PMID- 37315291 OWN - NLM STAT- MEDLINE DCOM- 20230627 LR - 20230701 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 15 IP - 11 DP - 2023 Jun 13 TI - LAMP2A, and other chaperone-mediated autophagy related proteins, do not decline with age in genetically heterogeneous UM-HET3 mice. PG - 4685-4698 LID - 10.18632/aging.204796 [doi] AB - 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. FAU - Zhang, Katherine K AU - Zhang KK AD - University of Michigan, College of Literature, Science, and The Arts, Ann Arbor, MI 48109, USA. FAU - Zhang, Peichuan AU - Zhang P AD - Calico Life Sciences, South San Francisco, CA 94080, USA. AD - Current Affiliation: WuXi AppTec, Shanghai, China. FAU - Kodur, Anagha AU - Kodur A AD - University of Michigan, College of Literature, Science, and The Arts, Ann Arbor, MI 48109, USA. FAU - Erturk, Ilkim AU - Erturk I AD - University of Michigan, Department of Pathology, Ann Arbor, MI 48109, USA. FAU - Burns, Calvin M AU - Burns CM AD - University of Michigan, Department of Pathology, Ann Arbor, MI 48109, USA. FAU - Kenyon, Cynthia AU - Kenyon C AD - Calico Life Sciences, South San Francisco, CA 94080, USA. FAU - Miller, Richard A AU - Miller RA AD - University of Michigan, Department of Pathology, Ann Arbor, MI 48109, USA. AD - University of Michigan Geriatrics Center, Ann Arbor, MI 48109, USA. FAU - Endicott, S Joseph AU - Endicott SJ AD - University of Michigan, Department of Pathology, Ann Arbor, MI 48109, USA. AD - University of Michigan Geriatrics Center, Ann Arbor, MI 48109, USA. LA - eng GR - P30 AG024824/AG/NIA NIH HHS/United States GR - U19 AG023122/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230613 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - 0 (Autophagy-Related Proteins) RN - 0 (Molecular Chaperones) RN - 0 (Lysosomal-Associated Membrane Protein 2) SB - IM MH - Animals MH - Female MH - Male MH - Mice MH - Rats MH - Aging/genetics MH - Autophagy/genetics MH - Autophagy-Related Proteins/metabolism MH - *Chaperone-Mediated Autophagy/genetics MH - Lysosomes/metabolism MH - Molecular Chaperones/genetics/metabolism MH - Lysosomal-Associated Membrane Protein 2/metabolism PMC - PMC10292871 OTO - NOTNLM OT - aging OT - autophagy OT - chaperone-mediated autophagy COIS- CONFLICTS OF INTEREST: The authors have no conflicts of interest to disclose. EDAT- 2023/06/14 19:10 MHDA- 2023/06/22 06:42 PMCR- 2023/06/15 CRDT- 2023/06/14 16:13 PHST- 2023/04/21 00:00 [received] PHST- 2023/05/30 00:00 [accepted] PHST- 2023/06/22 06:42 [medline] PHST- 2023/06/14 19:10 [pubmed] PHST- 2023/06/14 16:13 [entrez] PHST- 2023/06/15 00:00 [pmc-release] AID - 204796 [pii] AID - 10.18632/aging.204796 [doi] PST - ppublish SO - Aging (Albany NY). 2023 Jun 13;15(11):4685-4698. doi: 10.18632/aging.204796. Epub 2023 Jun 13.