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CHIP Deficiency Decreases Longevity, with Accelerated Aging Phenotypes Accompanied by Altered Protein Quality Control
Open accessAbstract
During the course of biological aging, there is a gradual accumulation of damaged proteins and a concomitant functional decline in the protein degradation system. Protein quality control is normally ensured by the coordinated actions of molecular chaperones and the protein degradation system that collectively help to maintain protein homeostasis. The carboxyl terminus of Hsp70-interacting protein (CHIP), a ubiquitin ligase/cochaperone, participates in protein quality control by targeting a broad range of chaperone substrates for proteasome degradation via the ubiquitin-proteasome system, demonstrating a broad involvement of CHIP in maintaining cytoplasmic protein quality control. In the present study, we have investigated the influence that protein quality control exerts on the aging process by using CHIP-/- mice. CHIP deficiency in mice leads to a markedly reduced life span, along with accelerated age-related pathophysiological phenotypes. These features were accompanied by indications of accelerated cellular senescence and increased indices of oxidative stress. In addition, CHIP-/- mice exhibit a deregulation of protein quality control, as indicated by elevated levels of toxic oligomer proteins and a decline in proteasome activity. Taken together, these data reveal that impaired protein quality control contributes to cellular senescence and implicates CHIP-dependent quality control mechanisms in the regulation of mammalian longevity in vivo.
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“studies in CHIP defective mice also support an important role for the UPS in longevity and health-span (Min et al., 2008)”
From Protein Homeostasis and Aging: the importance of exquisite quality control (2011) · cites this paper as Min et al., 2008
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“Also, mutant mice deficient in a co-chaperone of the heat-shock family exhibit accelerated-aging phenotypes, whereas long-lived mouse strains show a marked up-regulation of some heat-shock proteins (Min et al., 2008; Swindell et al., 2009).”
From The Hallmarks of Aging (2013) · cites this paper as Min et al., 2008
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Cites
Plum, F. (1960) · Archives of Neurology · doi:10.1001/archneur.1960.03840090124020 · Cited by 10,388
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G. (2003) · Science · doi:10.1126/science.1079469 · Cited by 4,064
Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein
Hartl, F. U., & Hayer-Hartl, M. K. (2002) · Science · doi:10.1126/science.1068408 · Cited by 3,335
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,379
Impairment of the Ubiquitin-Proteasome System by Protein Aggregation
Bence, N., Sampat, R. M., & Kopito, R. R. (2001) · Science · doi:10.1126/science.292.5521.1552 · Cited by 2,209
Protein degradation and protection against misfolded or damaged proteins.
Goldberg, A. L. (2003) · Nature · doi:10.1038/nature02263 · Cited by 2,088
Paffenbarger, R. S., Hyde, R. T., Wing, A. L., Lee, I.-M., Jung, D. L., & Kampert, J. B. (1993) · New England Journal of Medicine · doi:10.1056/nejm199302253280804 · Cited by 1,972
Molecular Chaperones and Protein Quality Control
Bukau, B., Weissman, J. S., & Horwich, A. L. (2006) · Cell · doi:10.1016/j.cell.2006.04.014 · Cited by 1,580
Regulation of aging and age-related disease by DAF-16 and heat-shock factor
Hsu, A.-L., Murphy, C. T., & Kenyon, C. (2003) · Science · doi:10.1126/science.1083701 · Cited by 1,513
Flagged first, then by citations
Research works printed but not linked: 2
- Lakatta E. G., 1987, Geriatrics, 42, 84
- Steinmann G. G., 1986, Curr. Top. Pathol., 75, 43
Cited by
Sorted by citations
Items 201–255 of 255
Martineau, C. N., Dall, M. L., Melki, R., Beckerich, J.-M., & Kabani, M. (2011) · Cell Stress and Chaperones · doi:10.1007/s12192-011-0302-6 · Cited by 3
“…roles in protein quality control, stress resistance, development, and aging in several cellular, animal, or plant models including human cells, mice, Caenorhabditis elegans, and Arabidopsis thaliana (Dai et al. 2003; Khan and Nukina 2004; Yan et al. 2003; Qian et al. 2006; Min et al. 2008).”
BackgroundProteostasis or Aging: Let the CHIPs Fall Where They May
Branicky, R. S., & Hekimi, S. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.04.006 · Cited by 3
Yuan, W., Wang, S., Chen, Y., & Liang, Y. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.151811 · Cited by 2
Autophagy decline during ageing: Molecular regulation, tissue specificity, and therapeutic potential
Goyal, A., Kumari, A., Agrawal, N., & Yadav, H. N. (2026) · Pathology - Research and Practice · doi:10.1016/j.prp.2026.156568 · Cited by 2
Aging: Reading, Reasoning, and Resolving Using Drosophila as a Model System
Nisha, N., Raj, K., Pragati, Tandon, S., Chanu, S. I., & Sarkar, S. (2020) · Springer eBooks · doi:10.1007/978-981-32-9005-1_14 · Cited by 3
Pereira, C. D., Espadas, G., Martins, F., Bertrand, A., Servais, L., Sabidó, E., Chevalier, P., Silva, O. A. B. D. C. E., & Rebelo, S. (2024) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2024.101757 · Cited by 2
“Similarly, the deregulation of the above PQC factors has been linked, for instance, to premature senescence (STUB1) [100], neurodegenerative motor neuron disease (UBA1) [101], myofibrillar myopathy, cardiomyopathy and congenital cataracts ( α B-crystallin) [102].”
BackgroundSchneider, T., Radhakrishnan, Krieger, Dietz, D., Nagel, Bähr, M., & Hescheler (2011) · Journal of Receptor Ligand and Channel Research · doi:10.2147/jrlcr.s19647 · Cited by 2
“CHIP deficiency in mice reduces their lifespan, along with an accelerated agerelated pathophysiological phenotype.(44) Interestingly, CHIP, as well as Hsp70 (Hsp72), interacts with apoptosis signal-regulating kinase 1 (ASK1), and prevents apoptosis.”
BackgroundИльинский, Н. С., Nesterov, S. V., Shestoperova, E. I., Fonin, A. V., Уверский, В. Н., & Gordeliy, V. (2021) · Biochemistry (Moscow) · doi:10.31857/s0320972521030040 · Cited by 2
Chaperone-directed ubiquitylation maintains proteostasis at the expense of longevity
Pokrzywa, W., Lorenz, R., & Hoppe, T. (2017) · Worm · doi:10.1080/21624054.2017.1371403 · Cited by 2
“In agreement with its role in protein quality control, CHIP knockout mice exhibit reduced lifespan associated with age-related pathophysiological defects.(34) Otherwise, CHIP knockout mice exhibit normal embryonic development and unaffected turnover of various CHIP substrates.”
BackgroundBolado‐Carrancio, A., Tapia, O., & Rodríguez-Rey, J. C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168800 · Cited by 2
“Consistent with this, CHIP KO models show age-related muscle loss [159].”
Protein Quality Control Coming of Age
Meiners, S. (2014) · Wiley eBooks · doi:10.1002/9781118396292.ch3 · Cited by 1
Molecular Chaperones as Facilitators of Protein Degradation
Höhfeld, J., Dick, N., & Arndt, V. (2010) · Springer eBooks · doi:10.1007/978-1-4419-7061-9_3
“CHIP deficiency in mice leads to a markedly reduced life span, along with an increased accumulation of toxic protein oligomers ( Min et al. 2008 ).”
BackgroundIdentification and Functional Studies of Arabidopsis thaliana Ubc13-interacting E3 Ubiquitin Ligases
Qian, S. (2012) · University Library - University of Saskatchewan (University of Saskatchewan)
Regulation of integrin-linked kinase (ILK) stability
Radovanac, K. (2012) · Elektronische Hochschulschriften der LMU München (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.16020
Evaluating age-associated phenotypes in a mouse model of protein dyshomeostasis
Min, J.-N., & Patterson, C. (2010) · Methods · doi:10.1016/j.ymeth.2010.12.012
“Mice deficient in CHIP exhibit a shortened life span with a premature aging phenotype accompanied by a decline in protein quality control [12].”
BackgroundMethodInfluentialSelf-citationDamage Segregation and Cellular Rejuvenation in Saccharomyces cerevisiae
Hill, S. M. (2015)
Identification of CHIP as a novel causative gene for autosomal recessive cerebellar ataxia
One, P. L. O. S. (2015)
Thompson, A. C. S. (2014) · ProQuest Demo Repository
Role of C-terminus of HSC70 interacting protein in determining neuronal fate in acute injury
Stankowski, J. N. (2011)
Hui, T. (2013) · National University of Singapore
Kaushik, S., & Cuervo, A. M. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-378638-8.00013-0 · Cited by 1
Proteasomal Degradation of Soluble, Misfolded Proteins
Seneci, P. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800186-8.00003-1
Wadosky, K. M. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/b4hy-4b98
Rakshit, M. (2017) · DR-NTU (Nanyang Technological University) · doi:10.32657/10356/72725
CHIPped balance of proteostasis and longevity
Pokrzywa, W., & Hoppe, T. (2017) · Oncotarget · doi:10.18632/oncotarget.22101
Changes in protein function underlies the disease spectrum in patients with CHIP mutationsPreprint
Madrigal, S. C., McNeil, Z., Sanchez-Hodge, R., Shi, C.-H., Patterson, C., Scaglione, K. M., & Schisler, J. C. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/620591
Self-citationRubel, C. E. (2015) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/ppnw-jz43
Romanucci, M., & Salda, L. D. (2019) · Heat shock proteins · doi:10.1007/978-3-030-24285-5_8
Dias, C., Nita, E., Faktor, J., Hernychová, L., Vojtěšek, B., Nylandsted, J., Hupp, T. R., Kunath, T., & Ball, K. L. (2020) · SSRN Electronic Journal · doi:10.2139/ssrn.3751766
Adaptor protein WDFY3 is neuroprotective by counteracting age-dependent decline in proteostasis
Fun, X. H. (2020) · DR-NTU (Nanyang Technological University) · doi:10.32657/10356/139649
Multi-omic analysis of the aging mouse brain
Kluever, V. (2021) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-9022
Faculty Opinions recommendation of The hallmarks of aging.
Hickson, I. D., & Mankouri, H. W. (2013) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718061760.793481794
A biological perspective of ageing
Guerville, F., & Lemoine, M. (2022) · Wiley eBooks · doi:10.1002/9781119484288.ch1
Age-dependent transcriptional and epigenetic alterations in mouse hepatocytes
Sharma, A. (2021) · DR-NTU (Nanyang Technological University) · doi:10.32657/10356/155390
Macario, A. J. L., de Macario, E. C., & Cappello, F. (2013) · SpringerBriefs in biochemistry and molecular biology · doi:10.1007/978-94-007-4667-1_6
Exploring the role of protein quality control in aging and age-associated neurodegenerative diseases
Gogia, N., Olmos, V., Haidery, F., Luttik, K. P., Tejwani, L., & Lim, J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90235-9.00012-4
Callahan, M. D., Hodul, M., Carroll, E. C., Ravalin, M., Nadel, C. M., Silva, A. R. I. D., Cupo, A. R., McDermott, L. E., Nix, J. C., Page, R. C., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.17.549407
Younger, D. S. (2023) · Handbook of clinical neurology · doi:10.1016/b978-0-323-98818-6.00003-0
The role of E3 ubiquitin ligases in vertebrate eye development: Mechanisms and emerging perspectives
Li, X., Xu, Y., & Zhang, J. (2025) · Experimental Eye Research · doi:10.1016/j.exer.2025.110702
Altınok, S., Paulаkonis, E., de Almeida, M. F., Hwang, I. W., Sanchez‐Hodge, R., D’Ovidio, C., Roper, G., Irons, G., Vargas, E., Peng, I.-W., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.26.690709
Malyshev, I. Y. (2013) · SpringerBriefs in biochemistry and molecular biology · doi:10.1007/978-94-007-5943-5_7
Teissier, T. (2019) · theses.fr (ABES) · doi:10.70675/f49bc069z5ee6z4c49zb46fz0a1413dbba95
Implication du gène Dicer1 dans le vieillissement et ses pathologies chez la souris
de Cauwer, A. (2020) · theses.fr (ABES) · doi:10.70675/22c08094z1342z429fza3fez5ff6b78d1481
The nuclear protein quality control system for the elimination of stress-induced aggregates
Brunello, L. (2021) · theses.fr (ABES) · doi:10.70675/ce9204b1z17c7z476bz9bd5z4e801e0613ef
Inflammation, aging and chronic diseases : implication of inflammasomes
Guerville, F. (2023) · theses.fr (ABES) · doi:10.70675/eac3286czda71z4606z9c90z3d3efeaf1afe
Altınok, S., Paulаkonis, E., de Almeida, M. F., Hwang, I. W., Sanchez‐Hodge, R., D’Ovidio, C., Eidman, A. S., Shrestha, S., Roper, G., Irons, G., et al. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.113399
“This region, crucial for dimerization (25, 43, 44), may be highly intolerant to alterations, as disruptions could completely abolish CHIP function and potentially cause embryonic death or non-viable phenotypes, similar to homozygous Stub1 knockout mice that die perinatally (31, 45).”
E3 Ubiquitin ligases molecular strategies against proteostasis defects of imperfect ageing
Upadhyay, A., Joshi, V., Amanullah, A., Mishra, R., Verma, R. K., Adlakha, Y. K., Suresh, A. K., Dhiman, R., Bhattacharyya, S., & Mishra, A. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103319
Dabur, R. (2026) · Cell Biochemistry and Function · doi:10.1002/cbf.70297
Mouraux, C., Méreaux, J., Davoine, C.-S., Guillot‐Noël, L., Petit, E., Thomas, Q., Nasraoui, A., Heinzmann, A., Ewenczyk, C., Brice, A., et al. (2026) · Movement Disorders · doi:10.1002/mds.70534
Yakubu, R. (2026) · Advances in experimental medicine and biology · doi:10.1007/978-3-032-29437-1_28
Cellular Senescence and Premature Aging in Lung Diseases
Aoshiba, K., Tsuji, T., Yamaguchi, K., Itoh, M., & Nakamura, H. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-397803-5.00017-4
Protein Quality Control in Cardiomyocytes
Wang, X., & Patterson, C. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-381510-1.00027-2
Self-citation
Metadata
- Authors
- Min, J.-N., Whaley, R. A., Sharpless, N. E., Lockyer, P., Portbury, A. L., & Patterson, C.
- Affiliations
- Carolina Cardiovascular Biology Center
- UNC Lineberger Comprehensive Cancer Center (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Patterson, Cam
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2008-06-01
- Volume
- 28
- Issue
- 12
- Pages
- 4018-4025
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC2423116
- OpenAlex
- W2143659623
- Cited by
- 256
- References
- 49
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 5 · 2023: 12 · 2022: 8 · 2021: 16 · 2020: 20 · 2019: 14 · 2018: 18 · 2017: 19 · 2016: 17 · 2015: 11 · 2014: 22 · 2013: 19 · 2012: 14
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- American Heart Association
- National Institutes of Health (5r01gm061728-12)
- National Institute on Aging (AG 024282, P01 AG 024282)
- National Heart, Lung, and Blood Institute (HL 65619, R01HL065619, R37HL065619)
- National Institute of General Medical Sciences (GM-61728, R01-GM061728)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- CHIP, protein quality control, aging, longevity, accelerated aging, cellular senescence, proteasome activity, ubiquitin-proteasome system, oxidative stress, protein aggregation, proteostasis
- MeSH terms
- Aging, Animals, Brain, Cytoplasm, Lipids, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Oxygen, Phenotype, Cellular Senescence, Molecular Chaperones, Ubiquitin-Protein Ligases, Proteasome Endopeptidase Complex, Mice
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