quality of life. Movement in VACS alongside function would resonate with regulators.

Safety watch-outs that will decide the field

Senescence is double-edged. Senolytics often repurpose oncology agents, so trials are tuned for known liabilities.

Myelosuppression: dasatinib can depress counts. Protocols screen baselines, time CBCs around dosing, and set conservative stop rules.
Fluid and cardiac effects: pleural effusions and QT prolongation are monitored with ECGs and exclusions for recent cardiac events.
Drug interactions: dasatinib is a CYP3A4 substrate and sensitive to gastric pH. Many designs restrict PPIs and strong CYP3A4 modulators during dosing windows.
Off-target tissue effects: delayed wound healing risk drives exclusions around recent surgery.
Hepatic and renal thresholds: transaminase or eGFR shifts are watched closely, with intermittent exposure designed to minimize risk.

The safety bar for a preventive aging drug is high. The bar for a finite course that moves frailty and function is more approachable.

Why accelerated aging cohorts are the right first indications

You do not need to enroll 5,000 community-dwelling 75-year-olds and wait five years if you test where senescence biology is dialed up now.

Adult survivors of childhood cancer: chemotherapy and radiation leave a senescence imprint. Many survivors in their 30s and 40s meet frailty criteria and show elevated p16INK4a.
People aging with HIV: chronic immune activation plus historical toxic exposures accelerate biological aging. Frailty and slow gait present earlier.
Early Alzheimer’s with tau positivity: preclinical links between tau and glial senescence plus CSF penetration signals support testing. For adjacent approaches in neurodegeneration, see our take on Retro's autophagy Alzheimer's trial.

How a win could roll out from here

From biology to label: first approvals, if they come, will likely be disease-framed such as frailty in defined survivor populations, functional impairment in people with HIV on stable ART, or early Alzheimer’s with tau positivity.
Companion diagnostics: baseline enrichment by p16INK4a or SASP composites could enable future diagnostics and payer alignment.
Standardized pulse regimens: two days on, 12 to 13 days off, repeated for six cycles may become clinic routine.
Combination thinking: senescent cell clearance could pair with rehabilitation, strength training, and disease-specific therapies.

What to watch next

Feasibility: completion of all dosing cycles and follow-ups without major issues.
Biomarker coherence: consistent p16INK4a and SASP declines with partial persistence at day 60 to 150.
Function first: clinically meaningful gains in gait speed that align with biomarker change.
Disease outcomes: directional benefits on CDR-SB or ADAS-Cog in SToMP-AD, and movement in VACS for the HIV trial.
Safety adjudications: DSMB notes on myelosuppression, fluid events, and cardiac signals.

The bottom line

Senolytics are not a fountain of youth. They are housekeeping delivered in pulses. 2025 looks like an inflection because three credible programs aligned on the same bet: brief, intermittent clearance of senescent cells can move biology and function in people whose aging has been accelerated by cancer therapy, chronic infection, or neurodegeneration. A clean functional win with coherent biomarkers would mark the first real indications for medicines that act on aging pathways and would set the stage for broader questions the field has waited a decade to test.