Lamin B1 loss is a senescence-associated biomarker

Freund, Adam; Laberge, Remi-Martin; Demaria, Marco; Campisi, Judith

doi:10.1091/mbc.e11-10-0884

Lamin B1 loss is a senescence-associated biomarker

Journal Article · Fri Jun 01 00:00:00 EDT 2012 · Molecular Biology of the Cell

DOI:https://doi.org/10.1091/mbc.e11-10-0884· OSTI ID:1625229

Freund, Adam ^[1]; Laberge, Remi-Martin ^[2]; Demaria, Marco ^[2]; Campisi, Judith ^[3]

Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Buck Inst. for Research on Aging, Novato, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); DOE/OSTI
Buck Inst. for Research on Aging, Novato, CA (United States)
Buck Inst. for Research on Aging, Novato, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Cellular senescence is a potent tumor-suppressive mechanism that arrests cell proliferation and has been linked to aging. However, studies of senescence have been impeded by the lack of simple, exclusive biomarkers of the senescent state. Senescent cells develop characteristic morphological changes, which include enlarged and often irregular nuclei and chromatin reorganization. Because alterations to the nuclear lamina can affect both nuclear morphology and gene expression, we examined the nuclear lamina of senescent cells. We show here than lamin B1 is lost from primary human and murine cell strains when they are induced to senesce by DNA damage, replicative exhaustion, or oncogene expression. Lamin B1 loss did not depend on the p38 mitogen-activated protein kinase, nuclear factor-κB, ataxia telangiectasia–mutated kinase, or reactive oxygen species signaling pathways, which are positive regulators of senescent phenotypes. However, activation of either the p53 or pRB tumor suppressor pathway was sufficient to induce lamin B1 loss. Lamin B1 declined at the mRNA level via a decrease in mRNA stability rather than by the caspase-mediated degradation seen during apoptosis. Last, lamin B1 protein and mRNA declined in mouse tissue after senescence was induced by irradiation. Our findings suggest that lamin B1 loss can serve as biomarker of senescence both in culture and in vivo.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1625229

Journal Information:: Molecular Biology of the Cell, Journal Name: Molecular Biology of the Cell Journal Issue: 11 Vol. 23; ISSN 1059-1524

Publisher:: American Society for Cell BiologyCopyright Statement

Country of Publication:: United States

Language:: English

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Additional file 1 of Similarities and differences between rat and mouse chondrocyte gene expression induced by IL-1β Ding, Dao-Fang; Xue, Yan; Zhang, Jun-Peng figshare https://doi.org/10.6084/m9.figshare.19126389.v1	dataset	January 2022
Additional file 2 of Similarities and differences between rat and mouse chondrocyte gene expression induced by IL-1β Ding, Dao-Fang; Xue, Yan; Zhang, Jun-Peng figshare https://doi.org/10.6084/m9.figshare.19126392.v1	dataset	January 2022
Additional file 3 of Similarities and differences between rat and mouse chondrocyte gene expression induced by IL-1β Ding, Dao-Fang; Xue, Yan; Zhang, Jun-Peng figshare https://doi.org/10.6084/m9.figshare.19126395	dataset	January 2022
Additional file 4 of Similarities and differences between rat and mouse chondrocyte gene expression induced by IL-1β Ding, Dao-Fang; Xue, Yan; Zhang, Jun-Peng figshare https://doi.org/10.6084/m9.figshare.19126398.v1	image	January 2022
Additional file 1 of The chromatin accessibility and transcriptomic landscape of the aging mice cochlea and the identification of potential functional super-enhancers in age-related hearing loss Zhang, Chanyuan; Yang, Ting; Luo, Xiaoqin figshare https://doi.org/10.6084/m9.figshare.26182271.v1	dataset	January 2024
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RNA sequencing identifies common pathways between cigarette smoke exposure and replicative senescence in human airway epithelia Jun-Ho, Jang,; K., Mallampalli, Rama; Xiuying, Li, BioMed Central https://doi.org/10.17615/ep0k-ck58	text	January 2019
Short-term gain, long-term pain: the senescence life cycle and cancer. Chan, Adelyne Sue Li; Narita, Masashi Cold Spring Harbor Laboratory https://doi.org/10.17863/cam.35478	journalarticle	January 2019
Aging Triggers H3K27 Trimethylation Hoarding in the Chromatin of Nothobranchius Furzeri Skeletal Muscle Cencioni, Chiara; Heid, Johanna; Keprelova, Anna Cells https://doi.org/10.20944/preprints201908.0032.v1	journal	August 2019
Biomarkers of Cellular Senescence and Skin Aging Wang, Audrey S.; Dreesen, Oliver Frontiers in Genetics, Vol. 9 https://doi.org/10.3389/fgene.2018.00247	journal	August 2018
Genetic Pathways of Aging and Their Relevance in the Dog as a Natural Model of Human Aging Sándor, Sára; Kubinyi, Enikő Frontiers in Genetics, Vol. 10 https://doi.org/10.3389/fgene.2019.00948	journal	October 2019
Role of the Inflammation-Autophagy-Senescence Integrative Network in Osteoarthritis Vinatier, Claire; Domínguez, Eduardo; Guicheux, Jerome Frontiers in Physiology, Vol. 9 https://doi.org/10.3389/fphys.2018.00706	journal	June 2018
Aging Triggers H3K27 Trimethylation Hoarding in the Chromatin of Nothobranchius furzeri Skeletal Muscle Cencioni, Chiara; Heid, Johanna; Krepelova, Anna Cells, Vol. 8, Issue 10 https://doi.org/10.3390/cells8101169	journal	September 2019
Senescent Microvesicles: A Novel Advance in Molecular Mechanisms of Atherosclerotic Calcification Alique, Matilde; Ramírez-Carracedo, Rafael; Bodega, Guillermo International Journal of Molecular Sciences, Vol. 19, Issue 7 https://doi.org/10.3390/ijms19072003	journal	July 2018
Ageing, Cellular Senescence and Neurodegenerative Disease Kritsilis, Marios; V. Rizou, Sophia; Koutsoudaki, Paraskevi International Journal of Molecular Sciences, Vol. 19, Issue 10 https://doi.org/10.3390/ijms19102937	journal	September 2018
Involvement of Lamin B1 Reduction in Accelerated Cellular Senescence during Chronic Obstructive Pulmonary Disease Pathogenesis Saito, Nayuta; Araya, Jun; Ito, Saburo The Journal of Immunology, Vol. 202, Issue 5 https://doi.org/10.4049/jimmunol.1801293	journal	January 2019
Disruption of lamin B1 and lamin B2 processing and localization by farnesyltransferase inhibitors Adam, Stephen A.; Butin-Israeli, Veronika; Cleland, Megan M. Nucleus, Vol. 4, Issue 2 https://doi.org/10.4161/nucl.24089	journal	March 2013
The Role of Cellular Senescence in the Gastrointestinal Mucosa Penfield, Joshua D.; Anderson, Marlys; Lutzke, Lori Gut and Liver, Vol. 7, Issue 3 https://doi.org/10.5009/gnl.2013.7.3.270	journal	May 2013
Chromatin maintenance and dynamics in senescence: a spotlight on SAHF formation and the epigenome of senescent cells Corpet, Armelle; Stucki, Manuel Springer https://doi.org/10.5167/uzh-106116	text	January 2014

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