Premium
Sarcopenia and hypertrophy in aged skeletal muscle is independent of lifelong muscle stem cell depletion
Author(s) -
Lee Jonah Dan,
Mula Jyothi,
Fry Christopher S,
Kirby Tyler J,
Jackson Janna R,
Beggs Jake A,
Campbell Marilyn S,
Kmiec Tyler E,
DupontVersteegden Esther E,
McCarthy John J,
Peterson Charlotte A
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1150.8
Subject(s) - sarcopenia , muscle hypertrophy , skeletal muscle , myocyte , muscle mass , medicine , stem cell , endocrinology , senescence , biology , microbiology and biotechnology
Unresolved questions in aged muscle involve whether the loss of muscle stem cells, satellite cells, contributes to sarcopenia and impedes hypertrophy of aged muscle. To directly address these questions, we developed the Pax7‐DTA mouse that conditionally and specifically ablates Pax7+ satellite cells following tamoxifen administration (TM). Four month old mice were treated with TM or vehicle and at 5 (young) or 24 (old) months of age were subjected to a synergist ablation (SA; two weeks of overload) or sham surgery. With age, vehicle treated muscles demonstrated a 52% reduction in Pax7+ satellite cells. TM treated muscles showed >;90% ablation after 1 month and no recovery after 20 months, such that the aged mice lived the majority of their lives with a significantly reduced satellite cell pool. Despite Pax7 depletion with TM, muscle mass, fiber cross‐sectional area and function were all reduced with age independent of Pax7 number. After SA, TM mice increased muscle mass and fiber cross‐sectional area to the same extent as vehicle, with old mice demonstrating an attenuated hypertrophy compared to young. Large myofiber distribution decreased with age and increased with SA, independent of Pax7 number. However, the total number of small fibers (<600 um 2 ), relatively more abundant in aged muscle, were reduced with TM. These data provide convincing evidence the satellite cell niche does not play a role in maintenance of skeletal muscle mass across the lifespan or in hypertrophy of young or old muscle. Funding: NIH R01AR060701, R21AG34453. Ellison Foundation/American Federation of Aging Research EPD12102.