Systematic review in BJCP finds human clinical data for senolytics and senomorphics remains investigational

A systematic review in the British Journal of Clinical Pharmacology reports that while targeting cellular senescence is clinically feasible, existing human trial data are insufficient to establish efficacy or long-term safety.

Researchers conducted a systematic review and qualitative narrative synthesis following PRISMA 2020 guidelines to analyze pharmacological interventions targeting cellular senescence in humans.

The evidence synthesis evaluated six completed clinical studies and identified one ongoing clinical trial.

Senolytic therapies, particularly the combination of dasatinib and quercetin, demonstrated preliminary improvements in selected functional outcomes and reductions in senescence-associated biomarkers.

Senomorphic and mTOR-targeting therapies demonstrated measurable effects on specific tissue and immune-related clinical outcomes.

Reported adverse events were generally mild and manageable, but small sample sizes and brief follow-up periods limited the assessment of uncommon or long-term safety risks.

Targeting senescent cells represents a major paradigm shift in translational geroscience, but translating preclinical efficacy to human clinical validation remains a key bottleneck.

The review establishes that while senotherapeutic interventions are biologically active and feasible in humans, they must still be considered strictly investigational rather than established therapies.

A lack of standardized senescence biomarkers and insufficient statistical power across completed trials are highlighted as critical hurdles preventing definitive efficacy conclusions.

Developers of senolytics and senomorphics are likely to face increased pressure from both regulators and capital markets to utilize standardized, validated biomarkers of senescence to prove clinical activity.

The clinical-stage pipeline in this sector is highly dependent on moving past small-scale pilot studies and into larger, adequately powered randomized controlled trials with extended follow-up windows to establish definitive safety profiles.

The initiation of larger, randomized trials adopting standardized senescence biomarkers and long-term follow-up protocols to establish clinical safety and efficacy.