[PDF][PDF] GDF11 increases with age and inhibits skeletal muscle regeneration
MA Egerman, SM Cadena, JA Gilbert, A Meyer… - Cell metabolism, 2015 - cell.com
MA Egerman, SM Cadena, JA Gilbert, A Meyer, HN Nelson, SE Swalley, C Mallozzi…
Cell metabolism, 2015•cell.comAge-related frailty may be due to decreased skeletal muscle regeneration. The role of TGF-β
molecules myostatin and GDF11 in regeneration is unclear. Recent studies showed an age-
related decrease in GDF11 and that GDF11 treatment improves muscle regeneration, which
were contrary to prior studies. We now show that these recent claims are not reproducible
and the reagents previously used to detect GDF11 are not GDF11 specific. We develop a
GDF11-specific immunoassay and show a trend toward increased GDF11 levels in sera of …
molecules myostatin and GDF11 in regeneration is unclear. Recent studies showed an age-
related decrease in GDF11 and that GDF11 treatment improves muscle regeneration, which
were contrary to prior studies. We now show that these recent claims are not reproducible
and the reagents previously used to detect GDF11 are not GDF11 specific. We develop a
GDF11-specific immunoassay and show a trend toward increased GDF11 levels in sera of …
Summary
Age-related frailty may be due to decreased skeletal muscle regeneration. The role of TGF-β molecules myostatin and GDF11 in regeneration is unclear. Recent studies showed an age-related decrease in GDF11 and that GDF11 treatment improves muscle regeneration, which were contrary to prior studies. We now show that these recent claims are not reproducible and the reagents previously used to detect GDF11 are not GDF11 specific. We develop a GDF11-specific immunoassay and show a trend toward increased GDF11 levels in sera of aged rats and humans. GDF11 mRNA increases in rat muscle with age. Mechanistically, GDF11 and myostatin both induce SMAD2/3 phosphorylation, inhibit myoblast differentiation, and regulate identical downstream signaling. GDF11 significantly inhibited muscle regeneration and decreased satellite cell expansion in mice. Given early data in humans showing a trend for an age-related increase, GDF11 could be a target for pharmacologic blockade to treat age-related sarcopenia.
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