ArticlePloS one2016
Temsirolimus Partially Rescues the Hutchinson-Gilford Progeria Cellular Phenotype.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Cancer and aging: complex associations and therapeutic targets.Molecular biomedicine · 2026Review
- Involvement of NRF2 and AMPK signaling in aging and progeria: a digest.Redox biology · 2025Review
- Impact of miR-181a on SIRT1 Expression and Senescence in Hutchinson-Gilford Progeria Syndrome.Diseases (Basel, Switzerland) · 2025Article
- p300 nucleocytoplasmic shuttling underlies mTORC1 hyperactivation in Hutchinson-Gilford progeria syndrome.Nature cell biology · 2024Article
- Lonafarnib and everolimus reduce pathology in iPSC-derived tissue engineered blood vessel model of Hutchinson-Gilford Progeria Syndrome.Scientific reports · 2023Article
- Impact of MnTBAP and Baricitinib Treatment on Hutchinson-Gilford Progeria Fibroblasts.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Article
- Preclinical Advances of Therapies for Laminopathies.Journal of clinical medicine · 2021Review
- Baricitinib, a JAK-STAT Inhibitor, Reduces the Cellular Toxicity of the Farnesyltransferase Inhibitor Lonafarnib in Progeria Cells.International journal of molecular sciences · 2021Article
- Article
- Still Living Better through Chemistry: An Update on Caloric Restriction and Caloric Restriction Mimetics as Tools to Promote Health and Lifespan.International journal of molecular sciences · 2020Review
- Progress and trends in the development of therapies for Hutchinson-Gilford progeria syndrome.Aging cell · 2020Review
- Pharmacotherapy to gene editing: potential therapeutic approaches for Hutchinson-Gilford progeria syndrome.GeroScience · 2020Review
- Review
- Presence and distribution of progerin in HGPS cells is ameliorated by drugs that impact on the mevalonate and mTOR pathways.Biogerontology · 2019Article
- The Cutting Edge: The Role of mTOR Signaling in Laminopathies.International journal of molecular sciences · 2019Review
- Farnesyltransferase inhibitor and rapamycin correct aberrant genome organisation and decrease DNA damage respectively, in Hutchinson-Gilford progeria syndrome fibroblasts.Biogerontology · 2018Article
- Article
- A Novel Generalized Lipodystrophy-Associated Progeroid Syndrome Due to Recurrent Heterozygous LMNA p.T10I Mutation.The Journal of clinical endocrinology and metabolism · 2018Article
- Therapeutic Effect of Repurposed Temsirolimus in Lung Adenocarcinoma Model.Frontiers in pharmacology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hutchinson-Gilford syndrome (HGPS, OMIM 176670, a rare premature aging disorder that leads to death at an average age of 14.7 years due to myocardial infarction or stroke, is caused by mutations in the LMNA gene. Lamins help maintain the shape and stability of the nuclear envelope in addition to regulating DNA replication, DNA transcription, proliferation and differentiation. The LMNA mutation results in the deletion of 50 amino acids from the carboxy-terminal region of prelamin A, producing the truncated, farnesylated protein progerin. The accumulation of progerin in HGPS nuclei causes numerous morphological and functional changes that lead to premature cellular senescence. Attempts to reverse this HGPS phenotype have identified rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), as a drug that is able to rescue the HGPS cellular phenotype by promoting autophagy and reducing progerin accumulation. Rapamycin is an obvious candidate for the treatment of HGPS disease but is difficult to utilize clinically. To further assess rapamycin's efficacy with regard to proteostasis, mitochondrial function and the degree of DNA damage, we tested temsirolimus, a rapamycin analog with a more favorable pharmacokinetic profile than rapamycin. We report that temsirolimus decreases progerin levels, increases proliferation, reduces misshapen nuclei, and partially ameliorates DNA damage, but does not improve proteasome activity or mitochondrial dysfunction. Our findings suggest that future therapeutic strategies should identify new drug combinations and treatment regimens that target all the dysfunctional hallmarks that characterize HGPS cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.