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Updated: Aug 5, 2026
09:29
Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications
Published on: May 18, 2017
P48: a novel nuclear protein possibly associated with aging and mortality
J L Pipkin1, W G Hinson, L E Lyn-Cook
1Division of Genetic Toxicology, National Center For Toxicological Research, Jefferson, Arkansas 72079-9502, USA.
Aging (Milan, Italy)
|October 1, 1996
Summary
Aging impairs stress protein synthesis, with old rats on ad libitum diets showing reduced stress protein (sp) synthesis and increased mortality after isoproterenol (IPR) administration. Diet restriction in old rats preserved sp synthesis and protected against IPR-induced lethality.
Area of Science:
- Molecular Biology
- Gerontology
- Toxicology
Background:
- Aging is associated with cellular stress responses and altered protein synthesis.
- Diet restriction (DR) is known to influence aging and stress resistance.
- Isoproterenol (IPR) is a chemical inducer used to study stress responses.
Purpose of the Study:
- To investigate the synthesis of stress proteins (SPs) and nuclear protein 48 (p48) in aging rats.
- To compare SP and p48 synthesis in young, old ad libitum (AL), and old diet-restricted (DR) rats.
- To assess the impact of IPR administration on SP/p48 synthesis and survival in different rat groups.
Main Methods:
- Male Fischer 344 rats (young AL, old AL, old DR) were administered IPR.
- Synthesis of stress proteins (SPs: 24, 25, 70, 90 kDa) and nuclear protein 48 (p48) was measured via [35S]-incorporation.
- Cellular localization (heart, bone marrow nuclei) and protein characteristics (isoforms, antigenic response) were analyzed.
Main Results:
- Old AL rats showed significantly reduced SP synthesis in bone marrow and heart nuclei compared to young AL and old DR rats after IPR.
- A unique SP24 was expressed in the heart post-IPR. A lethal IPR dose induced p48 synthesis exclusively in old AL rats.
- p48 expression in old AL rats was cell-cycle regulated and antigenically similar to HL60 cell p48; p48 presence correlated with mortality.
Conclusions:
- Aging, particularly under ad libitum feeding, compromises stress protein synthesis and increases susceptibility to IPR-induced lethality.
- Diet restriction preserves stress protein synthesis and confers protection against IPR toxicity in aged rats.
- Nuclear protein 48 (p48) expression is linked to mortality and ad libitum feeding in old rats, suggesting a role in age-related decline.
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