Do senolytics already work in humans, or only in mice so far?

Senolytics do not only work in mice: small but concrete steps have now been taken in humans. The best-known combination is dasatinib plus quercetin. In a pilot study with 9 patients with diabetic kidney disease, a course of just 3 days was enough to produce a measurable reduction in senescent cells in fat tissue and skin. Within 11 days, inflammatory markers in the blood also fell detectably. This is the first direct evidence that senolytics actually remove senescent cells in humans, but 9 patients without a control group is too few to say whether this also leads to long-term health benefits.

In cancer treatment, the results are somewhat further along. In 51 patients with head and neck cancer, a combination of senolytics with immunotherapy achieved a major pathological response in one third of participants, with few serious side effects (grade 3 or 4 in only 4.2%). A proof-of-concept study in prostate cancer also showed clinical benefit in a subset of patients through a related approach: inhibiting the inflammation caused by senescent cells. These are promising early results, but randomised comparative trials are still lacking.

For other conditions, such as osteoarthritis and fertility problems caused by ageing of the endometrium, the evidence in humans is still almost non-existent. In osteoarthritis the mechanism is biologically plausible based on animal research, but clinical results are not yet available. In the endometrium the situation is additionally complicated: senescent cells also play a normal role there in embryo implantation, which makes developing safe senolytics for this organ particularly difficult.

Review articles emphasise that mouse studies are compelling, but that the translation to humans is still at an early stage. Results in mice do not automatically reproduce in humans, and questions about the right timing, dosage and long-term safety remain unanswered.