ORIGINAL RESEARCH article
Front. Aging
Sec. Molecular Mechanisms of Aging
This article is part of the Research TopicInsights in Molecular Mechanisms of Aging 2024/2025View all 3 articles
Calreticulin and ERp57 Reduction with Age Reveals the ER Stress-related roles in Cell Viability and Organismal Lifespan Regulation
Provisionally accepted
Gregor Burdeos1,2*
Sophie Neuber- Schlicht1,3- 1Max-Planck-Institut fur Biologie des Alterns, Cologne, Germany
- 2Forschungsinstitut fur Nutztierbiologie (FBN), Dummerstorf, Germany
- 3Department of Chemistry Bioorganic Synthesis, Humboldt-Universitat zu Berlin Mathematisch Naturwissenschaftliche Fakultat, Berlin, Germany
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Defects in Calreticulin (Calr) and ERp57, two tandem endoplasmic reticulum (ER) resident proteins, are associated with pathologies ranging from protein conformational disorders to impaired immune responses but are not directly linked to aging. Here, we report that Calr and ERp57 expression is ubiquitously decreased with age in mouse tissues, and RNAi inhibition of Calr and/or ERp57 homologs in C. elegans led to ER stress-related lifespan shortening. Knockdown of Calr and/or ERp57 in N2a cells reduced cellular viability by exacerbating protein aggregation, ER stress, and activation of pro-apoptotic pathways. Overexpression of Calr and/or ERp57 in N2a cells, however, resulted in a robust increase in cell stress tolerance, cell viability, and inhibition of apoptotic signaling pathways. Taken together, our findings suggest that the age-related reduction of Calr and ERp57 may serve as a potential pro-aging biomarker, contributing to the disruption of ER homeostasis and affecting cell survival and organismal lifespan.
Keywords: Aging, chaperons, Endoplasmic Reticulum, er stress, Protein Folding
Received: 01 Dec 2025; Accepted: 15 Jan 2026.
Copyright: © 2026 Burdeos and Neuber- Schlicht. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Gregor Burdeos
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