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#Post#: 1495--------------------------------------------------
Effects of IGF1 Isoforms on Muscle Growth
By: Road2HardCoreIron Date: November 13, 2022, 4:37 pm
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Aging Cell
. 2019 Jun;18(3):e12954. doi: 10.1111/acel.12954. Epub 2019 Apr
5.
Effects of IGF-1 isoforms on muscle growth and sarcopenia
Francesca Ascenzi 1, Laura Barberi 1, Gabriella Dobrowolny 1,
Aline Villa Nova Bacurau 2, Carmine Nicoletti 1, Emanuele
Rizzuto 3, Nadia Rosenthal 4 5, Bianca Maria Scicchitano 6,
Antonio Musaṛ 1
Affiliations expand
PMID: 30953403 PMCID: PMC6516183 DOI: 10.1111/acel.12954
Free PMC article
Abstract
The decline in skeletal muscle mass and strength occurring in
aging, referred as sarcopenia, is the result of many factors
including an imbalance between protein synthesis and
degradation, changes in metabolic/hormonal status, and in
circulating levels of inflammatory mediators. Thus, factors that
increase muscle mass and promote anabolic pathways might be of
therapeutic benefit to counteract sarcopenia. Among these, the
insulin-like growth factor-1 (IGF-1) has been implicated in many
anabolic pathways in skeletal muscle. IGF-1 exists in different
isoforms that might exert different role in skeletal muscle.
Here we study the effects of two full propeptides IGF-1Ea and
IGF-1Eb in skeletal muscle, with the aim to define whether and
through which mechanisms their overexpression impacts muscle
aging. We report that only IGF-1Ea expression promotes a
pronounced hypertrophic phenotype in young mice, which is
maintained in aged mice. Nevertheless, examination of aged
transgenic mice revealed that the local expression of either
IGF-1Ea or IGF-1Eb transgenes was protective against age-related
loss of muscle mass and force. At molecular level, both isoforms
activate the autophagy/lysosome system, normally altered during
aging, and increase PGC1-α expression, modulating
mitochondrial function, ROS detoxification, and the basal
inflammatory state occurring at old age. Moreover, morphological
integrity of neuromuscular junctions was maintained and
preserved in both MLC/IGF-1Ea and MLC/IGF-1Eb mice during aging.
These data suggest that IGF-1 is a promising therapeutic agent
in staving off advancing muscle weakness.
Keywords: IGF-1; NMJ; aging; autophagy; sarcopenia; skeletal
muscle.
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