Cited by 65Telomeres, Telomerase, and SenescenceProtease and Inhibitor MechanismsGenetics, Aging, and Longevity in Model Organisms

Overexpression of plasminogen activator inhibitor type‐1 in senescent fibroblasts from normal subjects and those with Werner syndrome

Goldstein, Samuel, Moerman, Elena J., Fujii, Satoshi, Sobel, Burton E.·1994·Journal of Cellular Physiology

Abstract

We previously reported that plasminogen activator inhibitor type‐1 (PAI‐1) mRNA was present at higher steady‐state levels in prematurely senescent fibroblasts derived from a subject with Werner syndrome (WS) compared to early passage (EP) fibroblasts from an age‐matched normal subject (Murano et al., 1991, Mol. Cell. Biol. 11:3905–3914). To explore the generality of this phenomenon with respect to chronological age of donor (in vivo aging) and the late‐passage (LP) or senescent phase of the fibroblast replicative lifespan, we assayed PAI‐1 mRNA in cells and PAI‐1 antigen in medium conditioned by 20 normal fibroblast strains at EP and LP and six WS strains during their curtailed replicative lifespans. The lowest accumulations of PAI‐1 were found in medium conditioned by fetal and newborn cells with a shallow but progressive rise seen in postnatal cells from normal donors of increasing chronological age. With few exceptions, normal LP fibroblasts showed increased PAI‐1 accumulations in medium compared to their EP counterparts. Conditioned medium from four of the six WS strains showed PAI‐1 accumulations that were significantly higher than the media of any normal controls at EP and LP. PAI‐1 mRNA levels were generally commensurate with the cumulative amount of PAI‐1 in the medium but the frequent exceptions indicate that translational and post‐translational mechanisms also regulate PAI‐1 output. The augmentation in PAI‐1 output of fibroblasts as a direct function of chronological age and during in vitro senescence suggests that PAI‐1 may play an important role in the reduced capacity for wound healing and the increasing tendency to thrombogenesis and atherogenesis seen during biological aging and in particular in persons with Werner syndrome. © 1994 Wiley‐Liss, Inc.

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Crossref · 10.1002/jcp.1041610321

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  • Late passage human fibroblasts or fibroblasts from subjects with premature aging syndromes produce secretory proteins including PAI-1, which later became a functional marker of senescence.

    “Early studies showed that late passage human fibroblasts or fibroblasts derived from subjects with premature aging syndromes produce secretory proteins, including plasminogen activator inhibitor type-1 (PAI-1), which later became a functional marker of senescence (Murano et al. 1991; Goldstein et al. 1994; Kortlever et al. 2006).”

    From Cellular senescence and its effector programs (2014) · cites this paper as Goldstein et al. 1994

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Authors
Goldstein, S., Moerman, E. J., Fujii, S., & Sobel, B. E.
Affiliations
  • John L. McClellan Memorial Veterans Hospital (US)
  • Washington University in St. Louis (US)
Corresponding author
Moerman, Elena J.
Venue
Journal of Cellular Physiology
Publisher
Wiley
Published
1994-12
Volume
161
Issue
3
Pages
571-579
ISSN
  • 0021-9541 (ISSN-L)
  • 1097-4652
OpenAlex
W2007249001
Cited by
59
References
31
Citations by year
2026: 1 · 2025: 1 · 2024: 6 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2015: 3 · 2014: 3 · 2012: 1
FWCI
2.72
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Cellular Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ag008708-05)
  • National Institute on Aging (AG08708)
  • National Heart, Lung, and Blood Institute (HL-17646)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
plasminogen activator inhibitor-1, Werner syndrome, premature senescence, fibroblasts, replicative lifespan, in vivo aging, PAI-1 mRNA expression, conditioned medium, translational regulation, post-translational regulation, thrombus formation, atherogenesis, wound healing
MeSH terms
Adult, Aged, Child, Fibroblasts, Humans, Infant, Newborn, Middle Aged, RNA, Messenger, Werner Syndrome, Gene Expression, Cellular Senescence, Plasminogen Activator Inhibitor 1

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