Targeting Cellular Senescence With Senolytics to Improve Skeletal Health in Older Humans

Summary

To determine if senolytic drugs reduce senescent cell burden and reduce bone resorption markers/increase bone formation markers in elderly women.

Timeline

Start

2020-06-09

Primary completion

2023-06-06

Completion

2023-06-06

Outcome

Missed primary endpoint

paper The primary endpoint, percentage changes at 20 weeks in the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx), did not differ between groups PMID 38956196 ↗

paper D + Q -4.1% (-13.2, 2.6), control -7.7% (-20.1, 14.3); P = 0.611 PMID 38956196 ↗

Publications

• Farr JN, Monroe DG, Atkinson EJ, Froemming MN, Ruan M, LeBrasseur NK, Khosla S. Characterization of Human Senescent Cell Biomarkers for Clinical Trials. Aging Cell. 2025 May;24(5):e14489. doi: 10.1111/acel.14489. Epub 2025 Jan 17.
• Farr JN, Atkinson EJ, Achenbach SJ, Volkman TL, Tweed AJ, Vos SJ, Ruan M, Sfeir J, Drake MT, Saul D, Doolittle ML, Bancos I, Yu K, Tchkonia T, LeBrasseur NK, Kirkland JL, Monroe DG, Khosla S. Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial. Nat Med. 2024 Sep;30(9):2605-2612. doi: 10.1038/s41591-024-03096-2. Epub 2024 Jul 2.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Fisetin	Small molecule	20 mg/kg	Oral
Subject	Quercetin	Small molecule	1000 mg	Oral
Subject	dasatinib anhydrous	Small molecule	100 mg	—

Indications

No indication recorded.