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Chronic AICAR treatment enhances anabolic signaling in sarcopenic skeletal muscle
Author(s) -
Calixto Jouber,
Johnson Connor,
Smith Andrew,
Brodowski Kole,
Wilcox Shalene H.,
Hill Jonathon T.,
Thomson David M.
Publication year - 2022
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.2022.36.s1.r5697
Subject(s) - anabolism , mtorc1 , ampk , endocrinology , skeletal muscle , medicine , amp activated protein kinase , chemistry , muscle atrophy , protein kinase a , wasting , sarcopenia , phosphorylation , protein kinase b , biochemistry
Many fields of study have grappled with the challenge of decelerating the effects of aging. Physical exercise plays a vital role in attenuating the impact of the aging process. While many exercise‐induced chemical signaling pathways are not fully understood, AMP‐activated protein kinase mediates many beneficial adaptations to exercise training. AMPK is activated by the accumulation of AMP (and ADP) during muscle contraction‐induced ATP breakdown. The prodrug AICAR mimics AMP accumulation and leads to AMPK activation by increasing the concentration of the AMP analog, ZMP. The primary purpose of the present study is to determine the effect of chronic (31 days) AICAR treatment on muscle anabolic signaling in old (24 mo.) mice. AICAR improved treadmill running performance and attenuated muscle atrophy in the aged mice. Surprisingly, given AICAR's known acute effects on anabolic signaling, AICAR treatment increased the skeletal muscle concentrations of insulin‐like growth factor‐1 and apelin, both of which are known to activate anabolic signaling through the mechanistic target of rapamycin complex 1 (mTORC1). Accordingly, ribosomal protein S6 phosphorylation was also elevated in AICAR‐treated muscles. Our results suggest that in addition to its other well‐established metabolic effects, chronic AICAR treatment may enhance anabolism in sarcopenic muscle and potentially in other muscle‐wasting conditions.