Translating Senolytics From Mice to Humans

TL;DR

This paper discusses the potential of senolytic drugs to improve health and lifespan in humans, based on promising rodent studies and early clinical trials.

Contribution

The paper highlights the need for personalized approaches in senolytic trials based on initial clinical findings and biological heterogeneity in aging.

Findings

Initial clinical trials suggest senolytics may improve healthspan biomarkers in humans.

There is a need to identify individuals with high senescent cell burdens for effective senolytic treatment.

Only 2 of 9 published trials included control groups, indicating a need for more rigorous study designs.

Abstract

Extensive studies in rodents have shown that senescent cells accumulate across tissues and their clearance leads to improvements in healthspan and lifespan. Based on these studies, there is intense interest in translating these findings into humans. Based on ClinicalTrials.gov, there are currently 26 ongoing studies on “senolytics” and 32 on “fisetin”. However, to date, there are only 9 published clinical trials of senolytics, only 2 of which included a control group. Collectively, the initial findings from these trials have indicated possible biological efficacy of senolytics (dasatinib + quercitin) in improving biomarkers of healthspan in humans with no significant safety concerns. However, these initial studies also highlight the potential heterogeneity of aging mechanisms in humans and argue for a more personalized approach in future senolytic trials. Specifically, it is likely going to be critical to identify aging individuals with a sufficiently high burden of senescent cells that would result in a beneficial effect from the senolytic intervention.