PPARγ accelerates cellular senescence by inducing p16INK4α expression in human diploid fibroblasts
Open accessAbstract
Peroxisome proliferator-activated receptor γ (PPARγ) plays an important role in the inhibition of cell growth by promoting cell-cycle arrest, and PPARγ activation induces the expression of p16INK4α (CDKN2A), an important cell-cycle inhibitor that can induce senescence. However, the role of PPARγ in cellular senescence is unknown. Here, we show that PPARγ promotes cellular senescence by inducing p16INK4α expression. We found several indications that PPARγ accelerates cellular senescence, including enhanced senescence-associated (SA)-β-galactosidase staining, increased G1 arrest and delayed cell growth in human fibroblasts. Western blotting studies demonstrated that PPARγ activation can upregulate the expression of p16INK4α. PPARγ can bind to the p16 promoter and induce its transcription, and, after treatment with a selective PPARγ agonist, we observed more-robust expression of p16INK4α in senescent cells than in young cells. In addition, our data indicate that phosphorylation of PPARγ decreased with increased cell passage. Our results provide a possible molecular mechanism underlying the regulation of cellular senescence.
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Rosiglitazone can induce senescence and p16Ink4a expression via PPARγ activation.
“rosiglitazone, a drug that can induce cellular senescence and p16Ink4a expression through activation of PPARγ16.”
From Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders (2011) · cites this paper as [16]
The “PPARγ-mediated regulation of p16INK4α expression” section reports that PPARγ overexpression or troglitazone treatment increased p16 protein in human fibroblasts; the RNA-interference section links PPARγ-agonist effects to senescence. The paper’s treatment passages name troglitazone and pioglitazone, not rosiglitazone, so they do not establish the claim for that specific drug. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPPARγ is a key transcription factor mediating p16Ink4a gene activation and BMAd senescence.
“Previous studies revealed that PPARγ is a key transcription factor mediating p16Ink4a gene activation53 and BMAd senescence47.”
From Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis (2025) · cites this paper as [53]
15d-PGJ2 is a PPAR-γ ligand, and PPAR-γ is linked to senescence.
“15d-PGJ2 is a ligand for PPAR-γ (Forman et al., 1995; Kliewer et al., 1995), which is linked to senescence (Gan et al., 2008).”
From Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis (2021) · cites this paper as Gan et al., 2008
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- Authors
- Gan, Q., Huang, J., Zhou, R., Niu, J., Zhu, X., Wang, J., Zhang, Z., & Tong, T.
- Affiliations
- Peking University (CN)
- Corresponding author
- Tong, Tanjun
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2008-07-01
- Volume
- 121
- Issue
- 13
- Pages
- 2235-2245
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2050096162
- Cited by
- 82
- References
- 49
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 4 · 2014: 3 · 2013: 5 · 2012: 5
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (2007CB507400, 30671064)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- PPARγ, cellular senescence, p16INK4a, CDKN2A, human diploid fibroblasts, G1 cell cycle arrest, senescence-associated β-galactosidase, PPARγ phosphorylation, transcriptional regulation, PPARγ agonists, cell growth inhibition
- MeSH terms
- Cell Line, Diploidy, Fibroblasts, Humans, Phosphorylation, Promoter Regions, Genetic, Signal Transduction, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, PPAR gamma
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