NAITO Atsuhiko, KOMURO Issei ≪Department of Cardiovascular Regenerative Medicine・Cardiovascular Medicine≫ “Complement C1q Activates Canonical Wnt Signaling and Promotes Aging-Related Phenotypes”

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PublishCell, 149(6): 1298-1313 (2012)

Wnt signaling and affect diverse cellular responses during development. Wnt signaling also plays critical roles in various physiological and pathological processes in adult organisms including stem cell self-renewal/differentiation, degenerative diseases, and carcinogenesis. Recent studies have revealed a novel role of Wnt signaling in the regulation of mammalian aging. Wnt/β-catenin signaling is augmented in a mouse model of accelerated aging, and inhibition of canonical Wnt signaling reverses the aging-associated impairment of skeletal muscle regeneration. In the present study, we identified that complement C1q is the nature of a factor that activates Wnt signaling and induces aging-associated impairment of muscle regeneration. C1q binds to Fz receptors and activates canonical Wnt signaling by inducing C1s-dependent cleavage of the ectodomain of LRP6. C1q concentration in the serum is increased with aging, which was associated with increased Wnt signaling activity in serum and Wnt target gene expression in multiple tissues during aging. We also show that C1q-triggerd activation of Wnt signaling accounts for the impaired regenerative capacity of skeletal muscle regeneration in aged mice. These results suggest the novel role of C1q in Wnt signaling activation and mammalian aging.