Complement C1q Activates Canonical Wnt Signaling and Promotes Aging-Related Phenotypes | Zendy

Atsuhiko T. Naito | Zendy; Tomokazu S. Sumida | Zendy; Seitaro Nomura | Zendy; MeiLan Liu | Zendy; Tomoaki Higo | Zendy; Akito Nakagawa | Zendy; Katsuki Okada | Zendy; Taku Sakai | Zendy; Akihito Hashimoto | Zendy; Yurina Hara | Zendy; Ippei Shimizu | Zendy; Weidong Zhu | Zendy; Haruhiro Toko | Zendy; Akemi Katada | Zendy; Hiroshi Akazawa | Zendy; Toru Oka | Zendy; JongKook Lee | Zendy; Tohru Minamino | Zendy; Toshio Nagai | Zendy; Kenneth Walsh | Zendy; Akira Kikuchi | Zendy; Misako Matsumoto | Zendy; Marina Botto | Zendy; Ichiro Shiojima | Zendy; Issei Komuro | Zendy

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Complement C1q Activates Canonical Wnt Signaling and Promotes Aging-Related Phenotypes

Author(s) -

Atsuhiko T. Naito,

Tomokazu S. Sumida,

Seitaro Nomura,

MeiLan Liu,

Tomoaki Higo,

Akito Nakagawa,

Katsuki Okada,

Taku Sakai,

Akihito Hashimoto,

Yurina Hara,

Ippei Shimizu,

Weidong Zhu,

Haruhiro Toko,

Akemi Katada,

Hiroshi Akazawa,

Toru Oka,

JongKook Lee,

Tohru Minamino,

Toshio Nagai,

Kenneth Walsh,

Akira Kikuchi,

Misako Matsumoto,

Marina Botto,

Ichiro Shiojima,

Issei Komuro

Publication year - 2012

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2012.03.047

Subject(s) - wnt signaling pathway , biology , frizzled , microbiology and biotechnology , lrp5 , phenotype , signal transduction , lrp6 , ectodomain , regeneration (biology) , receptor , genetics , gene

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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