Complement C1q Activates Canonical Wnt Signaling and Promotes Aging-Related Phenotypes
Open accessAbstract
Wnt signaling plays critical roles in development of various organs and pathogenesis of many diseases, and augmented Wnt signaling has recently been implicated in mammalian aging and aging-related phenotypes. We here report that complement C1q activates canonical Wnt signaling and promotes aging-associated decline in tissue regeneration. Serum C1q concentration is increased with aging, and Wnt signaling activity is augmented during aging in the serum and in multiple tissues of wild-type mice, but not in those of C1qa-deficient mice. C1q activates canonical Wnt signaling by binding to Frizzled receptors and subsequently inducing C1s-dependent cleavage of the ectodomain of Wnt coreceptor low-density lipoprotein receptor-related protein 6. Skeletal muscle regeneration in young mice is inhibited by exogenous C1q treatment, whereas aging-associated impairment of muscle regeneration is restored by C1s inhibition or C1qa gene disruption. Our findings therefore suggest the unexpected role of complement C1q in Wnt signal transduction and modulation of mammalian aging.
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The benefits of GPLD1 and other exerkines on brain structure and function may relate to peripheral effects such as complement signalling or coagulation.
“Hence, the benefit of GPLD1 (REF.148) and other exerkines on brain structure and function might relate to its peripheral effects, such as the complement signalling cascade149,158, or coagulation159.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [158]
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- Authors
- Naito, A. T., Sumida, T., Nomura, S., Liu, M.-L., Higo, T., Nakagawa, A., Okada, K., Sakai, T., Hashimoto, A., Hara, Y., Shimizu, I., Zhu, W., Toko, H., Katada, A., Akazawa, H., Oka, T., Lee, J.-K., Minamino, T., Nagai, T., Walsh, K., Kikuchi, A., Matsumoto, M., Botto, M., Shiojima, I., & Komuro, I.
- Affiliations
- Japan Science and Technology Agency (JP)
- Chiba University (JP)
- The University of Osaka (JP)
- Boston University (US)
- Hokkaido University (JP)
- Imperial College London (GB)
- Corresponding author
- Komuro, Issei
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 149
- Issue
- 6
- Pages
- 1298-1313
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3529917
- OpenAlex
- W2160766576
- Cited by
- 320
- References
- 46
- Citations by year
- 2026: 19 · 2025: 20 · 2024: 16 · 2023: 24 · 2022: 32 · 2021: 23 · 2020: 29 · 2019: 23 · 2018: 24 · 2017: 25 · 2016: 22 · 2015: 23 · 2014: 16 · 2013: 15 · 2012: 9
- FWCI
- 8.11
- Type
- journal article
- Language
- en
- Update notices
- erratum (2012-08-03)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Japan Prize Foundation
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Science and Technology Agency
- Japan Foundation for Applied Enzymology
- Japan Society for the Promotion of Science
- Ministry of Health, Labour and Welfare
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- C1q, Wnt/β-catenin signaling, aging, tissue regeneration, Frizzled receptors, skeletal muscle regeneration
- MeSH terms
- Aging, Animals, Complement C1s, Humans, Complement C1q, Serum, Mice, Wnt Signaling Pathway, Low Density Lipoprotein Receptor-Related Protein-6
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