This one suggests that low-grade systemic inflammation promotes proteasome activity through activation of the NF-κB signaling and reduces the insulin-dependent anabolic potential in the aged human skeletal muscle.
Main findings:
Older adults with plasma hsCRP > 1 mg/L (defined as elevated systemic inflammation; ESI), but otherwise healthy demonstrate:
Older adults with plasma hsCRP > 1 mg/L (defined as elevated systemic inflammation; ESI), but otherwise healthy demonstrate:
i) increased proteasome activity, accompanied by increased protein carbonylation and IKKα/β phosphorylation.
- "Basal proteasome activity was found profoundly elevated in ESI compared to the control, and it was positively correlated with plasma hs-CRP levels...
"...This is consistent with the concentration-dependent protein degradation observed in differentiated myotubes following treatment with TNF-α, suggesting that the influence of chronic LGSI on proteasome activity is proportionate to the degree of inflammation...
"...We also observed increased muscle protein carbonylation and a greater amount of phosphorylated IKKα/β in ESI compared to control, both of which may explain the enhanced proteasome activity in ESI."
ii) reduced Pax7+ satellite cells
- "Τhis study shows that aged individuals with elevated plasma hs-CRP levels are characterized by lower SC content compared to their control counterparts...
"... At the same time, ESI displayed a greater CSA in type I fibers than control whereas CSA in type II fibers was comparable among groups. It appears, therefore, that the LGSI-associated reduction in SC pool during aging may be an early event preceding muscle atrophy."
iii) increased insulin resistance, at the basal state and impaired S6 ribosomal protein phosphorylation accompanied by hyperinsulinemia following an acute resistance exercise bout combined with protein ingestion.
"An intriguing finding of this investigation is that phosphorylation of rpS6 was substantially attenuated in ESI compared to control at 3 hours following RE and protein feeding....
"...rpS6 is one of the main substrates of ribosomal protein S6 kinase (S6K1), a downstream effector of mTOR, and its phosphorylation is inhibited following treatment with rapamycin (i.e. a potent mTORC1 inhibitor)...
"...thus suggesting that rpS6 phosphorylation status might be used as an indirect measure of the mTOR-S6K1 signaling axis activation...
"...Given that the latter is fundamental for contraction-induced stimulation of MPS following RE and that LGSI-driven insulin resistance is attributed to impaired activation of the IRS1-PI3K-PDK1-Akt signaling pathway...
"...we assume that the blunted rpS6 phosphorylation in ESI dictates reduced responsiveness of the PI3K/Akt/mTOR/S6K1 signal transduction pathway as a consequence of the coexistence of chronic LGSI and insulin resistance...
"...Actually, ESI displayed insulin resistance during the OGTT and increased insulinemia during the 3-hour postprandial period following RE...
"...Indeed, insulin resistance triggered by systemic inflammation has been implicated in the impaired activation of the PI3K/Akt/mTOR signaling pathway...
"...Furthermore, our observation that increased protein carbonylation in the basal state was accompanied by impaired rpS6 phosphorylation during the postprandial period following RE in ESI is consistent with the concept that elevated RONS production...
"...and consequently protein oxidation, not only affect proteasome-mediated proteolysis but also inhibit the activation of the Akt/mTOR signaling pathway, suggesting a redox-dependent regulation of the anabolic signaling in skeletal muscle...
"...Based on these findings, we propose that the coexistence of chronic LGSI-driven insulin resistance and protein oxidation contribute to the blunted stimulation of PI3K/Akt/mTOR/S6K1 signal transduction pathway, in the aged human skeletal muscle."
Low-Grade Systemic Inflammation Interferes with Anabolic and Catabolic Characteristics of the Aged Human Skeletal Muscle (open access)
doi.org/10.1155/2021/8…
#aging #Inflammation #InsulinResistance #exercise #TrainHard #GymLife #GymTime #muscle #strength #lift #GetStrong
doi.org/10.1155/2021/8…
#aging #Inflammation #InsulinResistance #exercise #TrainHard #GymLife #GymTime #muscle #strength #lift #GetStrong
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