Research Paper|Volume 15, Issue 11|pp 4685—4698

LAMP2A, and other chaperone-mediated autophagy related proteins, do not decline with age in genetically heterogeneous UM-HET3 mice

Katherine K. Zhang¹, Peichuan Zhang^2,³, Anagha Kodur¹, Ilkim Erturk⁴, Calvin M. Burns⁴, Cynthia Kenyon², Richard A. Miller^4,⁵, S. Joseph Endicott^4,⁵

¹University of Michigan, College of Literature, Science, and The Arts, Ann Arbor, MI 48109, USA
²Calico Life Sciences, South San Francisco, CA 94080, USA
³Current Affiliation: WuXi AppTec, Shanghai, China
⁴University of Michigan, Department of Pathology, Ann Arbor, MI 48109, USA
⁵University of Michigan Geriatrics Center, Ann Arbor, MI 48109, USA

Received: April 21, 2023Accepted: May 30, 2023Published: June 13, 2023

https://doi.org/10.18632/aging.204796

Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Chaperone-mediated autophagy (CMA) selectively degrades proteins that are crucial for glycolysis, fatty acid metabolism, and the progression of several age-associated diseases. Several previous studies, each of which evaluated males of a single inbred mouse or rat strain, have reported that CMA declines with age in many tissues, attributed to an age-related loss of LAMP2A, the primary and indispensable component of the CMA translocation complex. This has led to a paradigm in the field of CMA research, stating that the age-associated decline in LAMP2A in turn decreases CMA, contributing to the pathogenesis of late-life disease. We assessed LAMP2A levels and CMA substrate uptake in both sexes of the genetically heterogeneous UM-HET3 mouse stock, which is the current global standard for the evaluation of anti-aging interventions. We found no evidence for age-related changes in LAMP2A levels, CMA substrate uptake, or whole liver levels of CMA degradation targets, despite identifying sex differences in CMA.