Cited by 155Telomeres, Telomerase, and SenescenceCancer-related Molecular PathwaysGenetics, Aging, and Longevity in Model Organisms

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Increased p53 Protein Associated with Aging in Human Diploid Fibroblasts

Kulju, Karen S., Lehman, John M.·1995·Experimental Cell Research

DOI 10.1006/excr.1995.1095

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Abstract

Molecular changes associated with cellular aging in a strain of human diploid fibroblasts, IMR-90, were addressed by analyzing the expression of the tumor suppressor protein, p53. In all studies, IMR-90 cultures were characterized as "young" or "near-senescent" based on morphology, rate of population doubling, capacity for DNA synthesis, and presence of established markers for senescence. When p53 was immunoprecipitated by monoclonal antibodies and detected by Western immunoblot analysis, more protein per cell was detected in the near-senescent cultures. A greater than 10-fold increase in p53 protein was measured with the PAb 1801 (N-terminal-specific) anti-p53 antibody, whereas PAb 122 (C-terminal-specific) measured a 5-fold increase. Although near-senescent cultures demonstrated a higher level of p53 than young cells, these cultures had similar charges and molecular weight p53 isoforms when analyzed by two-dimensional Western blots. When p53 RNA was compared to total RNA there was a decrease in p53 RNA with age, but on a per cell basis p53 RNA was elevated. These results provide evidence for transcriptional regulation of p53 during aging and support the hypothesis that elevated levels of p53 protein may play a role in cellular senescence.

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“…between telomere loss and cell senescence has not been elucidated, it is known that the cell cycle control protein, p53, is located near telomeres (Levine et al. 1993), and other studies have shown a relationship between telomere loss and aging (Kulju & Lehman 1995, Vaziri & Benchimol 1996,…”
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“The p53 protein is stabilized and proceeds to activate its transcriptional targets, such as p21 (Kulju and Lehman, 1995).”
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“In general, the activity of p53 increases in the course of cellular senescence with or without an elevation of p53 expression (Atadja et al., 1995; Kulju and Lehman, 1995).”
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“These modifications contribute to displacement of mdm2 from p53 allowing its stabilization and activation (Kulju & Lehman 1995; Vaziri et al. 1997; Gire et al. 2004; Artandi & Attardi 2005).”
Background

Authors: Kulju, K. S., & Lehman, J. M.
Affiliations: Albany Medical College (US)
ORCID: Lehman, John M.
Venue: Experimental Cell Research
Publisher: Elsevier BV
Published: 1995-04
Volume: 217
Issue: 2
Pages: 336-345
ISSN: 0014-4827 (ISSN-L)
DOI: 10.1006/excr.1995.1095
OpenAlex: W2062636398
Cited by: 155
References: 0
Citations by year: 2026: 1 · 2024: 1 · 2023: 4 · 2022: 2 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 3 · 2012: 8
FWCI: 5.07
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Experimental Cell Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (CA-41608)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: p53, cellular senescence, cellular aging, human diploid fibroblasts, IMR-90 cells, p53 protein levels, p53 isoforms, tumor suppressor proteins
MeSH terms: Cell Cycle, Cell Line, Diploidy, Fibroblasts, Humans, RNA, Messenger, Electrophoresis, Gel, Two-Dimensional, Tumor Suppressor Protein p53, Cellular Senescence

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Increased p53 Protein Associated with Aging in Human Diploid Fibroblasts

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