The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial
Open accessAbstract
Preclinical evidence demonstrates that senescent cells accumulate with aging and that senolytics delay multiple age-related morbidities, including bone loss. Thus, we conducted a phase 2 randomized controlled trial of intermittent administration of the senolytic combination dasatinib plus quercetin (D + Q) in postmenopausal women (n = 60 participants). 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 (median (interquartile range), D + Q -4.1% (-13.2, 2.6), control -7.7% (-20.1, 14.3); P = 0.611). The secondary endpoint, percentage changes in the bone formation marker procollagen type 1 N-terminal propeptide (P1NP), increased significantly (relative to control) in the D + Q group at both 2 weeks (+16%, P = 0.020) and 4 weeks (+16%, P = 0.024), but was not different from control at 20 weeks (-9%, P = 0.149). No serious adverse events were observed. In exploratory analyses, the skeletal response to D + Q was driven principally by women with a high senescent cell burden (highest tertile for T cell p16 (also known as CDKN2A) mRNA levels) in which D + Q concomitantly increased P1NP (+34%, P = 0.035) and reduced CTx (-11%, P = 0.049) at 2 weeks, and increased radius bone mineral density (+2.7%, P = 0.004) at 20 weeks. Thus, intermittent D + Q treatment did not reduce bone resorption in the overall group of postmenopausal women. However, our exploratory analyses indicate that further studies are needed testing the hypothesis that the underlying senescent cell burden may dictate the clinical response to senolytics. ClinicalTrials.gov identifier: NCT04313634 .
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“serum P1NP increased at 2 weeks in the T3 D + Q group (relative to control, +34%, P = 0.035)”
§ Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial > Results > Exploratory and post hoc analyses
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the p16_variant 5 assay appeared to more effectively identify individuals likely to have a favorable skeletal response to D + Q compared with the p16_variant 1 + 5 assay.”
§ Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial > Results > Exploratory and post hoc analyses
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the secondary endpoint, percentage changes in the bone formation marker procollagen type 1 N-terminal propeptide (P1NP), increased significantly (relative to control) in the D + Q group at both 2 weeks (+16%, P = 0.020) and 4 weeks (+16%, P = 0.024), but was not different from control at 20 weeks”
§ Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial > Abstract
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“baseline SASP factors were generally higher in the T3 group versus the T1/T2 group”
§ Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial > Results > Assessment of SASP factors
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“changes in SASP factors did not differ between the control and D + Q groups”
§ Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial > Results > Assessment of SASP factors
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in humans, senolytics (or at least, D + Q with our monthly dosing regimen) may preferentially stimulate bone formation over inhibiting bone resorption”
§ Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial > Discussion
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“radius BMD at 20 weeks, which increased by 2.7% in response to D + Q relative to control (P = 0.004) in the T3 group”
§ Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial > Results > Exploratory and post hoc analyses
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our study represents the largest (n = 60) RCT of sustained intermittent administration of a senolytic regimen to generally healthy older women.”
§ Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial > Discussion
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“our findings support the hypothesis that the skeletal, and perhaps nonskeletal, response to a senolytic intervention depends on the existing senescent cell burden.”
§ Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial > Discussion
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“intermittent D + Q treatment did not reduce bone resorption in the overall group of postmenopausal women.”
§ Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial > Abstract
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“a Phase 2 trial in postmenopausal women showed limited biomarker changes with subtle or no significant clinical improvements in bone mass37.”
From Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming (2026) · cites this paper as [37]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Intraocular study counted as systemic administration
MinorThe discussion includes the diabetic macular edema study among prior studies of systemic senolytic administration, but the paper earlier describes that treatment as a single intraocular injection.
“Previous studies of systemic administration of senolytics have not included a control group, recruited only a limited number of patients with diabetes-associated chronic kidney disease (n = 9)32, idiopathic pulmonary fibrosis (n = 14)33, dementia (n = 5)11 or diabetic macular edema (n = 8)12”
“a single intraocular administration of another senolytic compound, the BCL-xL inhibitor UBX1325, was safe and improved visual acuity in five of eight patients with diabetic macular edema”
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
Cites a retracted work: 10.1016/j.fitote.2015.09.018
InfoThe cited work was retracted on 2024-12-28 (notice 10.1016/j.fitote.2024.106320), not before this paper was published (2024-07-02).
Cited work 10.1016/j.fitote.2015.09.018 · retracted 2024-12-28 · notice 10.1016/j.fitote.2024.106320 · this paper published 2024-07-02
“D’Andrea, G. Quercetin: a flavonol with multifaceted therapeutic applications? Fitoterapia 106, 256–271 (2015).”
Citations
Cites
1 retracted
RETRACTED: Quercetin: A flavonol with multifaceted therapeutic applications?
D’Andrea, G. (2015) · Fitoterapia · doi:10.1016/j.fitote.2015.09.018 · Cited by 743
RetractedThe serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508 · cited 1×
“Cellular senescence was first described by Hayflick and Moorhead in 1961 as an in vitro phenomenon, whereby normal human fibroblasts stopped proliferating and entered a state of irreversible growth arrest 1 .”
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 1×
“Moreover, the demonstration in old mice that clearing senescent cells using a genetic approach extended health span and lifespan 4,5 generated intense interest in therapeutically targeting senescent cells in humans to prevent or delay age-related comorbidities as a group 6 .”
Self-citationNaturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,876
The Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,584 · cited 2×
“…the translation of these findings to humans was the identification of compounds (‘senolytics’) that targeted survival pathways unique to senescent cells, resulting in their selective killing and beneficial effects in old mice similar to those observed with genetic clearance of senescent cells 7,8 .”
Self-citationClearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4010 · Cited by 1,819 · cited 1×
“…the translation of these findings to humans was the identification of compounds (‘senolytics’) that targeted survival pathways unique to senescent cells, resulting in their selective killing and beneficial effects in old mice similar to those observed with genetic clearance of senescent cells 7,8 .”
Cellular senescence and the senescent secretory phenotype: therapeutic opportunities
Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J., & Kirkland, J. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64098 · Cited by 1,774 · cited 2×
“…are mediated via modulation of sclerostin levels (or possibly other effects on Wnt signaling in bone), the advantage of senolytics would be their potential nonskeletal effects on frailty, metabolic dysfunction and other age-associated morbidities 16 , in addition to their skeletal actions.”
Self-citationDasatinib versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia
Kantarjian, H. M., Shah, N. P., Hochhaus, A., Cortes, J. E., Shah, S. A., Ayala, M., Moiraghi, B., Shen, Z., Mayer, J., Pasqüini, R., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1002315 · Cited by 1,572
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486
Hickson, L. J., Langhi Prata, L. G. P., Bobart, S. A., Evans, T. K., Giorgadze, N., Hashmi, S. K., Herrmann, S. M., Jensen, M. D., Jia, Q., Jordan, K. L., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.08.069 · Cited by 1,383 · cited 1×
“…senolytics have not included a control group, recruited only a limited number of patients with diabetes-associated chronic kidney disease ( n = 9) 32 , idiopathic pulmonary fibrosis ( n = 14) 33 , dementia ( n = 5) 11 or diabetic macular edema ( n = 8) 12 and were focused primarily on safety or…”
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–120 of 120
Beaumont, H., Guest, S., Pathak, S., Premjit, Y., Jones, E., & Ganguly, P. (2026) · Biology · doi:10.3390/biology15161377
“Concurrently, the balance is shifted toward bone loss and increased marrow adiposity due to deregulation of bone remodelling pathways, such as decreased Wnt/ β -catenin signalling (Low-density lipoprotein receptor-related protein 5 (LRP5), SOST and increased mTORC1 activity [83,84].”
The senescence–immune axis as a target for combining immunotherapy and senotherapy
Saez‐Calazans, F., Grün, L. K., Stein, L. E., Barbé‐Tuana, F. M., & Filippi‐Chiela, E. C. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103309
Grycan, M., Zyśk, R., Grycan, G., Jakiel, G., Dudek, A., & Gromadzka, G. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27177521
“The exploratory analysis reported by Farr et al. further suggests that baseline senescent cell burden may determine therapeutic responsiveness, supporting this precision-medicine approach in future senolytic trials [141,148,149].”
Zhu, M., Zhang, J., Fang, H., Cai, K., Wu, Q., Gao, C., Wang, Y., & Chen, J. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1917096
Fang, D., Peng, R., He, Y., Wang, P., Liu, Y., Zhang, P., Gong, W., Shen, H., Liu, H., Yu, R., et al. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04969-z
Yu, M., Wu, Y., Wang, A., Wang, M., Chen, Y., Ren, H., Zhang, Y., Liu, Y., Wang, S., & Fan, X. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1874465
Mitochondrial homeodynamics in ageing: mechanisms, resilience, and interventions
Chmielewski, P. P. (2026) · Biogerontology · doi:10.1007/s10522-026-10506-0 · Cited by 2
“Human trials show that pathways can be engaged in older adults, but organ-specific effects cannot be generalized to whole-body ageing (Farr et al. 2024; Mannick et al. 2021).”
The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation
Chmielewski, P. P., & Strzelec, B. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188080
“No senolytic or senomorphic has yet been shown to slow human aging [114,124].”
InfluentialBone aging: a paradigm of multiscale degeneration and targeted rejuvenation
Li, K., Gao, C., Zhang, T., Wang, C., Geng, X., Wang, X., & Tian, H. (2026) · Bone Research · doi:10.1038/s41413-026-00582-w
Yang, G., Wang, J., Zhang, S., Cheng, Y., Li, Y., 杨旭, Qu, L., Wang, J., Liu, Y., Li, Y., et al. (2026) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2026.101794
Zhang, S., Ma, S., Li, H., Pang, Y., Dai, Y., Liu, X., Zhao, T., Liu, B., & Chen, H. (2026) · Journal of Dermatologic Science and Cosmetic Technology · doi:10.1016/j.jdsct.2026.100196
Mosaid, S. M., Jihad, Y., Pepper, N., Elnemr, M., Marudanayagam, A., & Lee, P. Y. (2026) · Bioengineering · doi:10.3390/bioengineering13091088
“Procollagen type 1 N-terminal propeptide increased by 16% relative to control at two weeks ( p = 0.020) and four weeks ( p = 0.024), but not at 20 weeks ( − 9%, p = 0.149); the largest response in women with the highest senescent-cell burden was exploratory [17].”
InfluentialZhang, L., Yao, Y., & Chen, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1940235
Liu, H., & Lei, B. (2026) · Biogerontology · doi:10.1007/s10522-026-10508-y
“Type 2 diabetes mellitus carries increased fracture risk despite often normal or elevated BMD, pointing to impaired bone quality rather than reduced quantity (Napoli et al. 2017; Yang et al. 2025).”
InfluentialGuo, T.-T., Hong-xin, Z., & Jiang, Q.-D. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1949165
Telomeric autophagy in human health, aging, and diseases
Li, X., & Wu, X. (2026) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2026.1922188
Brooks, H. W., Cusick, N. C., Wu, S., & Farr, J. N. (2026) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2026.102203
Self-citationSimpson, D. J., Crofts, S., Mavrommatis, C., White, T. A., Suwanlikit, Y., Loyva, K., Rocca, W. A., Kantarci, K., Mielke, M. M., Richmond, A., et al. (2026) · medRxiv · doi:10.64898/2026.09.29.26364335
Self-citationKoning, M., Kovynev, A., Fondevila, M. F., Ruhé, E. J. M., Mommersteeg, M. C., Ramakers, C. R. B., Hutten, B. A., Verwer, B. J., Vlug, M. S., Kuiper, T., et al. (2026) · Nature Metabolism · doi:10.1038/s42255-026-01643-4 · Cited by 1
Self-citationHuang, J., Ji, L., Jin, H., Shi, Z., Song, X., Cai, Y., & Tong, X. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103398
Metadata
- Authors
- Farr, J. N., Atkinson, E. J., Achenbach, S. J., Volkman, T. L., Tweed, A. J., Vos, S. J., Ruan, M., Sfeir, J., Drake, M. T., Saul, D., Doolittle, M. L., Bancos, I., Yu, K., Tchkonia, T., LeBrasseur, N. K., Kirkland, J. L., Monroe, D. G., & Khosla, S.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Farr, Joshua N.
- Khosla, Sundeep
- ORCID
- Venue
- Nature Medicine
- Published
- 2024-07-02
- Volume
- 30
- Issue
- 9
- Pages
- 2605-2612
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC11705617
- OpenAlex
- W4400248879
- Semantic Scholar
- 0e53cd07806a2b8dfab4ce0f5781c7d52dcac991
- Cited by
- 127
- References
- 39
- Citations by year
- 2026: 67 · 2025: 55 · 2024: 5
- FWCI
- 35.85
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (R21 AG065868, R01 AG076515, R01 AG055529, R37 AG13925, R33 AG61456, P01 AG062413, R01 AG 062413)
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK128552)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- senolytics, intermittent dosing, dasatinib, quercetin, bone metabolism, postmenopausal women, bone loss, bone resorption, bone formation, C-terminal telopeptide of type I collagen, P1NP, CDKN2A, bone mineral density, aging
- MeSH terms
- Dasatinib, Senotherapeutics, Aged, Bone and Bones, Bone Resorption, Female, Humans, Middle Aged, Peptide Fragments, Peptides, Procollagen, Quercetin, Biomarkers, Bone Density, Cellular Senescence, Postmenopause, Cyclin-Dependent Kinase Inhibitor p16, Collagen Type I
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-25 (prompt extract-v2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
