Aging Disrupts Muscle Stem Cell Function by Impairing Matricellular WISP1 Secretion from Fibro-Adipogenic Progenitors

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Jan 29

PMID 30686765

Citations 141

Authors

Laura Lukjanenko

Sonia Karaz

Pascal Stuelsatz

Uxia Gurriaran-Rodriguez

Joris Michaud

Gabriele Dammone

Federico Sizzano

Omid Mashinchian

Sara Ancel

Eugenia Migliavacca

Sophie Liot

Guillaume Jacot

Sylviane Metairon

Frederic Raymond

Patrick Descombes

Alessio Palini

Benedicte Chazaud

Michael A Rudnicki

C Florian Bentzinger

Jerome N Feige

Affiliations

Soon will be listed here.

Abstract

Research on age-related regenerative failure of skeletal muscle has extensively focused on the phenotypes of muscle stem cells (MuSCs). In contrast, the impact of aging on regulatory cells in the MuSC niche remains largely unexplored. Here, we demonstrate that aging impairs the function of mouse fibro-adipogenic progenitors (FAPs) and thereby indirectly affects the myogenic potential of MuSCs. Using transcriptomic profiling, we identify WNT1 Inducible Signaling Pathway Protein 1 (WISP1) as a FAP-derived matricellular signal that is lost during aging. WISP1 is required for efficient muscle regeneration and controls the expansion and asymmetric commitment of MuSCs through Akt signaling. Transplantation of young FAPs or systemic treatment with WISP1 restores the myogenic capacity of MuSCs in aged mice and rescues skeletal muscle regeneration. Our work establishes that loss of WISP1 from FAPs contributes to MuSC dysfunction in aged skeletal muscles and demonstrates that this mechanism can be targeted to rejuvenate myogenesis.

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