https://www.nature.com/articles/s41587-025-02740-7
I agree with the author in essence on this.
Summary via O3
Summary of “Senolytics under scrutiny in the quest to slow aging” (Nature Biotechnology, 2025)
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Why the excitement?
With global populations aging, drugs that delay biological aging promise vast health and financial benefits. Because senescent cells accumulate with age and secrete pro-inflammatory SASP factors, selectively killing them with “senolytics” has become one of the most hyped strategies in longevity biotechnology. A 2016 mouse study showing ~25 % lifespan extension after genetic ablation of p16-positive cells turbo-charged interest in finding drug equivalents. -
Flagship trials have stumbled.
Unity Biotechnology repurposed anti-cancer agents as senolytics (UBX0101 for osteoarthritis; UBX1325 for diabetic macular edema). Both compounds failed to beat standard care in phase-2 trials, casting doubt on whether current senolytics truly confer clinical benefit. -
Mixed results in mice.
Early reports of modest lifespan gains (e.g., 11 % with fisetin) have not held up in larger, more rigorous Interventions Testing Program studies, which found no survival benefit or senescent-cell reduction with long-term fisetin dosing. -
Key scientific hurdles:
- Specificity – Many senolytics are blunt anti-cancer drugs that can harm healthy cells (e.g., BCL-xL inhibitors are platelet-toxic).
- Defining the target – “Senescent cell” is a heterogeneous category lacking universal biomarkers; different tissues harbor distinct SASP profiles.
- Physiological roles – Senescent cells aid wound healing, development and metabolic regulation; their wholesale removal can worsen outcomes (e.g., barrier disruption, liver injury, β-cell function).
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Diversifying tactics.
Start-ups are broadening the toolkit beyond cell-killing small molecules to CAR-T and antibody therapies, antisense oligos, gene therapies, and “senoblockers” that mute harmful SASP signals without eradicating the cells (Table 1 of the paper lists more than a dozen such companies). -
Bottom line.
The author concludes that, while clearing specific senescent-cell populations might still treat certain inflammatory or fibrotic diseases, present-generation senolytics have not delivered a convincing path to broadly slow or reverse human aging. Robust longevity benefits, safety, and clear biomarkers remain unresolved, so enthusiasm should be tempered with rigorous long-term studies.