A 2025 paper in Aging and Disease reports that long-term therapy with Dasatinib + Quercetin (“D+Q”) produces robust reversal of age-related vascular dysfunction in old mice. Over eight months of biweekly treatment, senescence markers in mesenteric artery endothelial cells (p21 expression, SA-β-gal positivity) fell sharply, coincident with restored acetylcholine-induced vasodilation and improved blood-flow responses — hallmarks of rejuvenated nitric oxide (NO) signaling and endothelial health. On a subcellular level, mitochondrial morphology normalized, reactive oxygen species (ROS) production dropped, and eNOS (endothelial nitric oxide synthase) re-dimerized into its functional form — indicating that senolytic clearance re-enabled mitochondrial/NO homeostasis rather than simply masking damage.
The study thus strengthens the view that senescent endothelial cells are functional drivers — not just passive markers — of vascular aging. Clearing them can reinstate vascular responsiveness and mitochondrial fitness in aged tissue. For longevity-oriented interventions, these data support the idea that intermittent, long-term senolytic treatment might one day form part of vascular rejuvenation strategies aiming to reduce arterial stiffness, improve microcirculation, and perhaps delay cardiovascular-age–related morbidity.
Limitations: Study Design, Publication Context, and Translational Gaps
1. Animal model & limited vascular beds. The experiment was conducted in mice, focusing on mesenteric arteries — small resistance vessels. It remains unknown whether similar effects would occur in large elastic arteries (e.g., aorta, carotid) or human vascular beds, where geometry, shear stress, and senescence dynamics differ considerably.
2. Singular research group, short-term safety evaluation. The research was performed by a group led by authors including Jie Lin et al., and published as a “Short Communication,” which may imply a smaller scale or preliminary nature. There is minimal reporting on systemic off-target effects, immune consequences, or long-term safety. Given that D+Q involves a tyrosine-kinase inhibitor (Dasatinib) plus a flavonoid (Quercetin), chronic administration in humans could carry risks — especially in non-target tissues. This single-group provenance raises concerns about reproducibility and robustness; independent replication will be critical.
3. Publication venue and peer-review context. The journal has a reasonable impact factor (~9.9 as of 2021) and is open-access, indexed broadly. Nevertheless, the “Short Communication” format may have been subject to limited peer-review depth compared to full-length articles, increasing the risk that subtle methodological or statistical issues remain unexamined.
4. Translational uncertainty & lack of human data. While preclinical evidence for senolytics continues to accumulate (e.g., for metabolic, bone, and disc degeneration contexts) — human data remain sparse and inconsistent. For example, a recent longitudinal human senolytic pilot found no consistent epigenetic-age deceleration, and in some measures, modest age-acceleration or telomere shortening after D+Q treatment. This underscores that even if endothelial senescence can be cleared in humans, it may not translate into broad “rejuvenation,” or may come with trade-offs.
Conclusion (with cautious optimism)
This new preclinical work compellingly demonstrates that chronic senolytic therapy can reverse key aspects of vascular aging — mitochondrial dysfunction, endothelial senescence, and impaired NO-dependent vasodilation — at least in mice. For the longevity field, it provides additional support for the hypothesis that senescent-cell clearance may be a mechanistic lever for vascular rejuvenation.
However — the research remains early, rooted in a single group’s mouse study, with limited safety data, narrow tissue scope, and no human validation. Before considering translation (or advocating D+Q use in humans), the following are essential: independent replication, expanded analyses of systemic effects (immune, hemostatic, clearance capacity), dose-finding safety studies, and carefully controlled human trials with vascular and functional endpoints.
Open access paper: Long-term Senolytic Treatment Prevents Endothelial Dysfunction in Arterial Aging